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Sample records for dog mammary adenocarcinoma

  1. The antitumor effect of locoregional magnetic cobalt ferrite in dog mammary adenocarcinoma

    NASA Astrophysics Data System (ADS)

    Şincai, Mariana; Gângǎ, Diana; Bica, Doina; Vékás, Ladislau

    2001-01-01

    The endocytosis of nanosized magnetic particles by tumor cells led to numerous tests to establish the use of this phenomenon in antitumor therapy. The direct antitumor effect of a biocompatible cobalt-ferrite-based magnetic fluid directly inoculated in bitch mammary tumors was studied. A direct correlation between tumor cell lysis and cobalt ferrite was established in tumors. Massive endocytosis of magnetic particles was observed 1 h after the contact of magnetic fluid with tumor cells.

  2. Expression of prolactin receptors in normal canine mammary tissue, canine mammary adenomas and mammary adenocarcinomas

    PubMed Central

    2012-01-01

    Background Mammary tumors represent the most common neoplastic disease in female dogs. Recently, the promoting role of prolactin (PRL) in the development of human breast carcinoma has been shown. Possible proliferative, anti-apoptotic, migratory and angiogenic effects of PRL on human mammary cancer cells in vitro and in vivo were suggested. The effects of PRL are mediated by its receptor, and alterations in receptor expression are likely to play a role in tumor development. Currently, not much data is available about prolactin receptor (PRLR) expression in canine mammary tumors. To set the basis for investigations on the role of PRL in mammary tumorigenesis in this species, prolactin receptor expression was evaluated by semi-quantitative real time PCR and immunohistochemistry on 10 formalin-fixed, paraffin-embedded samples each of canine non-neoplastic mammary tissue, mammary adenomas and adenocarcinomas. Results The highest PRLR expression levels were found in normal mammary tissue, while adenomas, and to an even higher degree adenocarcinomas, showed a significant decrease in prolactin receptor expression. Compared to normal tissue, PRLR mRNA was reduced 2.4 fold (p = 0.0261) in adenomas and 4.8 fold (p = 0.008) in adenocarcinomas. PRLR mRNA expression was significantly lower in malignant than in benign lesions (p = 0.0165). Immunohistochemistry demonstrated PRLR expression in all three tissue types with signals mostly limited to epithelial cells. Conclusions Malignant transformation of mammary tissue was associated with a decline in prolactin receptor expression. Further studies are warranted to address the functional significance of this finding. PMID:22647582

  3. Urachal Adenocarcinoma in a Dog.

    PubMed

    Shrader, S; Lauridson, J; King, Z; Loch, J

    2016-05-01

    An 8-year-old neutered female Labrador retriever was presented with a 3-year history of intermittent haematuria. Ultrasonographic evaluation of the urinary bladder revealed a 2 × 3 × 0.5 cm intraluminal mass arising at the dome. The mass was excised via partial cystectomy. Histopathological examination revealed neoplastic epithelial cells arranged in sheets, irregularly-branching tubules and acini within a fibrovascular stroma. Neoplastic cells were cuboidal to polygonal with abundant foamy amphophilic cytoplasm, typically with a single, large, clear intracytoplasmic vacuole and eccentric nucleus ('signet ring' cells). Neoplastic tubules were often ectatic and contained abundant mucin. Immunohistochemically, the neoplastic cells had weak, cytoplasmic immunoreactivity for cytokeratin 7 and rare, but strong, nuclear immunoreactivity for CDX2. Based on the cellular morphology, immunolabelling characteristics and anatomical location, a diagnosis of adenocarcinoma of urachal origin was made. To the authors' knowledge, this is the first reported case of urachal adenocarcinoma in a dog. PMID:27009748

  4. Interaction of dimethylbenzanthracene and diethylstilbestrol on mammary adenocarcinoma formation in female ACI rats

    SciTech Connect

    Shellabarger, C.J.; McKnight, B.; Stone, J.P.; Holtzman, S.

    1980-06-01

    It has been reported that x-irradiation and diethylstilbestrol (DES) act synergistically on mammary adenocarcinoma formation in female ACI rats. The physical carcinogen, x-irradiation, was replaced by a chemical carcinogen, dimethylbenzanthracene (DMBA), and their interaction was studied in this system. Thirty-three female ACI rats were given 13.3 mg of DMBA per 100 grams of body weight. A total of 10 mammary adenocarcinomas were found, 8 in rats with a single mammary adenocarcinoma and 2 in a single rat, over a 266-day study period. Twenty-nine rats were implanted with a cholesterol pellet containing 5 mg of DES, and a total of 47 mammary adenocarcinomas were found, 5 in rats with a single mammary adenocarcinoma and 42 in 5 rats with 2 or more mammary adenocarcinomas. Twenty-four rats were given a combined treatment of both compounds, DES 2 days before DMBA, and a total of 126 mammary adenocarcinomas were found, 2 in rats with a single mammary adenocarcinoma and 124 in 18 rats with 2 or more mammary adenocarcinomas. The interaction between DMBA and DES was interpreted to be synergistic in regard to the proportion of rats with one or more mammary adenocarcinomas, and the median times of appearance of both first and second mammary adenocarcinomas. These interactions between DMBA and DES resemble the previously reported synergistic interactions between radiation and DES on mammary adenocarcinoma formation in female ACI rats.

  5. Tarantula cubensis extract alters the degree of apoptosis and mitosis in canine mammary adenocarcinomas.

    PubMed

    Gultiken, Nilgun; Guvenc, Tolga; Kaya, Duygu; Agaoglu, Ali Reha; Ay, Serhan Serhat; Kucukaslan, Ibrahim; Emre, Birten; Findik, Murat; Schäfer-Somi, Sabine; Aslan, Selim

    2015-01-01

    In the present study, 13 clinical cases of canine mammary adenocarcinoma were evaluated in order to understand the effect of Tarantula cubensis extract (TCE) on tumor tissue. Punch biopsies were taken from the tumors before treatment with TCE. Subcutaneous injections of TCE were administered three times at weekly intervals (3 mL per dog). Between days 7 and 10 after the third injection, the tumor masses were extirpated by complete unilateral mastectomy. Pre- and post-treatment tumor tissues were immunohistochemically assessed. The expression of B-cell lymphoma 2 (Bcl-2) was found to be higher in pre-treatment compared to post-treatment tissues (p < 0.01) whereas Ki-67 expression was lower in post-treatment tissues (p < 0.01). No significant differences in fibroblast growth factor or vascular endothelial growth factor expression were observed between pre- and post-treatment tissues (p > 0.05). The apoptotic index was determined to be low before treatment and increased during treatment. These results suggest that TCE may be effective for controlling the local growth of canine mammary adenocarcinoma by regulating apoptosis. PMID:25549212

  6. Tarantula cubensis extract alters the degree of apoptosis and mitosis in canine mammary adenocarcinomas

    PubMed Central

    Guvenc, Tolga; Kaya, Duygu; Agaoglu, Ali Reha; Ay, Serhan Serhat; Kucukaslan, Ibrahim; Emre, Birten; Findik, Murat; Schäfer-Somi, Sabine; Aslan, Selim

    2015-01-01

    In the present study, 13 clinical cases of canine mammary adenocarcinoma were evaluated in order to understand the effect of Tarantula cubensis extract (TCE) on tumor tissue. Punch biopsies were taken from the tumors before treatment with TCE. Subcutaneous injections of TCE were administered three times at weekly intervals (3 mL per dog). Between days 7 and 10 after the third injection, the tumor masses were extirpated by complete unilateral mastectomy. Pre- and post-treatment tumor tissues were immunohistochemically assessed. The expression of B-cell lymphoma 2 (Bcl-2) was found to be higher in pre-treatment compared to post-treatment tissues (p < 0.01) whereas Ki-67 expression was lower in post-treatment tissues (p < 0.01). No significant differences in fibroblast growth factor or vascular endothelial growth factor expression were observed between pre- and post-treatment tissues (p > 0.05). The apoptotic index was determined to be low before treatment and increased during treatment. These results suggest that TCE may be effective for controlling the local growth of canine mammary adenocarcinoma by regulating apoptosis. PMID:25549212

  7. Malignant mammary tumor in female dogs: environmental contaminants

    PubMed Central

    2010-01-01

    Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7%) as having complex carcinoma and three (33.3%) with simple carcinoma. From these tumors, seven (77.8%) presented aggressiveness degree III and two (22.2%) degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits. PMID:20587072

  8. Feline mammary adenocarcinoma: tumor size as a prognostic indicator

    PubMed Central

    Viste, Jodi R.; Myers, Sherry L.; Singh, Baljit; Simko, Elemir

    2002-01-01

    Mammary carcinomas and adenocarcinomas (MACs) are relatively common tumors in cats. The postexcisional survival period of affected cats is inversely proportional to tumor size, but the reported median survival periods for different tumor size categories is quite variable. This variability diminishes the prognostic value of reported data. In our study, cats with MACs greater than 3 cm in diameter had a 12-month median survival period, whereas those with MACs less than 3 cm in diameter had a 21-month survival period. Survival periods for cats with MACs smaller than 3 cm ranged from 3 to 54 months; therefore, tumor size alone is of limited prognostic value in cats with MACs smaller than 3 cm in diameter. In cats with MACs larger than 3 cm in diameter, tumor size appears to have much higher prognostic relevance, because this study, as well as others, have indicated that cats with MACs greater than 3 cm in diameter have a poor prognosis, with median survival periods ranging from 4 to 12 months. PMID:11802667

  9. Study of aggressiveness prediction of mammary adenocarcinoma by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Andrade Bitar, Renata; da Silva Martinho, Herculano; Zambelli Ramalho, Leandra Náira; dos Santos Junior, Arnaldo Rodrigues; Silva Ramalho, Fernando; Raniero, Leandro; Martin, Airton A.

    2012-01-01

    Although there are many articles focused on in vivo or ex vivo Raman analysis for cancer diagnosis, to the best of our knowledge its potential to predict the aggressiveness of tumor has not been fully explored yet. In this work Raman spectra in the finger print region of ex vivo breast tissues of both healthy mice (normal) and mice with induced mammary gland tumors (abnormal) were measured and associated to matrix metalloproteinase-19 (MMP-19) immunohistochemical exam. It was possible to verify that normal breast, benign lesions, and adenocarcinomas spectra, including the subtypes (cribriform, papillary and solid) could have their aggressiveness diagnosed by vibrational Raman bands. By using MMP- 19 exam it was possible to classify the samples by malignant graduation in accordance to the classification results of Principal Component Analysis (PCA). The spectra NM /MH were classified correctly in 100% of cases; CA/CPA group had 60 % of spectra correctly classified and for PA/AS 54% of the spectra were correctly classified.

  10. Mammary-like adenocarcinoma of the vulva associated to Paget's disease: a case report

    PubMed Central

    Meddeb, Sawsen; Rhim, Mohamed Salah; Mestiri, Sarra; Kouira, Mouna; Bibi, Mohamed; Khairi, Hedi; Yacoubi, Mohamed Tahar

    2014-01-01

    Mammary-like adenocarcinoma of the vulva associated to Paget's disease is exceedingly rare. So, it is very important to perform all the pathological and immunohistochemical investigations to achieve differential diagnosis from both a metastatic lesion from an orthotopic breast cancer and a vulvar adnexal tumor. This report describes a case of vulvar Paget's disease associated with underlying mammary-like adenocarcinoma diagnosed in the Department of Obstetrics and Gynecology of Farhat Hached university hospital of Sousse in Tunisia. We also review previously reported cases of primary breast-like carcinoma of the vulva with or without Paget's disease. PMID:25848451

  11. Effect of spaying and timing of spaying on survival of dogs with mammary carcinoma.

    PubMed

    Sorenmo, K U; Shofer, F S; Goldschmidt, M H

    2000-01-01

    The risk of developing mammary gland tumors in dogs is significantly decreased by ovariohysterectomy at an early age. However, previous studies have not found a benefit to ovariohysterectomy concurrent with tumor removal in dogs with established mammary gland tumors, suggesting that the progression of these tumors is independent of continued estrogen stimulation. The purpose of this study was to evaluate the effect of spaying and of the timing of spaying on survival in dogs with mammary gland carcinoma. Signalment, spay status and spay age, tumor characteristics, treatment. survival, and cause of death of 137 dogs with mammary gland carcinoma were analyzed. The dogs were classified into 3 groups according to spay status and spay time: intact dogs, dogs spayed less than 2 years before tumor surgery (SPAY 1), and dogs spayed more than 2 years before their tumor surgery (SPAY 2). Dogs in the SPAY 1 group lived significantly longer than dogs in SPAY 2 and intact dogs (median survival of 755 days, versus 301 and 286 days, respectively, P = .02 and .03). After adjusting for differences between the spay groups with regard to age, histologic differentiation, and vascular invasion, SPAY 1 dogs survived 45% longer compared to dogs that were either intact or in the SPAY 2 group (RR = .55; 95% CI .32-.93; P = .03). This study reveals ovariohysterectomy to be an effective adjunct to tumor removal in dogs with mammary gland carcinoma and that the timing of ovariohysterectomy is important in influencing survival. PMID:10830539

  12. Surgical removal of a mammary adenocarcinoma and a granulosa cell tumor in an African pygmy hedgehog

    PubMed Central

    Wellehan, James F.X.; Southorn, Erin; Smith, Dale A.; Taylor, Michael

    2003-01-01

    A 3-year-old, female African pygmy hedgehog (Atelerix albiventris) was referred with a history of hematuria. Hyperglycemia and glucosuria were found at presentation. Mammary adenocarcinoma and a granulosa cell tumor were found and removed surgically. Glucosuria and hematuria resolved, and the hedgehog has done well for 10 mo postoperatively. PMID:12677695

  13. Surgical removal of a mammary adenocarcinoma and a granulosa cell tumor in an African pygmy hedgehog.

    PubMed

    Wellehan, James F X; Southorn, Erin; Smith, Dale A; Taylor, W Michael

    2003-03-01

    A 3-year-old, female African pygmy hedgehog (Atelerix albiventris) was referred with a history of hematuria. Hyperglycemia and glucosuria were found at presentation. Mammary adenocarcinoma and a granulosa cell tumor were found and removed surgically. Glucosuria and hematuria resolved, and the hedgehog has done well for 10 mo postoperatively. PMID:12677695

  14. Pleural effusion secondary to thoracic metastatic mammary adenocarcinoma in a mare.

    PubMed

    Foreman, J H; Weidner, J P; Parry, B W; Hargis, A

    1990-11-01

    A 17-year-old Quarter Horse mare was examined nearly 3 years after excision and cryotherapy of a papillary mammary gland adenocarcinoma. The mare had been used for pleasure riding since surgery, but had recently developed progressive dyspnea. The mare had clinical evidence of pleural effusion, but died before further clinical examination and treatment were instituted. Necropsy revealed deep mammary masses with similar nodules in the deep inguinal, renal, and mediastinal lymph nodes and in the lungs, pericardium, visceral and parietal pleurae, and left ovary. The masses were identified as papillary mammary gland adenocarcinoma. Large volumes of free pleural and peritoneal fluid were detected. The pleural fluid contained similar neoplastic cells that could have been readily detected by exfoliative cytologic examination had the mare survived. PMID:2254151

  15. Identification of microfilaria in a mammary mass aspirate from a female dog.

    PubMed

    Burgess, Hilary J; Wagner, Brent

    2016-04-01

    A filarial nematode larva (microfilaria) was found in an aspirate of a mammary mass from a dog imported to Saskatchewan from Myanmar. This was an unusual location for a microfilaria and numerous filarial nematodes infecting dogs in Asia had to be considered. This report describes the laboratory diagnosis of canine heartworm disease in this dog. PMID:27041753

  16. Ultrasound and multidetector computed tomography of mandibular salivary gland adenocarcinoma in two dogs

    PubMed Central

    Lenoci, D.; Ricciardi, M.

    2015-01-01

    Malignant tumors of the salivary glands are rare in dogs, with adenocarcinoma being the most represented. Parotid and mandibular glands are most commonly affected in dogs. Because of local invasivity and high metastatic potential, preoperative imaging evaluation of mandibular region and tumoral staging is essential along with biopsy sampling. The present manuscript describes the ultrasound and computed tomographic imaging findings of mandibular gland adenocarcinoma in two dogs and discusses their clinical utility. PMID:26753133

  17. Survey radiography and computerized tomography imaging of the thorax in female dogs with mammary tumors

    PubMed Central

    2010-01-01

    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. PMID:20214816

  18. Inflammatory mammary carcinoma in 12 dogs: Clinical features, cyclooxygenase-2 expression, and response to piroxicam treatment

    PubMed Central

    de M. Souza, Carlos H.; Toledo-Piza, Evandro; Amorin, Renee; Barboza, Andrigo; Tobias, Karen M.

    2009-01-01

    Canine inflammatory mammary carcinoma (IMC) is a rare, locally aggressive, highly metastatic tumor that is poorly responsive to treatment. The purposes of this study were to retrospectively evaluate the history, signalment, and clinical signs of dogs with IMC; compare the outcome of affected dogs treated with traditional chemotherapy with those treated with piroxicam; evaluate Cox-2 expression of IMC cells; and correlate Cox-2 expression with outcome based on treatment. Strong cyclooxygenase-2 expression was present in all tumors. Improvement in clinical condition and disease stability was achieved in all dogs treated with piroxicam, with mean and median progression-free survival of 171 and 183 days, respectively. Median survival time of 3 dogs treated with doxorubicin-based protocols was 7 days, which was significantly less than that of dogs treated with piroxicam (median, 185 days). In conclusion, piroxicam should be considered as a single agent for the treatment of dogs with inflammatory mammary carcinoma. PMID:19436636

  19. Iridociliary adenocarcinoma with oncocytic change in a dog.

    PubMed

    Okawauchi, Mitsuteru; Tsuboi, Masaya; Nibe, Kazumi; Nagamine, Eiji; Iwane, Hideaki; Uchida, Kazuyuki

    2016-06-01

    An intraocular mass lesion was found in the left eyeball in a spayed female Pembroke Welsh Corgi dog. The surgically resected left eyeball was pathologically examined. Histologically, the mass lesion consisted of proliferation of the atypical cuboidal or columnar epithelial cells, arranging in papillary, tubular or solid form. In addition, some neoplastic cells showed oncocytic change characterized as large oval cells with numerous eosinophilic intracytoplasmic granules. Cytoplasm of the oncocytic cells showed dark blue granules by phosphotungstic acid-hematoxylin stain. Immunohistochemically, the oncocytic cells were intensely positive for cytochrome C. Based on these findings, the ocular mass was diagnosed as iridociliary adenocarcinoma with oncocytic change. The findings indicate that the oncocytic changes of the neoplastic epithelial cells might be caused by mitochondrial accumulation. PMID:26822120

  20. Iridociliary adenocarcinoma with oncocytic change in a dog

    PubMed Central

    OKAWAUCHI, Mitsuteru; TSUBOI, Masaya; NIBE, Kazumi; NAGAMINE, Eiji; IWANE, Hideaki; UCHIDA, Kazuyuki

    2016-01-01

    An intraocular mass lesion was found in the left eyeball in a spayed female Pembroke Welsh Corgi dog. The surgically resected left eyeball was pathologically examined. Histologically, the mass lesion consisted of proliferation of the atypical cuboidal or columnar epithelial cells, arranging in papillary, tubular or solid form. In addition, some neoplastic cells showed oncocytic change characterized as large oval cells with numerous eosinophilic intracytoplasmic granules. Cytoplasm of the oncocytic cells showed dark blue granules by phosphotungstic acid-hematoxylin stain. Immunohistochemically, the oncocytic cells were intensely positive for cytochrome C. Based on these findings, the ocular mass was diagnosed as iridociliary adenocarcinoma with oncocytic change. The findings indicate that the oncocytic changes of the neoplastic epithelial cells might be caused by mitochondrial accumulation. PMID:26822120

  1. A recurrent marker chromosome involving chromosome 1 in two mammary tumors of the dog.

    PubMed

    Bartnitzke, S; Motzko, H; Caselitz, J; Kornberg, M; Bullerdiek, J; Schloot, W

    1992-01-01

    An apparently identical marker chromosome resulting from a chromosome 1. translocation was found in the mammary carcinomas of two bitches. Although these karyotypic aberrations were the sole clonal aberrations detected, it was not possible to unambiguously identify the material translocated to the chromosome 1 in either animal. Our observations, however, represent the first report of a recurring marker chromosome in mammary tumors of the dog and suggest that these tumors may become an interesting model for human breast cancer. PMID:1319309

  2. A mammary adenocarcinoma murine model suitable for the study of cancer immunoediting

    PubMed Central

    2014-01-01

    Background Cancer immunoediting is a dynamic process composed of three phases: elimination (EL), equilibrium (EQ) and escape (ES) that encompasses the potential host-protective and tumor-sculpting functions of the immune system throughout tumor development. Animal models are useful tools for studying diseases such as cancer. The present study was designed to characterize the interaction between mammary adenocarcinoma M-406 and CBi, CBi− and CBi/L inbred mice lines. Results The mammary adenocarcinoma M-406 developed spontaneously in a CBi mouse. CBi/L and CBi− mice were artificially selected for body conformation from CBi. When CBi mice are s.c. challenged with M-406, tumor growths exponentially in 100% of animals, while in CBi− the tumor growths briefly and then begins a rejection process in 100% of the animals. In CBi/L the growth of the tumor shows the three phases: 51.6% in ES, 18.5% in EQ and 29.8% in EL. Conclusions The results obtained support the conclusion that the system M-406 plus the inbred mouse lines CBi, CBi− and CBi/L, is a good murine model to study the process of tumor immunoediting. PMID:24885995

  3. Surgical treatment of mammary carcinomas in dogs with or without postoperative chemotherapy.

    PubMed

    Tran, C M; Moore, A S; Frimberger, A E

    2016-09-01

    This retrospective study identified prognostic factors associated with survival; and compared survival data in 94 canine mammary carcinoma (MCA) dogs treated with surgery (n = 58), or surgery and adjunct chemotherapy (n = 36), and a subset of dogs with poor prognostic factors. On multivariate analysis independent predictors of median survival time (MST) were clinical stage, lymphatic invasion (LI; present 179 days; none 1098 days), ulceration (present 118 days; none 443 days) and surgical margins (incomplete 70 days; complete 872 days). Complete surgical margins were associated with MST in dogs with stages 1-3 MCA (incomplete 68 days; complete 1098 days) and dogs with LI (incomplete 70 days; complete 347 days). There was no statistically significant improvement in MST in dogs with advanced disease (stage 4 or LI) treated with adjunctive chemotherapy (chemotherapy 228 days; none 194 days); although five dogs with complete surgical margins that received mitoxantrone and carboplatin had a mean survival of 1139 days. PMID:24735412

  4. Oxidative stress and inflammatory response biomarkers in dogs with mammary carcinoma.

    PubMed

    Machado, Vanessa S; Crivellenti, Leandro Z; Bottari, Nathieli B; Tonin, Alexandre A; Pelinson, Luana P; Borin-Crivellenti, Sofia; Santana, Aureo E; Torbitz, Vanessa D; Moresco, Rafael N; Duarte, Thiago; Duarte, Marta M M F; Schetinger, Maria Rosa C; Morsch, Vera M; Jaques, Jeandre A; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

    2015-09-01

    Mammary carcinoma is the most common cancer that affects dogs, and in many cases it leads to death. Thus, given the importance of this disease, to clarify its pathogenesis is an important measure. In this sense, the aim of this study was to investigate the levels of cytokines and nitric oxide (NO), oxidative and antioxidant status, as well as the activity of adenosine deaminase (ADA) and butyrylcholinesterase (BChE) in dogs diagnosed with mammary carcinoma. With this purpose, thirty-three (33) serum samples from female dogs with histopathological diagnosis of mammary carcinoma, without evidence of metastasis, were used (group B). The material was classified based on the degree of malignancy, as follows: subgroup B1 (low-grade malignancy; n=26) and subgroup B2 (high grade of malignancy; n=7). Serum samples from healthy females (group A; n=10) were used as negative control. Our results showed that levels of cytokines (TNF-α, INF-γ, IL-1, and IL-6), NOx (nitrite/nitrate), AOPP (protein oxidation), and FRAP (antioxidant power) were significantly (P<0.05) increased in dogs with mammary carcinoma (group B), when compared with group A. On the other hand, ADA activity was significantly decreased (P<0.05) in both subgroups B1 and B2, when compared with group A. BChE activity, however, was reduced (P<0.05) only in subgroup B2 when compared with group A and subgroup B1. Unlike other variables, NO, AOPP, and IFN-γ were influenced by the degree of tumor malignancy, i.e., their levels were even higher in subgroup B2. Therefore, based on these results, we can conclude that all variables investigated are related to the pathogenesis of this disease, since they were altered in dogs with mammary tumor. Additionally, we suggest that ADA activity had an anti-inflammatory effect on these tumor samples, probably in order to modulate the inflammatory response. PMID:26166177

  5. Development of dog mammary tumor xenograft in immunosuppressed Swiss albino mice.

    PubMed

    Rajmani, R S; Singh, Prafull Kumar; Kumar, Sanjay; Kumar, G Ravi; Sahoo, Aditya P; Santra, Lakshman; Saxena, Shikha; Singh, Lakshya Veer; Chaturvedi, Uttara; Saxena, Lovleen; Desai, G S; Gupta, Shishir Kumar; Kumar, Amit; Jadon, N S; Tiwari, Ashok K

    2014-10-01

    Development and study of dog mammary tumour xenograft in immunosuppressed Swiss Albino Mice adds a new dimension in cancer research as dog tumors have many similarities with human tumors regarding progression, histopathology, molecular mechanism, immune response and therapy. Failure of the immune system to recognize and eliminate cancer cells leads to cancer progression and the fight between immune cells and cancer cells has a great role in understanding the mechanism of cancer progression and elimination. Rejection and acceptance of tumour xenograft depends on efficiency of CD4+, CD8+ and NK cell populations. In the present investigation, dog mammary tumor xenograft in cyclosporine-A and gamma-irradiated, immunosuppressed Swiss Albino mice was developed and the immune cell status of graft accepted and rejected mice was assessed. It was observed that all the major immune cells (CD4+, CD8+ and NK cells) play an equal role in tumour rejection. PMID:25345242

  6. In vivo diagnosis of mammary adenocarcinoma using Raman spectroscopy: an animal model study

    NASA Astrophysics Data System (ADS)

    Bitar, R. A.; Ribeiro, D. G.; dos Santos, E. A. P.; Ramalho, L. N. Z.; Ramalho, F. S.; Martin, A. A.; Martinho, H. S.

    2010-02-01

    Breast cancer is the most frequent cancer type in women Worldwide. Sensitivity and specificity of clinical breast examinations have been estimated from clinical trials to be approximately 54 % and 94 %, respectively. Further, approximately 95 % of all positive breast cancer screenings turn out to be false-positive. The optimal method for early detection should be both highly sensitive to ensure that all cancers are detected, and also highly specific to avoid the humanistic and economic costs associated with false-positive results. In vivo optical spectroscopy techniques, Raman in particular, have been pointed out as promising tools to improve the accuracy of screening mammography. The aim of the present study was to apply FT-Raman spectroscopy to discriminate normal and adenocarcinoma breast tissues of Sprague-Dawley female rats. The study was performed on 32 rats divided in the control (N=5) and experimental (N=27) groups. Histological analysis indicated that mammary hyperplasia, cribriform, papillary and solid adenocarcinomas were found in the experimental group subjects. The spectral collection was made using a commercial FT-Raman Spectrometer (Bruker RFS100) equipped with fiber-optic probe (RamProbe) and the spectral region between 900 and 1800 cm-1 was analyzed. Principal Components Analysis, Cluster Analysis, and Linear Discriminant Analysis with cross-validation were applied as spectral classification algorithm. As concluding remarks it is show that normal and adenocarcinoma tissues discriminations was possible (correct proportion for Transcutaneous collection mode was 80.80% and for "Open Sky" mode was 91.70%); however, a conclusive diagnosis among the four lesion subtypes was not possible.

  7. Mucinous Pleural Effusion in a Dog with a Pulmonary Adenocarcinoma and Carcinomatosis.

    PubMed

    Tropf, Melissa; Sellon, Rance; Paulson, Kathleen; Nelson, Danielle

    2015-01-01

    An 11 yr old castrated male greyhound presented to the Washington State University's Veterinary Teaching Hospital (WSU VTH) for evaluation of a 4 day history of pleural effusion. The pleural effusion had a gelatinous appearance, suggestive of mucus, and was characterized cytologically as a pyogranulomatous exudate with some features suggestive of a carcinoma. Postmortem examination identified a pulmonary mass with evidence of carcinomatosis. Pulmonary papillary adenocarcinoma with carcinomatosis was the histologic diagnosis. Abundant mucin production was present, consistent with a mucinous pulmonary adenocarcinoma. To the authors' knowledge, this is the first report of a mucinous pulmonary adenocarcinoma with mucus pleural effusion in a dog. PMID:26355581

  8. Neuroendocrine carcinoma of the mammary gland in a dog.

    PubMed

    Nakahira, R; Michishita, M; Yoshimura, H; Hatakeyama, H; Takahashi, K

    2015-01-01

    A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small, round hypochromatic nuclei and abundant cytoplasm. Metastases were observed in the inguinal lymph node. Immunohistochemically, most tumour cells expressed cytokeratin (CK) 20, chromogranin A, neuron-specific enolase, synaptophysin and oestrogen receptor-β, but not low molecular weight CK (CAM5.2), p63 and insulin. Ultrastructurally, the tumour cells contained a large number of electron-dense granules corresponding to neuroendocrine granules. Based on these findings, this case was diagnosed as a neuroendocrine carcinoma of the mammary gland. PMID:25670668

  9. In-vitro depth-dependent hyperthermia of human mammary gland adenocarcinoma.

    PubMed

    Dunn, Andrew W; Zhang, Yu; Mast, David; Pauletti, Giovanni M; Xu, Hong; Zhang, Jiaming; Ewing, Rodney C; Shi, Donglu

    2016-12-01

    Nanoparticle mediated photothermal ablation of cancerous tissue shows promising results and applicability as a highly efficacious treatment method. As a majority of the photothermal work has been conducted with minimal attenuation of the laser before reaching the nanoparticles within surface seeded tumors in-vivo or through buffered media in-vitro, it is important to understand the effects of greater laser attenuation on photothermal efficacy mediated by changes in the scattering and absorption of the laser. Photothermal efficacy using a near infrared (NIR) 785nm laser irradiating polystyrene (PS) stabilized magnetite (Fe3O4) nanoparticles (PS-Fe3O4) is examined on MDA-MB-231 human mammary gland adenocarcinoma in-vitro. Agarose gel columns of various heights were created to simulate soft tissue and subsequently used for NIR laser attenuation. Polystyrene was found to significantly improve magnetite nanoparticle stability in serum containing media and modified Hank's Balanced Salt Solution and was able to induce significant hyperthermic ablation at mass concentrations which also did not elicit significant innate toxicity. Furthermore it was found that the polystyrene coating significantly reduced innate toxicity over 48h compared to uncoated magnetite. Agar gel layers provided similar optical attenuation in the NIR region to skin and prostate. PMID:27612683

  10. Expression of hypoxia-inducible factor-1α and vascular density in mammary adenomas and adenocarcinomas in bitches

    PubMed Central

    2013-01-01

    Background The study aimed at examining hypoxia-inducible factor (HIF)1α expression in adenocarcinomas and adenomas in bitches in regard to tumour malignancy grade, proliferation, apoptosis and vascularisation. Therefore, paraffin sections of 15 adenomas and 64 adenocarcinomas sampled from 79 dogs aged 6 to 16 years were analysed. Results A significantly higher HIF-1α expression was noted in adenocarcinomas in comparison to adenomas (P < 0.0004). Moreover, HIF-1α expression in adenocarcinomas correlated positively with tumour malignancy grade (r = 0.59, P < 0.05), Ki-67 antigen expression (r = 0.43; P < 0.0005), TUNEL-positive cells (r = 0.62, P < 0001) and tumour vascularity measured by quantification of vessels characterized by the expression of von Willebrand Factor (r = 0.57, P < 0.05). Conclusion Results of this study indicate a similar biological role of HIF-1α in dogs and in humans, which may confirm suitability of the animal model in investigations on progression of tumours in humans. PMID:24153191

  11. Characterization of mammary adenocarcinomas in male rats after N-methyl-N-nitrosourea exposure-Potential for human male breast cancer model.

    PubMed

    Yoshizawa, Katsuhiko; Yuki, Michiko; Kinoshita, Yuichi; Emoto, Yuko; Yuri, Takashi; Shikata, Nobuaki; Elmore, Susan A; Tsubura, Airo

    2016-05-01

    The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor α (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans. PMID:26852374

  12. Occurrence of Leishmania infantum and associated histological alterations in the genital tract and mammary glands of naturally infected dogs.

    PubMed

    Boechat, Viviane Cardoso; Mendes Junior, Artur Augusto Velho; Madeira, Maria de Fátima; Ferreira, Luiz Claudio; Figueiredo, Fabiano Borges; Rodrigues, Francisco das Chagas de Carvalho; Oliveira, Valéria da Costa; de Oliveira, Raquel de Vasconcellos Carvalhaes; Menezes, Rodrigo Caldas

    2016-06-01

    The objectives of this study were to evaluate the occurrence of Leishmania infantum in the male and female genital tract and female mammary glands of dogs and the parasite burden and to identify histological alterations associated with this protozoan. Twenty male and 20 female Leishmania-seropositive dogs with isolation of L. infantum were examined. Tissue samples of the prepuce, glans, epididymis, testes, prostate, vulva, vagina, uterus, uterine tubes, and mammary glands were analyzed by immunohistochemistry and histopathology. For parasitological culture and in situ hybridization, samples were collected from the testis, epididymis, and uterus. Additionally, seminal fluid was aspirated from the epididymis for parasitological culture. In the genital tract, 34 (85 %) dogs, including 18 males and 16 females, were positive for Leishmania. Of these, 27 (79 %) animals were symptomatic. Leishmania was detected in the mammary glands of 13 (65 %) females. L. infantum was isolated for the first time from the seminal fluid and uterus of naturally infected dogs. The parasite burden and intensity of the inflammatory reaction were greater in the prepuce and glans of males and in the vulva and mammary glands of females. In addition to inflammation, testicular degeneration, atrophy, absence of spermatogenesis, and necrosis were observed. Detection of amastigote forms in the mammary gland lumen indicates possible elimination of this parasite in milk. The frequent parasitism observed in the genital tract of infected males and females and the viability of L. infantum in seminal fluid and uterus suggest the possibility of bidirectional venereal and vertical transmission. PMID:26979730

  13. Multiple Delivery of siRNA against Endoglin into Murine Mammary Adenocarcinoma Prevents Angiogenesis and Delays Tumor Growth

    PubMed Central

    Dolinsek, Tanja; Markelc, Bostjan; Sersa, Gregor; Coer, Andrej; Stimac, Monika; Lavrencak, Jaka; Brozic, Andreja; Kranjc, Simona; Cemazar, Maja

    2013-01-01

    Endoglin is a transforming growth factor-β (TGF- β) co-receptor that participates in the activation of a signaling pathway that mediates endothelial cell proliferation and migration in angiogenic tumor vasculature. Therefore, silencing of endoglin expression is an attractive approach for antiangiogenic therapy of tumors. The aim of our study was to evaluate the therapeutic potential of small interfering RNA (siRNA) molecules against endoglin in vitro and in vivo. Therapeutic potential in vitro was assessed in human and murine endothelial cells (HMEC-1, 2H11) by determining endoglin expression level, cell proliferation and tube formation. In vivo, the therapeutic potential of siRNA molecules was evaluated in TS/A mammary adenocarcinoma growing in BALB/c mice. Results of our study showed that siRNA molecules against endoglin have a good antiangiogenic therapeutic potential in vitro, as expression of endoglin mRNA and protein levels in mouse and human microvascular endothelial cells after lipofection were efficiently reduced, which resulted in the inhibition of endothelial cell proliferation and tube formation. In vivo, silencing of endoglin with triple electrotransfer of siRNA molecules into TS/A mammary adenocarcinoma also significantly reduced the mRNA levels, number of tumor blood vessels and the growth of tumors. The obtained results demonstrate that silencing of endoglin is a promising antiangiogenic therapy of tumors that could not be used as single treatment, but as an adjunct to the established cytotoxic treatment approaches. PMID:23593103

  14. Pilot study of p62 DNA vaccine in dogs with mammary tumors.

    PubMed

    Gabai, Vladimir; Venanzi, Franco M; Bagashova, Elena; Rud, Oksana; Mariotti, Francesca; Vullo, Cecilia; Catone, Giuseppe; Sherman, Michael Y; Concetti, Antonio; Chursov, Andrey; Latanova, Anastasia; Shcherbinina, Vita; Shifrin, Victor; Shneider, Alexander

    2014-12-30

    Our previous data demonstrated profound anti-tumor and anti-metastatic effects of p62 (sqstm1) DNA vaccine in rodents with various types of transplantable tumors. Testing anti-cancer medicine in dogs as an intermediary step of translational research program provides two major benefits. First, clinical data collected in target animals is required for FDA/USDA approval as a veterinary anti-cancer drug or vaccine. It is noteworthy that the veterinary community is in need of novel medicine for the prevention and treatment of canine and feline cancers. The second more important benefit of testing anti-cancer vaccines in dogs is that spontaneous tumors in dogs may provide invaluable information for human trials. Here, we evaluated the effect(s) of p62 DNA vaccine on mammary tumors of dogs. We found that p62 DNA vaccine administered i.m. decreased or stabilized growth of locally advanced lesions in absence of its overall toxic effects. The observed antitumor activity was associated with lymphocyte infiltration and tumor encapsulation via fibrotic reaction. This data justifies both human clinical trials and veterinary application of p62 DNA vaccine. PMID:25296974

  15. Pilot study of p62 DNA vaccine in dogs with mammary tumors

    PubMed Central

    Bagashova, Elena; Rud, Oksana; Mariotti, Francesca; Vullo, Cecilia; Catone, Giuseppe; Sherman, Michael Y.; Concetti, Antonio; Chursov, Andrey; Latanova, Anastasia; Shcherbinina, Vita; Shneider, Alexander

    2014-01-01

    Our previous data demonstrated profound anti-tumor and anti-metastatic effects of p62 (sqstm1) DNA vaccine in rodents with various types of transplantable tumors. Testing anti-cancer medicine in dogs as an intermediary step of translational research program provides two major benefits. First, clinical data collected in target animals is required for FDA/USDA approval as a veterinary anti-cancer drug or vaccine. It is noteworthy that the veterinary community is in need of novel medicine for the prevention and treatment of canine and feline cancers. The second more important benefit of testing anti-cancer vaccines in dogs is that spontaneous tumors in dogs may provide invaluable information for human trials. Here, we evaluated the effect(s) of p62 DNA vaccine on mammary tumors of dogs. We found that p62 DNA vaccine administered i.m. decreased or stabilized growth of locally advanced lesions in absence of its overall toxic effects. The observed antitumor activity was associated with lymphocyte infiltration and tumor encapsulation via fibrotic reaction. This data justifies both human clinical trials and veterinary application of p62 DNA vaccine. PMID:25296974

  16. Breed variations in the incidence of pyometra and mammary tumours in Swedish dogs.

    PubMed

    Jitpean, S; Hagman, R; Ström Holst, B; Höglund, O V; Pettersson, A; Egenvall, A

    2012-12-01

    Dogs enrolled in a Swedish insurance company (during 1995-2006) were studied for development of pyometra and mammary tumours (MTs), with special attention to breed and age. There were over 260,000 female dogs with over 1,000,000 dog-years at risk (DYAR) in the database, using data on bitches up to 10 years of age and 110 breeds with over 1000 DYAR. In total, 20 423 bitches were diagnosed with pyometra and 11,758 with MTs and 30,131 with either or both of the two diseases. The incidence rate (IR) for pyometra was 199 (95% CI 196-202), for MTs 112 (95% CI 110-114) and for either or both of the two diseases 297 (95% CI 294-301) dogs per 10,000 DYAR. The mean age of diagnosis pyometra was 7.0 years (SD ± 2.2), MTs 8.0 years (SD ± 1.6). In all breeds, the overall proportion of the bitches that developed disease by 10 years of age was for pyometra 19%, MTs 13%, and either or both of two diseases 30%. The top 10 breeds diagnosed with either or both of the two diseases were the Leonberger (73%), Irish Wolfhound (69%), Bernese Mountain Dog (69%), Great Dane (68%), Staffordshire Bull Terrier (66%), Rottweiler (65%), Bullterrier (62%), Doberman (62%), Bouvier des Flandres (60%), Airdaleterrier (60%). These data provide information of the combined disease incidence in a large number of different breeds. Breed variations in incidence rate suggests genetic components in disease development. Our study may be valuable in the search for genetic risk-factors or protective factors. PMID:23279535

  17. Epidemiological Study of Mammary Tumors in Female Dogs Diagnosed during the Period 2002-2012: A Growing Animal Health Problem

    PubMed Central

    Salas, Yaritza; Márquez, Adelys; Diaz, Daniel; Romero, Laura

    2015-01-01

    Epidemiological studies enable us to analyze disease behavior, define risk factors and establish fundamental prognostic criteria, with the purpose of studying different types of diseases. The aim of this study was to determine the epidemiological characteristics of canine mammary tumors diagnosed during the period 2002-2012. The study was based on a retrospective study consisting of 1,917 biopsies of intact dogs that presented mammary gland lesions. Biopsies were sent to the Department of Pathology FMVZ-UNAM diagnostic service. The annual incidence of mammary tumors was 16.8%: 47.7% (benign) and 47.5% (malignant). The highest number of cases was epithelial, followed by mixed tumors. The most commonly diagnosed tumors were tubular adenoma, papillary adenoma, tubular carcinoma, papillary carcinoma, solid carcinoma, complex carcinoma and carcinosarcoma. Pure breeds accounted for 80% of submissions, and the Poodle, Cocker Spaniel and German Shepherd were consistently affected. Adult female dogs (9 to 12 years old) were most frequently involved, followed by 5- to 8-year-old females. Some association between breeds with histological types of malignant tumors was observed, but no association was found between breeds and BN. Mammary tumors in intact dogs had a high incidence. Benign and malignant tumors had similar frequencies, with an increase in malignant tumors in the past four years of the study. Epithelial tumors were more common, and the most affected were old adult females, purebreds and small-sized dogs. Mammary tumors in dogs are an important animal health problem that needs to be solved by improving veterinary oncology services in Mexico. PMID:25992997

  18. Epidemiological Study of Mammary Tumors in Female Dogs Diagnosed during the Period 2002-2012: A Growing Animal Health Problem.

    PubMed

    Salas, Yaritza; Márquez, Adelys; Diaz, Daniel; Romero, Laura

    2015-01-01

    Epidemiological studies enable us to analyze disease behavior, define risk factors and establish fundamental prognostic criteria, with the purpose of studying different types of diseases. The aim of this study was to determine the epidemiological characteristics of canine mammary tumors diagnosed during the period 2002-2012. The study was based on a retrospective study consisting of 1,917 biopsies of intact dogs that presented mammary gland lesions. Biopsies were sent to the Department of Pathology FMVZ-UNAM diagnostic service. The annual incidence of mammary tumors was 16.8%: 47.7% (benign) and 47.5% (malignant). The highest number of cases was epithelial, followed by mixed tumors. The most commonly diagnosed tumors were tubular adenoma, papillary adenoma, tubular carcinoma, papillary carcinoma, solid carcinoma, complex carcinoma and carcinosarcoma. Pure breeds accounted for 80% of submissions, and the Poodle, Cocker Spaniel and German Shepherd were consistently affected. Adult female dogs (9 to 12 years old) were most frequently involved, followed by 5- to 8-year-old females. Some association between breeds with histological types of malignant tumors was observed, but no association was found between breeds and BN. Mammary tumors in intact dogs had a high incidence. Benign and malignant tumors had similar frequencies, with an increase in malignant tumors in the past four years of the study. Epithelial tumors were more common, and the most affected were old adult females, purebreds and small-sized dogs. Mammary tumors in dogs are an important animal health problem that needs to be solved by improving veterinary oncology services in Mexico. PMID:25992997

  19. Extramedullary hematopoiesis in a case of benign mixed mammary tumor in a female dog: cytological and histopathological assessment

    PubMed Central

    2010-01-01

    Backgroud Extramedullary hematopoiesis (EMH) is defined as the presence of hematopoietic stem cells such as erythroid and myeloid lineage plus megakaryocytes in extramedullary sites like liver, spleen and lymph nodes and is usually associated with either bone marrow or hematological disorders. Mammary EMH is a rare condition either in human and veterinary medicine and can be associated with benign mixed mammary tumors, similarly to that described in this case. Case presentation Hematopoietic stem cells were found in a benign mixed mammary tumor of a 7-year-old female mongrel dog that presents a nodule in the left inguinal mammary gland. The patient did not have any hematological abnormalities. Cytological evaluation demonstrated two distinct cell populations, composed of either epithelial or mesenchymal cells, sometimes associated with a fibrillar acidophilic matrix, apart from megakaryocytes, osteoclasts, metarubricytes, prorubricytes, rubricytes, rubriblasts, promyelocytes, myeloblasts. Histological examination confirmed the presence of an active hematopoietic bone marrow within the bone tissue of a benign mammary mixed tumor. Conclusions EMH is a rare condition described in veterinary medicine that can be associated with mammary mixed tumors. It's detection can be associated with several neoplastic and non-neoplastic mammary lesions, i.e. osteosarcomas, mixed tumors and bone metaplasia. PMID:20846427

  20. A case of gastric adenocarcinoma in a Shih Tzu dog: successful treatment of early gastric cancer.

    PubMed

    Lee, Hee-Chun; Kim, Ji-Hyun; Jee, Cho-Hee; Lee, Jae-Hoon; Moon, Jong-Hyun; Kim, Na-Hyun; Sur, Jung-Hyang; Cho, Kyu-Woan; Kang, Byeong-Teck; Ha, Jeongim; Jung, Dong-In

    2014-07-01

    A 9-year-old castrated male Shih Tzu dog was referred to us, because of chronic vomiting. The patient's hematological, radiographic, ultrasonographic, endoscopic and histological examinations were evaluated for diagnosis. Hematologic analysis indicated moderate anemia and azotemia. Based on the imaging studies, an oval-shaped mass was identified in the gastric pylorus area. A proliferative mass was found on endoscopic examination, and we performed biopsy using grasping forceps. The histopathological findings of the biopsy specimens indicated hypertrophic gastritis, and Y-U pyloroplasty was performed. However, histopathological examination of the surgically resected mass revealed tubular adenocarcinoma of the stomach. Then, carboplatin chemotherapy was performed 4 times for 13 weeks. Clinical signs, such as vomiting, were resolved gradually after surgery and chemotherapy, and the patient's condition was managed favorably until recently (30 months after surgery). This case report describes clinical features, imaging studies, endoscopic characteristics and histopathological and immunohistochemical features of gastric tubular adenocarcinoma as early gastric cancer in a dog. PMID:24646602

  1. Anti-tumour efficacy of calusterone against DMBA-induced rat mammary adenocarcinoma in vivo and in organ culture.

    PubMed Central

    Horn, H.; Erlichman, I.; Levij, I. S.

    1976-01-01

    The effect of calusterone (7beta,17alpha-dimethyltestosterone) on rat mammary DMBA-induced adenocarcinoma was studied both in vivo and in organ culture. In vivo all 8 tumours with a diameter of less than 30 mm regressed following calusterone injection (10 mg/day for 2-3 weeks). In organ culture calusterone (20 mug/ml medium) inhibited the synthesis of DNA and RNA in all 7 cases examined. Testosterone also inhibited the synthesis of DNA and RNA in organ culture in 12 out of 14 and 10 out of 14 tumours respectively. Oestradiol-17beta on the other hand had no effect on DNA and RNA synthesis in organ culture although 70% of the tumours examined were ovarian dependent, i.e. regressed following castration. This could be explained by the direct effect of calusterone on rat adenocarcinoma compared with the indirect effect of oestradiol-17beta which probably exerts its action by activating the secretion of prolactin which acts on the tumour. PMID:131571

  2. Immunohistochemical expression of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 in canine simple mammary gland adenocarcinomas

    PubMed Central

    Al-Dissi, Ahmad N.; Haines, Deborah M.; Singh, Baljit; Kidney, Beverly A.

    2010-01-01

    The expression of 5 markers associated with angiogenesis, proliferation, and apoptosis was studied in 26 canine simple mammary gland adenocarcinomas (SMGAs). The adenocarcinomas were graded histologically, and tissue sections were immunohistochemically stained for the expression of vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), intra-tumor microvessel density, and tumor proliferation (PI) using antibodies against VEGF, VEGFR-2, von Willebrand factor, and Ki-67 antigen, respectively. Apoptotic indices (AI) were determined by an apoptosis assay. Markers VEGF and VEGFR-2 were detected in 96% and 100% of SMGAs, respectively. A high correlation between histologic grade and PI (r = 0.73), a moderate correlation between VEGF and histologic grade (r = 0.33), and between VEGF and PI (r = 0.42) were found. There was a significant difference in median PI among the 3 histologic grade groups (r < 0.05). Vascular endothelial growth factor may stimulate tumor cell proliferation through an autocrine loop, since VEGF and VEGFR-2 were expressed in most tumors. PMID:21197202

  3. Consumption of silibinin, a flavonolignan from milk thistle, and mammary cancer development in the C3(1) SV40 T,t antigen transgenic multiple mammary adenocarcinoma (TAg) mouse.

    PubMed

    Verschoyle, Richard D; Brown, Karen; Steward, William P; Gescher, Andreas J

    2008-07-01

    Silibinin is a flavonolignan extracted from milk thistle with cancer chemopreventive activity in preclinical models of prostate and colorectal cancer. A milk thistle extract, of which silibin is a major component, has recently been shown to exacerbate mammary carcinogenesis in two rodent models. We tested the hypothesis that consumption of silibinin or silipide, a silibinin formulation with pharmaceutical properties superior to the unformulated agent, affect breast cancer development in the C3(1) SV40 T,t antigen transgenic multiple mammary adenocarcinoma mouse model. Mice received silibinin or silipide (0.2% silibinin equivalents) with their diet from weaning, and tumour development was monitored by weekly palpation and the number and weight of neoplasms at the end of the experiment. Intervention neither promoted, nor interfered with, tumour development. The result suggests that promotion of carcinogenesis is not a feature of silibinin consistent across rodent models of mammary carcinogenesis. PMID:17909802

  4. Oestrogen and progesterone receptor expression in subtypes of canine mammary tumours in intact and ovariectomised dogs.

    PubMed

    Mainenti, M; Rasotto, R; Carnier, P; Zappulli, V

    2014-10-01

    The objective of this study was to investigate as a potential prognostic indicator the relationship between histological subtype of canine mammary tumours (CMTs) and oestrogen-α (ORα) and progesterone (PR) receptor expression. Using immunohistochemistry, receptor expression in neoplastic epithelial cells was assessed in 12 different subtypes in 113 CMTs (34 benign, 79 malignant) and 101 surrounding normal tissues. Sixty-eight and 45 CMTs were from intact and ovariectomised bitches, respectively. Histological subtype strongly influenced ORα/PR expression: simple and complex adenomas as well as simple tubular carcinomas exhibited the greatest expression, whereas immunohistochemical labelling for these receptors was weakest in carcinoma and malignant myoepitheliomas, as well as in solid/anaplastic carcinomas and comedocarcinomas. Receptor expression was generally higher in benign relative to malignant neoplasms, and in the latter it was significantly lower in ovariectomised vs. intact bitches. Lymphatic invasion, mitotic index, nodule diameter, and tumour grade were significantly associated with ORα/PR expression. Although not found to be an independent prognostic indicator, tumours from dogs with <10% cells with ORα/PR expression had a poorer prognosis. Lymphatic invasion, the state of the margins of excision, and mitotic index were found to be independent prognostic indicators. Overall, the results suggest that differences in histological subtype and whether or not a bitch has been ovariectomised should be considered when evaluating the significance of ORα and PR expression in CMTs. PMID:24980810

  5. Oestrogen (ER) and progestin receptors (PR) in mammary tissue of the female dog: different receptor profile in non-malignant and malignant states.

    PubMed Central

    Rutteman, G. R.; Misdorp, W.; Blankenstein, M. A.; van den Brom, W. E.

    1988-01-01

    Oestrogen (ER) and progestin receptors (PR) were measured in cytosols from histologically normal mammary tissues (n = 30), and in benign (n = 59) and malignant mammary lesions (n = 49) from female dogs. Receptor levels greater than or equal to 5 fmol mg-1 protein were considered positive. The presence of histologically normal mammary epithelium within specimens of primary tumours was noticed as a factor that may cause false-positive receptor results. Receptor levels in non-malignant tissues, and the receptor status of primary cancers did not vary significantly with regard to the phase of oestrous cycle (anoestrus/metoestrus) or the influence of exogenous progestins. ER- or PR-positivity was more frequent and levels of both receptors were higher in 'normal' tissues and in benign lesions than in primary cancers (P less than 0.001). ER and PR levels were higher in benign lesions of dogs also developing malignant mammary tumours than in benign lesions of dogs that did not (P less than 0.02 and P less than 0.05, respectively). Regional and distant cancer metastases were frequently receptor-negative. In some dogs heterogeneity of receptor status was found between different sites of the same cancer. These findings indicate that in non-malignant mammary tissues of adult female dogs expression of the genes encoding ER and PR is common. In malignant tumours this property may become lost, in particular in advanced states of disease. PMID:3219269

  6. Altered expression of glycosaminoglycans in metastatic 13762NF rat mammary adenocarcinoma cells

    SciTech Connect

    Steck, P.A.; Cheong, P.H.; Nakajima, M.; Yung, W.K.A.; Moser, R.P.; Nicolson, G.L.

    1987-02-24

    A difference in the expression and metabolism of (/sup 35/S)sulfated glycosaminoglycans between rat mammary tumor cells derived from a primary tumor and those from its metastatic lesions has been observed. Cells from the primary tumor possessed about equal quantities of chondroitin sulfate and heparan sulfate on their cell surfaces but released fourfold more chondroitin sulfate than heparan sulfate into their medium. In contrast, cells from distal metastatic lesions expressed approximately 5 times more heparan sulfate than chondroitin sulfate in both medium and cell surface fractions. This was observed to be the result of differential synthesis of the glycosaminoglycans and not of major structural alterations of the individual glycosaminoglycans. The degree of sulfation and size of heparan sulfate were similar for all cells examined. However, chondroitin sulfate, observed to be only chondroitin 4-sulfate, from the metastases-derived cells had a smaller average molecular weight on gel filtration chromatography and showed a decreased quantity of sulfated disaccharides upon degradation with chondroitin ABC lyase compared to the primary tumor derived cells. Major qualitative or quantitative alterations were not observed for hyaluronic acid among the various 13762NF cells. The metabolism of newly synthesized sulfated glycosaminoglycans was also different between cells from primary tumor and metastases. A pulse-chase kinetics study demonstrated that both heparan sulfate and chondroitin sulfate were degraded by the metastases-derived cells, whereas the primary tumor derived cells degraded only heparan sulfate and degraded it at a slower rate. These results suggested that altered glycosaminoglycan expression and metabolism may be associated with the metastatic process in 13762NF rat mammary tumor cells.

  7. Marginal activity of progesterone receptor B (PR-B) in dogs but high incidence of mammary cancer.

    PubMed

    Gracanin, Ana; Voorwald, Fabiana A; van Wolferen, Monique; Timmermans-Sprang, Elpetra; Mol, Jan A

    2014-10-01

    Progesterone plays an important role in the normal development and carcinogenesis of the mammary gland. In vitro studies have shown that the canine progesterone receptor B (cPR-B), which is essential for mammary development in the mouse, does not transactivate reporter constructs containing progesterone response elements. Therefore, the question was raised whether the cPR-B was completely devoid of transactivation potential of endogenous progesterone regulated genes. Canine mammary cell lines expressing doxycycline-inducible cPR-B, human PR-B or a chimera in which the canine B-upstream segment (BUS) was replaced by a human BUS were treated for 24h with doxycycline, progesterone or a combination of the two. The expression profiling was subsequently performed using a dog-specific microarray and miRNA primers. Incubation of stably transfected cell lines with doxycycline or progesterone alone, did not change expression of any endogenous gene. Expression of activated human PR-B or the chimera of human BUS with the canine PR resulted in differential expression of >500 genes whereas the activated cPR-B regulated only a subset of 40 genes and to a limited extent. The relevance of the marginal transactivation potential or the consequence of a lack of cPR-B function for the carcinogenesis of mammary gland tumors is discussed. PMID:25158022

  8. Immunohistochemical identification method of tumour cells in the S phase of mitotic cycle and its usefulness in diagnostics of mammary gland adenocarcinomas in bitches.

    PubMed

    Nowak, M; Madej, J A; Dziegiel, P; Kanzawa, H

    2006-01-01

    The studies aimed at identification of neoplastic cells at the S phase of mitotic cycle in mammary gland adenocarcinomas of bitches. The material was sampled from bitches of various races, aging 6 to 12 years, in which the mammary gland tumours developed spontaneously. The tumours were verified histopathologically and, then, immunohistochemical reactions were performed in order to detect cells which had incorporated BrdU (bromodeoxyuridine), contained Ki-67 or PCNA antigen. The histological preparations were photographed and obtained pictures were subjected to computer-assisted image analysis using Axiophot microscope (Carl Zeiss) coupled to a computer and the Multi-ScaneBase V 8.08 software, working under Windows. Fifty percent of sections from mammary gland adenocarcinomas demonstrated BrdU labelling index of 4-5%, 40% of 1-3%, while in the remaining 10% of examined tumours no BrdU incorporation could be demonstrated. No evident relationship could be detected between the presence of BrdU incorporation and Ki-67 or PCNA antigen presence but a significant correlation was demonstrated between the expression of Ki-67 and PCNA. PMID:16573276

  9. Glycosaminoglycan synthesis by subpopulations of epithelial cells from a mammary adenocarcinoma

    SciTech Connect

    Angello, J.C.; Danielson, K.G.; Anderson, L.W.; Hosick, H.L.

    1982-06-01

    Glycosaminoglycan synthesis by two subpopulations of a mouse mammary tumor cell line was compared. The two sublines express distinctly different growth characteristics in vitro and in vivo which indicate differences in growth regulation. Newly made glycosaminoglycans were recovered from the culture media, the cell surfaces, and residual cellular material. The cell population which grows more aggressively in vivo (+SA subline, a subline that grows in soft agarose) incorporated about 8 times more (/sup 14/C)glucosamine per cell into total glycosaminoglycans than did the slower-growing population (-SA subline, which does not grow in soft agarose). Appropriate control experiments indicated that the apparent difference in rates of synthesis was not due to discrepancies in glucosamine uptake. The main residual cellular molecule labeled was heparan sulfate, but the predominant molecule at the cell surface and in the culture fluid was hyaluronic acid. Overall, +SA cells synthesized more hyaluronic acid and -SA cells synthesized more heparan sulfate; in both cell populations, these two molecules accounted for about 90% of total glycosaminoglycans produced.

  10. Ultrasonographic evaluation of depth-width ratio (D/W) of benign and malignant mammary tumors in dogs.

    PubMed

    Tagawa, Michihito; Kanai, Eiichi; Shimbo, Genya; Kano, Mikiya; Kayanuma, Hideki

    2016-04-01

    Depth-width ratio (D/W) is the only quantitative item in the criteria recommended by the Japanese Ultrasound Society for the evaluation of breast tumors in humans. However, the usefulness of the D/W has not been evaluated in dogs. Eighty-six mammary masses in 34 female dogs underwent ultrasonographic examination to determine the D/W and other characteristics. Results of ultrasonographic and histopathologic examinations were compared. The D/W of malignant tumors was significantly greater than that of benign tumors, and it had a sensitivity of 56.3% and a specificity of 92.9% for the diagnosis of malignancy when the threshold of D/W was 0.7. In addition, irregular margin, polymorphous shape and heterogeneous internal echographic characteristics were correlated with malignancy. PMID:26596466

  11. High and low dose radiation effects on mammary adenocarcinoma cells – an epigenetic connection

    PubMed Central

    Luzhna, Lidia; Filkowski, Jody; Kovalchuk, Olga

    2016-01-01

    The successful treatment of cancer, including breast cancer, depends largely on radiation therapy and proper diagnostics. The effect of ionizing radiation on cells and tissues depends on the radiation dose and energy level, but there is insufficient evidence concerning how tumor cells respond to the low and high doses of radiation that are often used in medical diagnostic and treatment modalities. The purpose of this study was to investigate radiation-induced gene expression changes in the MCF-7 breast adenocarcinoma cell line. Using microarray technology tools, we were able to screen the differential gene expressions profiles between various radiation doses applied to MCF-7 cells. Here, we report the substantial alteration in the expression level of genes after high-dose treatment. In contrast, no dramatic gene expression alterations were noticed after the application of low and medium doses of radiation. In response to a high radiation dose, MCF-7 cells exhibited down-regulation of biological pathways such as cell cycle, DNA replication, and DNA repair and activation of the p53 pathway. Similar dose-dependent responses were seen on the epigenetic level, which was tested by a microRNA expression analysis. MicroRNA analysis showed dose-dependent radiation-induced microRNA expression alterations that were associated with cell cycle arrest and cell death. An increased rate of apoptosis was determined by an Annexin V assay. The results of this study showed that high doses of radiation affect gene expression genetically and epigenetically, leading to alterations in cell cycle, DNA replication, and apoptosis. PMID:27226982

  12. Mammary gland cancer in a colony of beagle dogs: Inheritance, and p53 & erbB-2 expression

    SciTech Connect

    Kelly, G.; Griffith, W.C.; Muggenburg, Tierney, L.A.; Lechner, J.F.; Hahn, F.F.

    1994-11-01

    One American woman in nine will be diagnosed with breast cancer in her lifetime. This somber statistic translates into 182,000 new diagnoses and 46,000 deaths per year. Efforts to decrease breast cancer mortality have focused on early detection and improved treatment. Such efforts would be facilitated by the identification of individuals predisposed to the disease. A family history of the disease can increase a woman`s risk for developing breast cancer by two- to six-fold. Inheritance of this disease is consistent with at least one susceptibility locus on chromosome 17 (17q12-21) with incomplete penetrance. However, other mechanisms of inherited susceptibility also contribute to the high incidence of the disease. The purpose of the present study was to characterize familial pattern of mammary cancer development in the dog colony. In addition, the expression of the p53 tumor supressor gene and c-erbB2 (p185{sup erbB2}) oncogene proteins, which are frequently altered in human breast cancer, were examined in dogs susceptible and resistant to mammary cancer.

  13. Plasma biomarkers profile of female dogs with mammary carcinoma and its association with clinical and pathological features.

    PubMed

    Estrela-Lima, A; Araújo, M S S; Soares, R P; Ribeiro, L G R; Damasceno, K A; Costa, A T; Teixeira-Carvalho, A; Martins-Filho, O A; Cassali, G D

    2016-03-01

    The immunological biomarkers profiles were evaluated using Luminex as putative measures to monitor canine mammary carcinomas (MCs). Forty female dogs were categorized into benign mixed tumour (MC-BMT = 28) and mammary carcinoma (MC=12). The ascendant biomarker signatures were used to compare the groups. For example, a higher frequency of MC-BMT animals producing IL-6, CXCL-8 and CXCL-10 was observed, whereas for the MC group IL-2 and CXCL-8 were detected. MC-BMT animals without metastasis had an increase in the levels of IL-2, CXCL-8, CXCL-10, IL-6, TNF-α, IL-15 and a decrease in IL-10 and CXCL-8. MC-BMT animals with metastasis showed only an increase in CXCL-10 and a decrease in IL-18. After comparing the ascendant signatures following the presence of metastasis in both groups, a higher frequency of dogs exhibiting IL-10 production was observed. Pearson correlation (P = 0.0273) and receiver operating characteristic (ROC) curve analysis revealed that this pattern was associated with worse outcome and lower survival rates in MC animals. PMID:24571435

  14. The effect of neutering on the risk of mammary tumours in dogs--a systematic review.

    PubMed

    Beauvais, W; Cardwell, J M; Brodbelt, D C

    2012-06-01

    A commonly-stated advantage of neutering bitches is a significant reduction in the risk of mammary tumours, however the evidence for this has not previously been assessed by systematic review. The objectives of this study were to estimate the magnitude and strength of evidence for any effect of neutering, or age of neutering, on the risk of mammary tumours in bitches. A systematic review was conducted based on Cochrane guidelines. Peer-reviewed analytic journal articles in English were eligible and were assessed for risk of bias by two reviewers independently. Of 11,149 search results, 13 reports in English-language peer-reviewed journals addressed the association between neutering/age at neutering and mammary tumours. Nine were judged to have a high risk of bias. The remaining four were classified as having a moderate risk of bias. One study found an association between neutering and a reduced risk of mammary tumours. Two studies found no evidence of an association. One reported "some protective effect" of neutering on the risk of mammary tumours, but no numbers were presented. Due to the limited evidence available and the risk of bias in the published results, the evidence that neutering reduces the risk of mammary neoplasia, and the evidence that age at neutering has an effect, are judged to be weak and are not a sound basis for firm recommendations. PMID:22647210

  15. Evaluation of an anal sac adenocarcinoma tumor in a Spitz dog

    PubMed Central

    Javanbakht, Javad; Tavassoli, Abbas; Sabbagh, Atefeh; Hassan, Mehdy Aghamohammmad; Samakkhah, Shohreh Alian; Shafiee, Radmehr; Lakzian, Ali; Ghalee, Vahideh Rahmani; Gharebagh, Sonia Shoja

    2013-01-01

    A 9-year-old emasculated male Spitz with tenesmus and constipation had a subcutaneous mass at the left ventral aspect of the anus with history of polyuria and polydipsia. A complete blood cell count, serum biochemistry panel, and urinalysis (cystocentesis sample) were evaluated. Abnormalities in the serum biochemistry panel included a mildly elevated serum cholesterol concentration (7.28 mmol/L; reference interval, 2.70–5.94 mmol/L), increased serum alkaline phosphatase activity (184 U/L; reference interval, 9–90 U/L), alanine transaminase (122 U/L; reference interval, 5–60 U/L) activity and aspartate aminotransferase (80 U/L; reference interval, 5–55 U/L) activity, severe increased total calcium concentration (16.3 mg/dL; reference interval, 8.2–12.4 mg/dL or 9.3–11.4 mg/dL), and decreased total calcium concentration (3.4 mg/dL, reference interval, 2.5–5.6mg/dL). Furthermore, testing revealed an increased intact parathyroid hormone concentration (38.6 pmol/L; reference interval, 3–17 pmol/L). On cytologic and histopathologic examinations, various types of cells were observed. Most of the cells were oval to polygonal and had elliptical or elongate nuclei and a moderate amount of pale to basophilic cytoplasm. The remaining cells had round to oval nuclei and pale to basophilic cytoplasm. Cells of both types were loosely adhered to each other and were arranged in rosette-like structures. Both neoplastic cell types had fine homogenous chromatin and either a small indistinct nucleolus or no visible nucleolus. Mild anisokaryosis and anisocytosis were observed. Histologically, the mass consists of glandular structures formed by cuboidal cells admixed with bundles of spindle cells. Based on location and histologic features, the final diagnosis was adenocarcinoma of the apocrine gland of the anal sac, which should be included as a cytologic differential diagnosis when spindle cells and typical epithelial cells are observed in masses in the region of the anal

  16. Comparison of estrogen and progesterone receptor expression in normal and tumor mammary tissues from dogs.

    PubMed

    Donnay, I; Rauïs, J; Devleeschouwer, N; Wouters-Ballman, P; Leclercq, G; Verstegen, J

    1995-09-01

    Concentrations of estrogen (ER) and progesterone (PR) receptors were measured by radioreceptor assay in tumor (n = 319) and normal (n = 166) mammary tissue from 248 bitches. Correlations between ER and PR and between receptor expression in tumor and normal mammary tissue from the same bitches were evaluated. The influence of tumor, clinical, or hormonal variables on receptor expression also was studied. Approximately 80% of tumor and 95% of normal mammary tissue expressed detectable concentrations of ER, PR, or both. Direct correlation was found between ER and PR concentrations in normal and tumor tissues. Median ER concentrations were significantly higher (46 +/- 47 fmol/mg of cytosolic protein vs 27 +/- 24 fmol/mg of cytosolic protein; P = 0.0002) in normal than in tumor tissue. On the other hand, PR concentrations were significantly higher (57 +/- 52 fmol/mg vs 77 +/- 99 fmol/mg; P = 0.03) in tumors (especially benign tumors) than in normal tissue. Poorly differentiated malignant tumors expressed lower concentrations of receptors than did benign or well differentiated malignant tumors. The ER and PR concentrations decreased with increasing size of the lesion. Hormonal status of the bitch significantly (P < 0.05) influenced receptor expression in normal tissue: bitches in the luteal phase of the estrous cycle had higher concentrations of ER (69 +/- 62 fmol/mg) than did ovariectomized bitches (24 +/- 19 fmol/mg) or bitches in anestrus (38 +/- 45 fmol/mg) or the follicular phase (13 +/- 7 fmol/mg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7486397

  17. [Analysis of mammary gland tumors in dogs in the South Bohemian Region].

    PubMed

    Mátl, J

    1990-09-01

    149 biopsies and excisions of tumorous tissues of the mammary gland it bitches were examined histologically at a workplace of the State Veterinary Institute at Ceské Budĕjovice in the years 1970 to 1987. The tumours were classified according to the criteria recommended by the WHO classification system. The tumours were divided into three groups with respect to their histogenesis: epithelial (58.4%), mesenchymatous (2%) and mixed (39.6%). The ratio of malignant to benign tumours made 65.1% to 34.9%. PMID:2100434

  18. CT and PET-CT of a Dog with Multiple Pulmonary Adenocarcinoma

    PubMed Central

    KIM, Jisun; KWON, Seong Young; CENA, Rohani; PARK, Seungjo; OH, Juyeon; OUI, Heejin; CHO, Kyoung-Oh; MIN, Jung-Joon; CHOI, Jihye

    2013-01-01

    ABSTRACT A 10-year-old, intact female Yorkshire terrier had multiple pulmonary nodules on thoracic radiography and ultrasonography with no lesions elsewhere. Computed tomography (CT) and positron emission tomography and computed tomography (PET-CT) using 18F-fluorodeoxyglucose (FDG) were performed to identify metastasis and undetected primary tumors. On CT examination, pulmonary nodules had a hypoattenuating center with thin peripheral enhancement, suggesting ischemic or necrotizing lesion. In PET-CT at 47 min after intravenous injection of 11.1 MBq/kg of FDG, the maximum standardized uptake value of each pulmonary nodule was about from 3.8 to 6.4. There were no abnormal lesions except for four pulmonary nodules on the CT and PET-CT. Primary lung tumor was tentatively diagnosed, and palliative therapy using 2 mg/kg tramadol and 2.2 mg/kg carprofen twice per day was applied. After the dog’s euthanasia due to deteriorated clinical signs and poor prognosis, undifferentiated pulmonary adenocarcinoma was diagnosed through histopathologic and immunochemistry examination. To the best of the authors’ knowledge, this is the first study of CT and PET-CT features of canine pulmonary adenocarcinoma. In this case, multiple pulmonary adenocarcinoma could be determined on the basis of FDG PET-CT through screening the obvious distant metastasis and/or lymph node invasions and excluding unknown primary tumors. PMID:24389742

  19. Expression of E-cadherin, beta-catenin and Ki-67 antigen and their reciprocal relationships in mammary adenocarcinomas in bitches.

    PubMed

    Nowak, Marcin; Madej, Janusz A; Dziegiel, Piotr

    2007-01-01

    In progression of tumours, resulting from, i.e., release of cells from the parental tumour and development of metastases, expression of cell adhesion molecules (CAM) plays a significant role. CAM, including E-cadherin and the linked to it beta-catenin, determine the extent of adhesion between normal and neoplastically altered cells. Moreover, the unbound form of beta-catenin in a cell nucleus may affect the rate of cell proliferation This study aimed at demonstrating intensity and localisation of E-cadherin and beta-catenin expression as related to expression of the proliferation-associated antigen, Ki-67 in mammary adenocarcinomas of bitches. The study was performed on 35 cases of the above mentioned tumours. On paraffin sections immunohistochemical reactions were performed using monoclonal antibodies directed against E-cadherin, beta-catenin and Ki-67 antigen. In the studies a membranous expression of E-cadherin, a cytoplasmic-nuclear expression of beta-catenin and nuclear expression of Ki-67 antigen were demonstrated. Statistical calculations using Spearman's test demonstrated a pronounced positive correlation between expression of beta-catenin and Ki-67 antigen and absence of correlation between expression of E-cadherin and Ki-67 antigen. No correlation could be detected between expression intensities of E-cadherin and beta-catenin. PMID:17951173

  20. Inhibitory effects of a polypeptide thymic factor on the development of 7,12-dimethylbenz(a)anthragene-induced mammary adenocarcinoma in female rats

    SciTech Connect

    Anisimov, V.N.; Danetskaya, E.V.; Morozov, V.G.; Khavinson, V.Kh.

    1980-01-01

    It has come to be recognized that tumor growth is accompanied by inhibition of cellular immunity and the function of the T lymphocytes. Restitution of T lymphocyte function by means of several pharmacologic agents such as levamisole, phenformin, or epithalamin (an epiphyseal factor) has, in a number of cases, been accompanied by growth inhibition of both spontaneous and induced tumors. In addition, the importance of the thymus in the regulation of T lymphocytes and in antitumor immunity has been recognized. Several indicators point to the fact that the thymus contains physiologically active substances which stimulate T cell-dependent immunity and prevent the occurrence of neoplasms. These considerations have led to attempts at isolation of active thymic factors and studies on their effects on the appearance and growth of tumors. Previously, a thymic factor - thymarin - had been isolated which imparted immunocompetence to the T lymphocytes. This factor differs from other thymic preparations, including thymosine, in terms of a number of physicochemical characteristics and is a polypeptide with a molecular weight of 5000. This study is concerned with its effects on tumor development - mammary gland adenocarcinoma induced in animals with a chemical carcinogen.

  1. [Mammary carcinoma of the female dog: clinical relevance of the immunohistochemical demonstration of micrometastases in the regional lymph nodes].

    PubMed

    Busch, U; Rudolph, R

    1995-06-01

    77 formalin-fixed and paraffin-embedded mammary carcinomas and the regional lymph nodes of bitches were examined by immunocytochemical technique, all of them free of metastases in routine HE-staining. To compare the two methods, two serial sections were cut of three parts of the lymph nodes. One was used for incubation with the antibody AE1, which reacts with cytokeratin subtype I/A, the other for staining with HE. From 60 of the 77 bitches we received information about the operation and the follow up study period (surgical method, new tumours, survival rate and causes of death). These data were compared with the immunocytochemical results of the lymph nodes. In 84.4% of all 77 lymph nodes tumour cell embolism and/or micrometastases were detected. Comparing the two methods, we found that with HE-staining it was only possible to detect two thirds of all micrometastases containing more than 50 tumor cells. Smaller micrometastases were suspicious in a few cases, the majority could not be detected at all. In the follow up study there was evidence of a better prognosis for bitches with tumours detected in an early stage of growth and treated with radical mastectomy. This was independent of a positive or negative result of tumour cells in lymph nodes. The presence of cancer cells in lymph nodes was only important, if either the tumour was treated in an advanced stage or only single complexes or tumour nodes were extirpated. These dogs often showed metastases in the lung. PMID:7545833

  2. Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6-NTRK3 fusion.

    PubMed

    Dogan, Snjezana; Wang, Lu; Ptashkin, Ryan N; Dawson, Robert R; Shah, Jatin P; Sherman, Eric J; Michael Tuttle, R; Fagin, James A; Klimstra, David S; Katabi, Nora; Ghossein, Ronald A

    2016-09-01

    ETV6-NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype. Fluorescence in situ hybridization for ETV6 rearrangement was performed in three, and the next-generation sequencing assay MSK-IMPACT™ (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) was performed in two cases. Primary MASC of the thyroid occurred in two women and one man, age 47-72 years. All patients presented with high T stage, infiltrative, locally aggressive tumors with extrathyroidal extension. Two cases were associated with well-differentiated papillary thyroid carcinoma. Histologically, they appeared as low-grade tumors, resembling MASC of the salivary glands and labeled positive for mammaglobin, GCDFP-15, S-100 protein, p63, weakly positive for PAX8, and negative for TTF-1 and thyroglobulin. Fluorescence in situ hybridization revealed ETV6 rearrangement in all cases. In two tested cases MSK-IMPACT™ confirmed the presence of ETV6-NTRK3 gene fusion. Two patients had at least two local recurrences, one was alive with disease, and one was alive and free of disease after 14 and 17 years, respectively. The third patient was alive and free of disease after 2 years. MASC of the thyroid is histologically, immunophenotypically, and genetically similar to its salivary gland counterpart. Thyroid MASC can be associated with a well-differentiated papillary thyroid carcinoma component, supporting follicular cell origin. Clinically, these carcinomas may show frequent recurrences but are associated with long

  3. Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6–NTRK3 fusion

    PubMed Central

    Dogan, Snjezana; Wang, Lu; Ptashkin, Ryan N; Dawson, Robert R; Shah, Jatin P; Sherman, Eric J; Tuttle, R Michael; Fagin, James A; Klimstra, David S; Katabi, Nora; Ghossein, Ronald A

    2016-01-01

    ETV6–NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype. Fluorescence in situ hybridization for ETV6 rearrangement was performed in three, and the next-generation sequencing assay MSK-IMPACT™ (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) was performed in two cases. Primary MASC of the thyroid occurred in two women and one man, age 47–72 years. All patients presented with high T stage, infiltrative, locally aggressive tumors with extrathyroidal extension. Two cases were associated with well-differentiated papillary thyroid carcinoma. Histologically, they appeared as low-grade tumors, resembling MASC of the salivary glands and labeled positive for mammaglobin, GCDFP-15, S-100 protein, p63, weakly positive for PAX8, and negative for TTF-1 and thyroglobulin. Fluorescence in situ hybridization revealed ETV6 rearrangement in all cases. In two tested cases MSK-IMPACT™ confirmed the presence of ETV6–NTRK3 gene fusion. Two patients had at least two local recurrences, one was alive with disease, and one was alive and free of disease after 14 and 17 years, respectively. The third patient was alive and free of disease after 2 years. MASC of the thyroid is histologically, immunophenotypically, and genetically similar to its salivary gland counterpart. Thyroid MASC can be associated with a well-differentiated papillary thyroid carcinoma component, supporting follicular cell origin. Clinically, these carcinomas may show frequent recurrences but are associated

  4. Transforming growth factor-beta activities in 'in vivo' lines of hormone-dependent and independent mammary adenocarcinomas induced by medroxyprogesterone acetate in BALB/c mice.

    PubMed

    Elizalde, P V; Lanari, C; Kordon, E; Tezón, J; Charreau, E H

    1990-07-01

    We have determined the presence of transforming growth factor-beta (TGF-beta)-like polypeptides in mammary adenocarcinomas induced by medroxyprogesterone acetate (MPA) in BALB/c mice. In hormone-dependent tumors (HD) from nontreated and MPA-treated mice a high molecular weight (43 kDa) transforming activity was purified by Bio-Gel P-60 chromatography. This TGF was able to confer the neoplastic phenotype on NRK-49F cells without the addition of epidermal growth factor (EGF), though its activity was potentiated by EGF. It did not compete for binding to the EGF receptor, had no mitogenic activity on monolayer cultures of NRK fibroblasts, and was a potent inhibitor of DNA synthesis induced in these cells by EGF and insulin. In HD and hormone-independent tumors (HI) another TGF with a Mr of 13 kDa was isolated. This transforming activity showed the same biological properties as 43 kDa TGF, with the exception that in the absence of EGF it did not stimulate soft agar growth of NRK-49F cells. The synthesis of both factors in 'in vivo' HD tumors seems to be under MPA control, since it is much lower in HD tumors from MPA-treated mice. Further purification of the 13 and 43 kDa TGFs by hydrophobic interaction HPLC demonstrated that each one eluted in a different position, and that their elution profile differed from the TGF-beta from human platelets. The biological activity of the 13 and 43 kDa TGFs was not neutralized by a specific anti-TGF-beta antibody. PMID:2145045

  5. Dogs

    MedlinePlus

    ... found on the skin of people and animals. Methicillin-resistant Staphylococcus aureus (MRSA) is the same bacterium that has become resistant to some antibiotics. Dogs and other animals often can carry MRSA ...

  6. Cutaneous metastases of a mammary carcinoma in a llama.

    PubMed Central

    Leichner, T L; Turner, O; Mason, G L; Barrington, G M

    2001-01-01

    An 8-year-old, female llama was evaluated for nonhealing, ulcerative, cutaneous lesions, which also involved the mammary gland. Biopsies of the lesions distant from and within the mammary gland area revealed an aggressive carcinoma. The tumor was confirmed at necropsy to be a mammary gland adenocarcinoma with cutaneous metastasis. Images Figure 1. PMID:11265189

  7. CLINICOPATHOLOGIC FEATURES OF MAMMARY MASSES IN CAPTIVE LIONS (PANTHERA LEO).

    PubMed

    Sadler, Ryan A; Craig, Linden E; Ramsay, Edward C; Helmick, Kelly; Collins, Darin; Garner, Michael M

    2016-03-01

    A multi-institutional retrospective analysis of 330 pathology accessions from 285 different lions found 15 captive, female African lions (Panthera leo) with confirmed mammary masses. Aside from the presence of a mammary mass, the most common initial clinical sign was inappetence. Histologic diagnoses were predominantly adenocarcinoma (n = 12), though two benign masses (mammary hyperplasia and a mammary cyst) and one squamous cell carcinoma were identified. Nine of 13 malignant tumors had metastasized to lymph nodes or viscera at the time of necropsy. Six lions with adenocarcinoma and two lions with benign mammary masses had received hormonal contraception, though little evidence of mammary lobular hyperplasia was seen in association with the adenocarcinomas. The most common concurrent disease processes found at necropsy were chronic urinary tract disease and other malignancies. These cases demonstrate that mammary malignancies occur in captive lions and frequently metastasize. PMID:27010273

  8. Immunophenotypic features of tumor infiltrating lymphocytes from mammary carcinomas in female dogs associated with prognostic factors and survival rates

    PubMed Central

    2010-01-01

    Background The immune system plays an important role in the multifactorial biologic system during the development of neoplasias. However, the involvement of the inflammatory response in the promotion/control of malignant cells is still controversial, and the cell subsets and the mechanisms involved are poorly investigated. The goal of this study was to characterize the clinical-pathological status and the immunophenotyping profile of tumor infiltrating lymphocytes and their association with the animal survival rates in canine mammary carcinomas. Methods Fifty-one animals with mammary carcinomas, classified as carcinomas in mixed tumors-MC-BMT = 31 and carcinomas-MC = 20 were submitted to systematic clinical-pathological analysis (tumor size; presence of lymph node and pulmonary metastasis; clinical stage; histological grade; inflammatory distribution and intensity as well as the lymphocytic infiltrate intensity) and survival rates. Twenty-four animals (MC-BMT = 16 and MC = 8) were elected to the immunophenotypic study performed by flow cytometry. Results Data analysis demonstrated that clinical stage II-IV and histological grade was I more frequent in MC-BMT as compared to MC. Univariate analysis demonstrated that the intensity of inflammation (moderate/intense) and the proportion of CD4+ (≥ 66.7%) or CD8+ T-cells (<33.3%) were not associated with worse survival rate. Multivariate analysis demonstrated that only lymphocytic infiltrate intensity ≥ 600 (P = 0.02) remained as independent prognostic factor. Despite the clinical manifestation, the lymphocytes represented the predominant cell type in the tumor infiltrate. The percentage of T-cells was higher in animals with MC-BMT without metastasis, while the percentage of B-lymphocytes was greater in animals with metastasized MC-BMT (P < 0.05). The relative percentage of CD4+ T-cells was significantly greater in metastasized tumors (both MC-BMT and MC), (P < 0.05) while the proportion of CD8+ T-cells was higher in

  9. Mammary and extramammary Paget's disease

    PubMed Central

    Lloyd, J; Flanagan, A

    2000-01-01

    Mammary and extramammary Paget's disease are uncommon intraepithelial adenocarcinomas. Both conditions have similar clinical features, which mimic inflammatory and infective diseases. Histological diagnostic confusion can arise between Paget's disease and other neoplastic conditions affecting the skin, with the most common differential diagnoses being malignant melanoma and atypical squamous disease. The glandular differentiation of both mammary Paget's disease and extramammary Paget's disease is indicated by morphological appearances, the presence of intracellular mucin in many cases, and positive immunohistochemical staining for glandular cytokeratins, epithelial membrane antigen, and carcinoembryonic antigen. This article provides an overview of mammary and extramammary Paget's disease and discusses recent evidence regarding the cell of origin. The concepts of primary and secondary Paget's disease are presented and the differential diagnosis is discussed with reference to immunohistochemical markers that might be of diagnostic value. Key Words: mammary Paget's disease • extramammary Paget's disease PMID:11064666

  10. Diagnosis, classification and grading of canine mammary tumours as a model to study human breast cancer: an Clinico-Cytohistopathological study with environmental factors influencing public health and medicine

    PubMed Central

    2013-01-01

    Background The human “Elston and Ellis grading method” was utilized in dogs with mammary tumor to examine its relation to prognosis in this species, based on a 2-year follow-up period. Although cytopathology is widely used for early diagnosis of human neoplasms, it is not commonly performed in veterinary medicine. Our objectives in this study were to identify cytopathology criteria of malignancy for canine mammary tumors and the frequency of different types of mammary lesions and their relationship with histologic grade was investigated. Another aim of this study was to differentiate the simple and adenocarcinoma tumors from the complex or mixed tumor described by Elston and Ellis grading method. Methods The study was performed in 15 pure or mixed-breed female dogs submitted to surgical resections of mammary tumours. The mammary tumours were excised by simple mastectomy or regional mastectomy, with or without the superficial inguinal lymph nodes. Female dogs were mainly terriers (9 dogs) or mixed (3 dogs), the 3 other animals were a German shepherd, Dachshund and Pekingese. Before surgical excision of the tumour, FNAC was performed using a 0.6 mm diameter needle attached to a 10 ml syringe held in a standard metal syringe holder. The cytological sample was smeared onto a glass slide and either air-dried for May-Grünwald-stain, or ethanol-fixed for Papanicolaou stain and masses were surgically removed, the tumours were grossly examined and tissue samples were fixed in 10%-buffered-formalin and embedded in paraffin. Sections 4 μm thick were obtained from each sample and H&E stained. Results We obtained a correct cytohistological correlation in 14/15 cases (93.3%) when all cytopathological examinations were considered. Of the 15 cases examined, 2(13.3%) had well-differentiated (grade I), 6(40%) had moderately differentiated (grade II) and 7(46.7%) had poorly differentiated (grade III) tumours. Classification of all canine mammary gland lesions revealed 13

  11. Migrastatin Analogues Inhibit Canine Mammary Cancer Cell Migration and Invasion

    PubMed Central

    Majchrzak, Kinga; Lo Re, Daniele; Gajewska, Małgorzata; Bulkowska, Małgorzata; Homa, Agata; Pawłowski, Karol; Motyl, Tomasz; Murphy, Paul V.; Król, Magdalena

    2013-01-01

    Background Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6) on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. Results Our results showed that two of six fully synthetic analogues of migrastatin: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6) disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. Conclusion Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6) were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs. However, further in

  12. Mammary carcinogenesis in rats: basic facts and recent results in Brookhaven

    SciTech Connect

    Shellabarger, C.J.; Stone, J.P.; Holtzman, s.

    1982-01-01

    Some research results from experiments investigating neutron-induced mammary carcinogenesis in rats are presented. The additive effects of neutrons and 3-methylcholanthrene on mammary adenocarcinoma were determined. Synergism between diethylstilbestrol and neutrons was likewise studied. Differences in mammary neoplastic response between strains of laboratory rats was also investigated. (ACR)

  13. Canine mammary tumours: protective effect of late ovariectomy and stimulating effect of progestins.

    PubMed

    Misdorp, W

    1988-01-01

    Ovariectomy, even when performed at an advanced age, was found to be to some extent protective against mammary tumour development in dogs. Bitches treated with progestins had a slightly higher risk for mammary tumours (all types, benign and malignant) than controls. Progestin treatment did not increase the risk of mammary cancer. Benign tumours in (treated and untreated) dogs appeared earlier than malignant ones. Progestin treatment resulted in earlier appearance of both benign and malignant tumours than in controls. The ratio solitary/multiple mammary tumours was not significantly different between treated and untreated dogs. PMID:3376408

  14. Canine mammary tumours, an overview.

    PubMed

    Sleeckx, N; de Rooster, H; Veldhuis Kroeze, E J B; Van Ginneken, C; Van Brantegem, L

    2011-12-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Although the prevalence of these tumours decreases in regions where preventive ovari(ohyster)ectomy is performed, it remains an important disease entity in veterinary medicine. Moreover, treatment options are limited in comparison with human breast cancer. Nevertheless, recent human treatment protocols might have potential in bitches suffering from CMTs. PMID:21645126

  15. Presumptive caudal cerebellar artery infarct in a dog: clinical and MRI findings.

    PubMed

    Negrin, A; Gaitero, L; Añor, S

    2009-11-01

    Clinical signs and magnetic resonance imaging findings of a caudal cerebellar artery infarct are reported for the first time in a dog. Clinical signs were characterised by a peracute, non-progressive, right-sided central vestibular syndrome with paradoxical right-sided head tilt. Magnetic resonance images were consistent with a territorial, non-haemorrhagic, ischaemic lesion affecting the caudo-ventral part of the right cerebellar hemisphere, mainly involving the right paramedian lobe, the ansiform lobe and the caudal cerebellar peduncle. Bloodwork results were suggestive of an underlying hypercoagulable state, although the concomitant presence of a histologically confirmed mammary gland adenocarcinoma could have also been related to the cerebellar vascular obstruction through metastatic emboli formation. Posterior-inferior cerebellar artery infarction is the human equivalent of caudal cerebellar artery infarct in dogs. PMID:19891725

  16. Clinical Outcomes of Surgically Managed Spontaneous Tumors in 114 Client-owned Dogs

    PubMed Central

    Choi, Ji-Won; Yoon, Hun-Young

    2016-01-01

    Medical records of 139 tumors from 114 dogs that underwent surgery from May 2010 through March 2015 were retrospectively reviewed. Among 114 dogs, females (64.9%) were significantly more common than males (35.1%) (p<0.05). Dogs aged 6 to 10 years were more presented than non-tumor patients, however, there was no significant difference. The mean age (±SD) was 10.3±3.0 years. Although we found no significant difference of breed predisposition, the most common breed was Maltese (19.3%), followed by Shih-Tzu (14.0%), and Yorkshire terrier (13.2%). Proportional morbidity ratios (PMRs) of mammary gland, oral cavity, and skin tumors were high in Poodles, Yorkshire terriers, and Golden retrievers, respectively. Mammary gland (36.0%) was the most common site, followed by skin and soft tissues (12.2%), oral cavity (10.8%), and digestive organs (8.6%), but there was no significant difference. The objectives of surgery were curative surgery (86.2%), biopsy (4.9%), and palliative surgery (6.5%). In this study, 123 of 139 tumors had histopathological diagnoses. Adenocarcinoma was the most common type (n=24), followed by adenoma (n=17), soft tissue sarcoma (n=13), benign mixed tumor (n=5), and others (n=64). Recurrence or suspected metastasis was identified in 26 dogs. Median survival times of malignant mammary gland tumors, skin and subcutaneous tumors, and splenic tumors were 1,563.0±1,201.7, 469, and 128 days, respectively. PMID:27162528

  17. Absence of canine papillomavirus sequences in canine mammary tumours.

    PubMed

    Sardon, D; Blundell, R; Burrai, G P; Alberti, A; Tore, G; Passino, E Sanna; Antuofermo, E

    2015-01-01

    Human papillomaviruses (PVs) are found in human breast cancer tissue; however, it remains controversial as to whether these viruses play a role in the aetiology of this tumour. There has been minimal study of whether PVs are found in normal or abnormal mammary glands of animals. The present study investigated whether a PV sequence could be found in the mammary glands of 33 female dogs by rolling circle amplification and polymerase chain reaction. No PV DNA was found in normal or neoplastic canine mammary tissues, suggesting that canine PVs are probably not involved in the pathogenesis of canine mammary neoplasia. PMID:25435511

  18. Tumours and dysplasias of the mammary gland

    PubMed Central

    Hampe, J. F.; Misdorp, W.

    1974-01-01

    As mammary tumours occur frequently in the dog and cat but rarely in other domestic animals, only the tumours of these two species are classified. The epithelial tumours are termed “complex” when they consist of cells resembling both secretory and myoepithelial cells: these tumours are biologically less malignant than tumours of the “simple” type in which only one of these kinds of cell is present. The carcinomas are subdivided into adenocarcinoma, solid carcinoma, spindle cell carcinoma, anaplastic carcinoma, squamous cell carcinoma, and mucinous carcinoma. The term “carcinosarcoma or malignant mixed tumour” was used only when there were cells morphologically resembling not only one or both of the epithelial components but also connective tissue cells with their products of differentiation. The benign tumours are classed as adenoma, papilloma, fibroadenoma, or benign soft tissue tumour. The dysplasias are described under the following headings: cyst, adenosis, regular typical epithelial proliferation in ducts and lobules (epitheliosis), duct ectasia, fibrosclerosis, and lobular hyperplasia. ImagesFig. 41Fig. 42Fig. 43Fig. 44Fig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 15Fig. 16Fig. 45Fig. 46Fig. 47Fig. 48Fig. 17Fig. 18Fig. 19Fig. 20Fig. 25Fig. 26Fig. 27Fig. 28Fig. 29Fig. 30Fig. 31Fig. 32Fig. 21Fig. 22Fig. 23Fig. 24Fig. 37Fig. 38Fig. 39Fig. 40Fig. 9Fig. 10Fig. 11Fig. 12Fig. 1Fig. 2Fig. 3Fig. 4Fig. 33Fig. 34Fig. 35Fig. 36 PMID:4371737

  19. Plasma free amino acid profiles of canine mammary gland tumors

    PubMed Central

    Azuma, Kazuo; Tsuka, Takeshi; Imagawa, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

    2012-01-01

    The purpose of this study was to elucidate the relationship between plasma free amino acid (PFAA) levels and the clinical stages of mammary gland tumors (MGT) in dogs. PFAA levels in canines with malignant mammary tumors were decreased compared to those of healthy animals. The levels of aspartate and ornithine, in the dogs with tumor metastasis were significantly decreased when compared to those of dogs that did not have metastases. Results of this study indicate that PFAA levels could be a risk factor or biomarker for canine MGT metastasis. PMID:23271187

  20. Myoepithelial cells in canine mammary tumours.

    PubMed

    Sánchez-Céspedes, Raquel; Millán, Yolanda; Guil-Luna, Silvia; Reymundo, Carlos; Espinosa de Los Monteros, Antonio; Martín de Las Mulas, Juana

    2016-01-01

    Mammary tumours are the most common neoplasms of female dogs. Compared to mammary tumours of humans and cats, myoepithelial (ME) cell involvement is common in canine mammary tumours (CMT) of any subtype. Since ME cell involvement in CMT influences both histogenetic tumour classification and prognosis, correct identification of ME cells is important. This review describes immunohistochemical methods for identification of canine mammary ME cells used in vivo. In addition, phenotypic and genotypic methods to isolate ME cells for in vitro studies to analyse tumour-suppressor protein production and gene expression are discussed. The contribution of ME cells to both histogenetic classifications and the prognosis of CMT is compared with other species and the potential use of ME cells as a method to identify carcinoma in situ is discussed. PMID:26639832

  1. Cytologic analysis of the mammary papillar discharge in a canine micropapillary carcinoma.

    PubMed

    Cassali, Geovanni Dantas; Monteiro, Lidianne Narducci; Gamba, Conrado de Oliveira; Damasceno, Karine Araújo; de Campos, Cecília Bonolo; Salgado, Breno Souza

    2015-09-01

    This is a report on the cytologic analysis of the mammary papillar discharge in a 7-year-old female Doberman dog with an invasive micropapillary carcinoma. Cytologic evaluation of nipple discharge is a well-known method for the rapid diagnosis of breast cancer in women. However, there is no previous report regarding the use of this technique for assessing mammary tumors in dogs. The aim of this study was to describe the use of mammary papillar discharge cytology for diagnosing a micropapillary carcinoma in a dog. Cytologically, evaluation of the papillar discharge revealed cells arranged in clusters in a papillary pattern or in a morula-like arrangement, suggesting the diagnosis of a micropapillary carcinoma, which was subsequently confirmed by histopathology. Thus, mammary papillar discharge cytology should be considered as an ancillary method for evaluating mammary diseases in dogs. PMID:26171951

  2. [Urachal adenocarcinoma].

    PubMed

    Dakir, M; Dahami, Z; Sarf, I; Tahri, A; Elmrini, M; Benjelloun, S

    2001-09-01

    Cancer of the urachus is very unusual. The lesion is a mucosecretory adenocarcinoma. The diagnosis is usually established late, and has a serious prognosis because of a long clinical latency. We report a case of metastatic adenocarcinoma of the urachus revealed by hematuria. A review of the literature allows us to demonstrate the rarity of this tumour and to demonstrate its various clinical, histological, radiological and therapeutical aspects. PMID:11761694

  3. A Comparative Study on the In Vitro Effects of the DNA Methyltransferase Inhibitor 5-Azacytidine (5-AzaC) in Breast/Mammary Cancer of Different Mammalian Species.

    PubMed

    Harman, Rebecca M; Curtis, Theresa M; Argyle, David J; Coonrod, Scott A; Van de Walle, Gerlinde R

    2016-06-01

    Murine models are indispensible for the study of human breast cancer, but they have limitations: tumors arising spontaneously in humans must be induced in mice, and long-term follow up is limited by the short life span of rodents. In contrast, dogs and cats develop mammary tumors spontaneously and are relatively long-lived. This study examines the effects of the DNA methyltransferase (DNMT) inhibitor 5-Azacytidine (5-AzaC) on normal and tumoral mammary cell lines derived from dogs, cats and humans, as proof of concept that small companion animals are useful models of human breast cancer. Our findings show that treatment with 5-AzaC reduces in vitro tumorigenicity in all three species based on growth and invasion assays, mitochondrial activity and susceptibility to apoptosis. Interestingly, we found that the effects of 5-AzaC on gene expression varied not only between the different species but also between different tumoral cell lines within the same species, and confirmed the correlation between loss of methylation in a specific gene promotor region and increased expression of the associated gene using bisulfite sequencing. In addition, treatment with a high dose of 5-AzaC was toxic to tumoral, but not healthy, mammary cell lines from all species, indicating this drug has therapeutic potential. Importantly, we confirmed these results in primary malignant cells isolated from canine and feline adenocarcinomas. The similarities observed between the three species suggest dogs and cats can be useful models for the study of human breast cancer and the pre-clinical evaluation of novel therapeutics. PMID:27002722

  4. Canine Mammary Mixed Tumours: A Review

    PubMed Central

    Dantas Cassali, Geovanni; Cavalheiro Bertagnolli, Angélica; Ferreira, Enio; Araújo Damasceno, Karine; de Oliveira Gamba, Conrado; Bonolo de Campos, Cecília

    2012-01-01

    Mammary mixed tumours are the most frequent neoplasias in female dogs. In humans, mixed tumours are frequently found in the salivary glands and are known as pleomorphic adenomas. In addition to their histomorphologic similarities, mixed tumours and pleomorphic adenomas have the potential to become malignant and give rise to carcinomas in mixed tumours and carcinomas ex-pleomorphic adenoma, respectively. The factors associated with malignant transformation are still poorly known in the case of canine mixed tumours. However, this form of neoplasia tends to be associated with a better prognosis than other malignant histological types. This paper discusses the main features associated with female canine mammary mixed tumours. PMID:23193497

  5. Adenocarcinoma

    Cancer.gov

    Compared to adenomas, adenocarcinomas show greater cytological atypia, increased frequency of mitoses, regional variation in growth pattern, more papillary structures, have size over 5 mm in diameter, show invasion of vessels, large airways or pleura, as well as lymphatic and hematogenous metastases.

  6. Expression of the gene encoding growth hormone in the human mammary gland

    SciTech Connect

    Mol, J.A.; Misdorp, W.; Rijnberk, A.

    1995-10-01

    Progestins cause a syndrome of growth hormone (GH) excess and enhanced mammary tumorigenesis in the dog. This has been regarded as being specific for the dog. Recently we reported that progestin-induced GH excess originates from foci of hyperplastic ductular epithelium of the mammary gland in the dog. In the present report we demonstrate by reverse-transcriptase PCR and immunohistochemistry that a main factor involved in tissue growth, i.e. GH, is also expressed in normal and neoplastic human mammary glands. The gene expressed in the human mammary gland proved to be identical to the gene encoding GH in the pituitary gland. The role of progesterone in the GH expression of the human mammary gland needs, however, to be proven. It is hypothesized that this locally produced hGH may play a pathogenetic role in breast cancer. 21 refs., 2 figs., 1 tab.

  7. Progestogens and mammary tumours in the beagle bitch.

    PubMed

    Briggs, M H

    1980-03-01

    Progesterone administration induces specific cytosol receptors for progesterone in the mammary glands and uterus of adult beagle bitches but not in the mammary tissues or uterus of adult female rats. The specifiity of the progesterone receptor of dog myometrium is unlike that of human myometrium and is significantly different from progesterone receptors in tissues of th guinea pig. A spontaneous mammary benign mixed adenoma from an old beagle bitch was shown to contain specific progesterone receptors of similar affinity for progestogens as the dog uterine receptor. It is proposed that chronic toxicity tests of progestogens in the bitch cannot predict potential adverse human side effects because the regulatory mechanism for progesterone receptors is so different in the dog and major species differences exist in cytosol receptor affinity for particular progestational compounds. PMID:7414066

  8. Studies on canine mammary tumours. I. Age, seasonal and breed distribution.

    PubMed

    Boldizsár, H; Szenci, O; Muray, T; Csenki, J

    1992-01-01

    The incidence as well as age, seasonal and breed distribution of canine mammary tumours (n = 521) were studied at the Clinic of Obstetrics and Gynaecology of the University of Veterinary Science, Budapest, between 1985 and 1989. In 39 cases of mammary tumour, blood plasma oestradiol (E2) and progesterone (P) concentrations were also determined. Of all dogs referred to the clinics of the University in 1985, 0.7% had mammary tumour. On the average, 104 +/- 9.3 cases of mammary tumour were recorded at the Clinic of Obstetrics per year. This number did not increase after the Chernobyl atomic reactor catastrophe of 1986. The age distribution of canine mammary tumour found in this study shows good agreement with earlier data of the literature: mammary tumour showed the highest incidence in 10 years old dogs. The incidence of mammary tumour kept increasing with age until the 14th year of life (as expressed in per cent of animals of identical age). The number of mammary tumours was markedly higher in the spring (April-May) and autumn (September). This seasonality was demonstrable in 11 to 16 years old bitches, too. On the basis of the blood plasma E2 and P profiles, 61.5% of the clinically anoestrous animals were found to be cycling. The strikingly high ratio of pulis among dogs with mammary cancer was suggestive of a breed disposition. PMID:1476093

  9. Immunohistological assessment of fibrin deposition and thrombus formation in canine mammary neoplasia.

    PubMed

    Golombiewski, A; Gutberlet, K; Rudolph, R

    1997-08-01

    A commercially available monoclonal antibody against human fibrin was used to detect fibrin in canine formalin-fixed, paraffin wax-embedded tissue by applying a slightly modified alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. Twenty-eight mammary tumours from six bitches were examined for the presence of fibrin. Thrombi and extravascular fibrin deposits were detected in 15 tumours (12 complex adenocarcinomas, one adenocarcinoma, two solid carcinomas), and a single thrombus was detected in one adenoma; 12 tumours (three adenomas, one complex adenoma, four complex adenocarcinomas and four adenocarcinomas) did not show any staining reaction. PMID:9352443

  10. Mammary and extramammary Paget's disease*

    PubMed Central

    Lopes, Lauro Lourival; Lopes, Ione Maria Ribeiro Soares; Lopes, Lauro Rodolpho Soares; Enokihara, Milvia M. S. S.; Michalany, Alexandre Osores; Matsunaga, Nobuo

    2015-01-01

    Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent. PMID:25830993

  11. Mammary and extramammary Paget's disease.

    PubMed

    Lopes Filho, Lauro Lourival; Lopes, Ione Maria Ribeiro Soares; Lopes, Lauro Rodolpho Soares; Enokihara, Milvia M S S; Michalany, Alexandre Osores; Matsunaga, Nobuo

    2015-01-01

    Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent. PMID:25830993

  12. Expression of growth hormone in canine mammary tissue and mammary tumors. Evidence for a potential autocrine/paracrine stimulatory loop.

    PubMed Central

    van Garderen, E.; de Wit, M.; Voorhout, W. F.; Rutteman, G. R.; Mol, J. A.; Nederbragt, H.; Misdorp, W.

    1997-01-01

    The role of progestins in the pathogenesis of breast cancer in women remains controversial. To advance this discussion, we report the demonstration and localization of progestin-induced biosynthesis of growth hormone (GH) in canine mammary gland tissue. Nontumorous mammary tissues and tumors, both benign and malignant, were obtained from private household dogs. Immunoreactive GH was localized in mammary epithelial cells and correlated with the presence of GH mRNA. Local synthesis of GH was also proven immunoelectron microscopically by demonstrating GH-containing secretory granules. Cellular GH production in nontumorous tissues was more extensive during the progesterone-dominated luteal phase of the ovarian cycle or during exposure to synthetic progestins than during anestrus. GH was also associated with areas of hyperplastic mammary epithelium, which may indicate that locally produced GH enhances proliferation, acting in an autocrine and/or paracrine manner. In 41 of 44 tumors, GH was present. Of 3 GH-negative tumor samples, 2 were from progestin-depleted, castrated bitches. In nonmalignant mammary tissues, GH production is stimulated by progesterone and synthetic progestins interacting with progesterone receptors. In some progesterone-receptor-negative malignant tumors, GH expression was found, indicating loss of this control. Progestin-induced GH probably participates in the cyclic development of the mammary gland but may promote mammary tumorigenesis by stimulating proliferation of susceptible, and sometimes transformed, mammary epithelial cells. Images Figure 1 Figure 2 PMID:9060840

  13. Expression of growth hormone in canine mammary tissue and mammary tumors. Evidence for a potential autocrine/paracrine stimulatory loop.

    PubMed

    van Garderen, E; de Wit, M; Voorhout, W F; Rutteman, G R; Mol, J A; Nederbragt, H; Misdorp, W

    1997-03-01

    The role of progestins in the pathogenesis of breast cancer in women remains controversial. To advance this discussion, we report the demonstration and localization of progestin-induced biosynthesis of growth hormone (GH) in canine mammary gland tissue. Nontumorous mammary tissues and tumors, both benign and malignant, were obtained from private household dogs. Immunoreactive GH was localized in mammary epithelial cells and correlated with the presence of GH mRNA. Local synthesis of GH was also proven immunoelectron microscopically by demonstrating GH-containing secretory granules. Cellular GH production in nontumorous tissues was more extensive during the progesterone-dominated luteal phase of the ovarian cycle or during exposure to synthetic progestins than during anestrus. GH was also associated with areas of hyperplastic mammary epithelium, which may indicate that locally produced GH enhances proliferation, acting in an autocrine and/or paracrine manner. In 41 of 44 tumors, GH was present. Of 3 GH-negative tumor samples, 2 were from progestin-depleted, castrated bitches. In nonmalignant mammary tissues, GH production is stimulated by progesterone and synthetic progestins interacting with progesterone receptors. In some progesterone-receptor-negative malignant tumors, GH expression was found, indicating loss of this control. Progestin-induced GH probably participates in the cyclic development of the mammary gland but may promote mammary tumorigenesis by stimulating proliferation of susceptible, and sometimes transformed, mammary epithelial cells. PMID:9060840

  14. Increased expression of C5a receptor (CD88) mRNA in canine mammary tumors.

    PubMed

    Hezmee, Mohd Noor Mohd; Kyaw-Tanner, Myat; Lee, Jia Yu Peppermint; Shiels, Ian A; Rolfe, Barbara; Woodruff, Trent; Mills, Paul C

    2011-01-01

    Mammary tumors are among the most common neoplastic conditions in dogs, and there is evidence that inflammation plays a role in the development of some tumor types in dogs. The complement system is a major participant in the inflammatory process and the complement activation component, C5a, is a potent inflammatory peptide. This study investigated the mRNA expression of the major receptor for C5a (C5aR; CD88) in histopathological samples of canine mammary tumors by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using canine-specific primers for CD88. A total of seven canine mammary tumors (four malignant carcinomas, two benign mixed mammary tumors, and one myoepithelioma) and eight normal mammary glands were analysed. All the tumor samples expressed low levels of CD88 mRNA, while none of the normal mammary tissues showed any detectable expression. These preliminary results suggest that C5a-CD88 interaction may play a contributory role in the inflammatory response associated with mammary tumor development in dogs. Further studies investigating the mechanisms behind complement activation and C5a receptor expression in canine mammary tumors are warranted. PMID:20846729

  15. Mammary stem cell research in veterinary science: an update.

    PubMed

    Borena, Bizunesh M; Bussche, Leen; Burvenich, Christian; Duchateau, Luc; Van de Walle, Gerlinde R

    2013-06-15

    The mammary gland is an organ with a remarkable regenerative capacity that can undergo multiple cycles of proliferation, lactation, and involution. Growing evidence suggests that these changes are driven by the coordinated division and differentiation of mammary stem cell populations (MaSC). Whereas information regarding MaSC and their role in comparative mammary gland physiology is readily available in human and mice, such information remains scarce in most veterinary mammal species such as cows, horses, sheep, goats, pigs, and dogs. We believe that a better knowledge on the MaSC in these species will not only help to gain more insights into mammary gland (patho) physiology in veterinary medicine, but will also be of value for human medicine. Therefore, this review summarizes the current knowledge on stem cell isolation and characterization in different mammals of veterinary importance. PMID:23360296

  16. Use of tamoxifen in the control of canine mammary neoplasia.

    PubMed

    Morris, J S; Dobson, J M; Bostock, D E

    1993-11-27

    Ninety-three bitches which had undergone mammary tumour surgery were entered into a clinical trial to examine the effects of ovariohysterectomy (spaying) at the time of mammary surgery and the use of the drug tamoxifen in preventing the recurrence of the tumour and/or the development of new mammary tumours. Twenty-three of the bitches which had been spayed were allocated tamoxifen but only 18 of them complied with the treatment and in nine of these the treatment was stopped owing to side effects (mostly oestrogenic). Too few animals were studied to draw conclusions about the possible preventative effects of tamoxifen on mammary neoplasia, but the high percentage of bitches affected by oestrogen-like side effects may reduce the compliance of owners and prevent tamoxifen being widely used in dogs. PMID:8116156

  17. Comparative expression pathway analysis of human and canine mammary tumors

    PubMed Central

    Uva, Paolo; Aurisicchio, Luigi; Watters, James; Loboda, Andrey; Kulkarni, Amit; Castle, John; Palombo, Fabio; Viti, Valentina; Mesiti, Giuseppe; Zappulli, Valentina; Marconato, Laura; Abramo, Francesca; Ciliberto, Gennaro; Lahm, Armin; La Monica, Nicola; de Rinaldis, Emanuele

    2009-01-01

    Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies. PMID:19327144

  18. Correlation between histologic diagnosis mean nucleolar organizer region count and prognosis in canine mammary tumors.

    PubMed

    Bostock, D E; Moriarty, J; Crocker, J

    1992-09-01

    In this study, surgically excised mammary tumors from 98 bitches were graded histologically, and the grade was compared with the mean nucleolar organizer region (NOR) count in silver-stained paraffin-embedded sections. Histologically benign tumors, papillary adenocarcinomas, and intraductal carcinomas showed relatively little variation; the mean count for each category was between three and four NOR per nucleus. There was, however, a significant increase in the NOR counts in tubular and solid carcinomas. This increase was most pronounced for tumors that showed evidence of infiltration into the surrounding connective tissues. The mean NOR count for noninfiltrative carcinomas was 5.1, and that for invasive carcinomas was 7.3 (P less than 0.03). The mean NOR count for individual carcinomas ranged from 2.0 to 12.3, and a significant correlation was found between an increased NOR count and tumor-related death during the first post-surgical year. The 39 bitches in which the tumor had an NOR count less than 8.0 had a generally favorable prognosis; only six (15%) died as a result of the original neoplasm. In contrast, 18/21 dogs (85%) with a carcinoma having an NOR count greater than 8.0 died from the tumor during the first post-surgical year. A similar, although less pronounced result was obtained specifically for invasive carcinomas, in which 3/12 (25%) tumors with an NOR count less than 6.0 resulted in the death of the host, compared with 17/20 (85%) that had an NOR count greater than 6. By using this technique, it is possible to identify a subgroup of bitches with invasive mammary carcinomas that have a very poor prognosis following apparently adequate surgical ablation of the primary tumor. PMID:1413404

  19. Studies on acetyl-CoA carboxylase and fatty acid synthase from rat mammary gland and mammary tumours.

    PubMed Central

    Ahmad, P M; Feltman, D S; Ahmad, F

    1982-01-01

    The activities of two lipogenic enzymes, acetyl-CoA carboxylase and fatty acid synthase, were determined in two transplantable mammary adenocarcinomas (13762 and R3230AC) carried by non-pregnant, pregnant and lactating rats, and in mammary tissue of control animals (non-tumour-carrying) of comparable physiological states. During mammary-gland differentiation of control or tumour-carrying animals, the activities of acetyl-CoA carboxylase and fatty acid synthase in the lactating gland increased by about 40--50-fold over the values found in non-pregnant animals. On the other hand, in tumours carried by lactating dams there were only modest increases (1.5--2-fold) in acetyl-CoA carboxylase and fatty acid synthase compared with the neoplasms carried by non-pregnant animals. On the basis of the Km values for different substrates and immunodiffusion and immunotitration data, the fatty acid synthase of neoplastic tissues appeared to be indistinguishable from the control mammary-gland enzyme. However, a comparison of the immunotitration and immunodiffusion experiments indicated that the mammary-gland acetyl-CoA carboxylase might differ from the enzyme present in mammary neoplasms. Images Fig. 1. Fig. 2. PMID:6130760

  20. Aflatoxins ingestion and canine mammary tumors: There is an association?

    PubMed

    Frehse, M S; Martins, M I M; Ono, E Y S; Bracarense, A P F R L; Bissoqui, L Y; Teixeira, E M K; Santos, N J R; Freire, R L

    2015-10-01

    The aim of this study was to determine the presence of mycotoxins on dogs feed and to explore the potential association between mycotoxins exposure and the chance of mamary tumors in a case-control study. The study included 256 female dogs from a hospital population, 85 with mammary tumors (case group) and 171 without mammary tumors (control group). An epidemiological questionnaire was applied to both groups, and the data were analyzed by the EpiInfo statistical package. For the study, 168 samples of the feed offered to dogs were analyzed for the presence of aflatoxins, fumonisins and zearalenone by high-performance liquid chromatography. Mycotoxins were found in 79 samples (100%) in the case group and 87/89 (97.8%) in the control group. Mycotoxins were detected in all types of feed, regardless feed quality. Level of aflatoxin B1 (p = 0.0356, OR = 2.74, 95%, CI 1.13 to 6.60), aflatoxin G1 (AFG1) (p = 0.00007, OR = 4.60, 95%, CI = 2.16 to 9.79), and aflatoxin G2 (AFG2) (p = 0.0133, OR = 9.91, 95%, CI 1.21 to 81.15) were statistically higher in case of mammary cancer. In contrast, neutering was a protective factor for mammary cancer (p = 0.0004, OR = 0.32, 95%, CI = 0.17 to 0.60). PMID:26271706

  1. [Hormones and mammary tumors in the bitch: a review].

    PubMed

    Rutteman, G R

    1992-02-01

    Toxicity studies as well as epidemiological studies in veterinary medicine have shown that both ovarian steroids and a large number of synthetic derivatives may promote the formation of mammary tumours in dogs. Abnormalities in pituitary function, particularly in the secretion of growth hormones, have been assumed to be involved in this process. In the present paper the possible role of endogenous and exogenous hormones in the pathogenesis of mammary tumours in bitches is reviewed. The available evidence suggests that steroid hormones may act at an early stage in the development of tumours by stimulating the proliferation of normal epithelium. This results in an increase in the number of susceptible cells. In addition a growth-stimulating action may be exerted upon cells which have undergone partial malignant transformation, but possibly to a lesser extent upon fully malignant cells at a late stage of tumour development. In advanced mammary cancers steroid receptors are frequently absent, which may indicate a more autonomous pattern of growth. It seems justified to conclude that in clinical practice ovariectomy at an early age as a measure to prevent oestrus is to be preferred to progestin treatment with regard to the risk of mammary carcinoma. Still, there is no indication that in dogs, ovariectomy will reduce the risk of metastasis once the animal is presented with a mammary carcinoma. The earlier assumption that overproduction of growth hormone is an important factor in the pathogenesis of spontaneous mammary tumours in the dogs could not be proven. The role of prolactin and of thyroid hormones in this process continues to be uncertain. PMID:1736405

  2. [Dog bites].

    PubMed

    Horn, Benedikt

    2015-01-01

    In Switzerland 10'000 people are bitten by a dog annualy. Dog bites are notifiable incidents. Defensive and offensive aggression of dogs (why does a dog bite?), history, signs, treatment and prevention are discussed. Finally a short psychogram of dog owner and victim emphasizes the role of avoiding any escalation. PMID:25533260

  3. Investigation of HER2 expression in canine mammary tumors by antibody-based, transcriptomic and mass spectrometry analysis: is the dog a suitable animal model for human breast cancer?

    PubMed

    Burrai, G P; Tanca, A; De Miglio, M R; Abbondio, M; Pisanu, S; Polinas, M; Pirino, S; Mohammed, S I; Uzzau, S; Addis, M F; Antuofermo, E

    2015-11-01

    Canine mammary tumors (CMTs) share many features with human breast cancer (HBC), specifically concerning cancer-related pathways. Although the human epidermal growth factor receptor 2 (HER2) plays a significant role as a therapeutic and prognostic biomarker in HBC, its relevance in the pathogenesis and prognosis of CMT is still controversial. The aim of this study was to investigate HER2 expression in canine mammary hyperplasic and neoplastic tissues as well as to evaluate the specificity of the most commonly used polyclonal anti HER2 antibody by multiple molecular approaches. HER2 protein and RNA expression were determined by immunohistochemistry (IHC) and by quantitative real-time (qRT) PCR. A strong cell membrane associated with non-specific cytoplasmic staining was observed in 22% of carcinomas by IHC. Adenomas and carcinomas exhibited a significantly higher HER2 mRNA expression when compared to normal mammary glands, although no significant difference between benign and malignant tumors was noticed by qRT-PCR. The IHC results suggest a lack of specificity of the FDA-approved antibody in CMT samples as further demonstrated by Western immunoblotting (WB) and reverse phase protein arrays (RPPA). Furthemore, HER2 was not detected by mass spectrometry (MS) in a protein-expressing carcinoma at the IHC investigation. This study highlights that caution needs to be used when trying to translate from human to veterinary medicine information concerning cancer-related biomarkers and pathways. Further investigations are necessary to carefully assess the diagnostic and biological role specifically exerted by HER2 in CMTs and the use of canine mammary tumors as a model of HER2 over-expressing breast cancer. PMID:26088453

  4. Influence of ovariectomy at the time of mastectomy on the prognosis for canine malignant mammary tumours.

    PubMed

    Yamagami, T; Kobayashi, T; Takahashi, K; Sugiyama, M

    1996-10-01

    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. PMID:8912239

  5. Synchronous ipsilateral carcinoma of the accessory mammary gland and primary lymphoma of the breast with subsequent rectal carcinoma: report of a case.

    PubMed

    Nishikawa, Akihiro; Kasai, Hide; Koyama, Yoshinori; Koide, Naohiko; Iijima, Akihiro; Shimojo, Hisashi; Kumeda, Shigeyoshi

    2014-01-01

    A case of synchronous carcinoma of the accessory mammary gland and primary breast lymphoma with subsequent rectal carcinoma has not been reported previously. We present a very rare case of primary non-Hodgkin lymphoma of the left breast diagnosed simultaneously with invasive lobular carcinoma of the left axillary accessory mammary gland and rectal adenocarcinoma. An 82-year-old Japanese woman presented with two palpable masses on the left chest wall. She was given a diagnosis of suspected breast malignant tumor and axillary accessory mammary gland. She underwent excision of the axillary accessory mammary gland and left mastectomy with axillary lymph node dissection. Histopathological examination revealed diffuse large B-cell lymphoma of the breast and invasive lobular carcinoma of the axillary accessory mammary gland with lymph nodes metastasis. Three months after the surgery, primary rectal adenocarcinoma was also detected by F-18 fluorodeoxyglucose positron emission tomography. Hartmann's operation was performed, since which time the patient has been doing well. PMID:25217973

  6. Xenobiotic-metabolizing enzymes in canine mammary tumours.

    PubMed

    Kumaraguruparan, R; Subapriya, R; Balachandran, C; Manohar, B Murali; Thangadurai, A; Nagini, S

    2006-09-01

    Mammary tumours are the most common neoplasms in female dogs. The present study was designed to evaluate the relationship between different clinical stages with activities of phase I and phase II carcinogen-metabolizing enzymes in canine mammary tumours. The levels of cytochrome P450 and cytochrome b5 and the activities of glutathione S-transferase (GST), gamma-glutamyl transpeptidase (GGT), DT-diaphorase (DTD) and NADPH diaphorase in tumour tissues of 25 bitches was estimated. Enhanced levels of cytochrome P450 and b5 and phase II enzyme activities were observed in tumour tissues compared to the corresponding uninvolved adjacent tissues. The magnitude of the changes in phase I and phase II enzyme status was, however, more pronounced in stages I and II compared to stages III and IV. The results suggest that the balance between phase I carcinogen activation and phase II detoxification systems may play an important role in canine mammary tumour development. PMID:16014333

  7. /sup 20/neon ion- and x-ray-induced mammary carcinogenesis in female rats

    SciTech Connect

    Shellabarger, C.J.; Baum, J.W.; Holtzman, S.; Stone, J.P.

    1983-01-01

    One of the proposed uses of heavy ion irradiation is to image lesions of the human female breast. The rat model system was chosen to assess the carcinogenic potential of heavy ion irradiation in the belief that data obtained from rat studies would have a qualitatively predictive value for the human female. Accordingly, female rats were exposed to /sup 20/Ne ions at the BEVALAC and studied for the development of mammary neoplasia for 312 +- 2 days at Brookhaven along with rats exposed concurrently to x-irradiation or to no irradiation. As the dose of either type of radiation was increased the percent of rats with mammary adenocarcinomas, and the percent of rats with mammary fibroadenomas, tended to increase. At a prevalence of 20%, the RBE for /sup 20/Neon ions for mammary adenocarcinomas was estimated to be larger than 5 and for mammary fibroadenomas the RBE was estimated to be less than 2. No conclusion was reached concerning whether or not the RBE might vary with dose. We suggest that /sup 20/Ne ions do have a carcinogenic potential for rat mammary tissue and that this carcinogenic potential is likely to be greater than for x-irradiation. (DT)

  8. Mammary cancers and pregnancy.

    PubMed Central

    Anderson, J M

    1979-01-01

    Uncertainties persist about management and prognosis of mammary cancers that occur during and after pregnancy and during lactation. Pathological features of mammary cancers occurring during pregnancy are the same as those in non-pregnant women and survival rates are comparable. Management should be the same as in non-pregnant patients. Termination of pregnancy does not improve survival but it should be advised if the prognosis is poor. Mastectomy apparently presents little danger to the fetus, though treatment such as chemotherapy and irradiation should be avoided. Women who have received treatment for mammary cancer need not be advised against subsequent pregnancy. Routine ovarian radiation in non-pregnant premenopausal women is not generally to be recommended, since it does not prolong survival and would deprive some of the chance of further pregnancy. In lactating women who develop mammary cancers survival is apparently not adversely affected. Lactation should be suppressed initially and followed by mastectomy. Regimens of immunotherapy, chemotherapy, or radiotherapy may then be begun. Until results of current trials of combined treatments of mammary cancers associated with pregnancy are available, management should be neither aggressive nor tentative. It should be based on a well-balanced concept of applying all available treatments, as in non-pregnant patients. PMID:376044

  9. Activation of Mammalian target of rapamycin in canine mammary carcinomas: an immunohistochemical study.

    PubMed

    Delgado, L; Gärtner, F; Dias Pereira, P

    2015-01-01

    Mammalian target of rapamycin (mTOR) is a serine-threonine kinase involved in cell growth, proliferation and survival. Activation of mTOR has been reported in various tumour types, including human breast cancer; however, the expression of mTOR in canine mammary tumours has not been examined. In the present study, expression of the activated form of mTOR (phospho-mTOR [p-mTOR]) was examined immunohistochemically in five normal canine mammary glands, 45 canine mammary carcinomas and their corresponding metastatic lesions (n = 15). Phospho-mTOR was not expressed in normal canine mammary tissue, but cytoplasmic labelling was observed in 78% of canine mammary carcinomas. Two carcinomas had both cytoplasmic and nuclear labelling. No significant relationship was found between p-mTOR cytoplasmic expression and histological type or grading of carcinomas, degree of tubular formation, anisokaryosis, mitotic activity or lymph node metastasis. In all except one case, the expression pattern of p-mTOR in lymph node metastases was similar or decreased when compared with the primary lesion. The findings suggest that p-mTOR is involved in mammary carcinogenesis in dogs. However, p-mTOR cytoplasmic expression does not appear to be a prognostic indicator in canine mammary carcinomas, which may be related to its subcellular location in the neoplastic cells. Canine mammary tumours may provide a model for the development of innovative medical strategies involving mTOR inhibitors in human breast cancer. PMID:25670666

  10. Influence of catechol-O-methyltransferase (COMT) genotypes on the prognosis of canine mammary tumors.

    PubMed

    Dias Pereira, P; Lopes, C C; Matos, A J F; Pinto, D; Gärtner, F; Lopes, C; Medeiros, R

    2009-11-01

    Catechol-O-methyltransferase (COMT) is an important enzyme involved in inactivation of catechol estrogens, which are metabolites with carcinogenic properties. Some investigations in human breast cancer associate a genetic polymorphism in the COMT gene (COMT val158met) with an increased risk and poor clinical progression of the disease. In dogs, there are 2 recognized single nucleotide polymorphisms in the COMT gene (COMTG216A and COMTG482A); however, their influence on the outcome of mammary neoplasms has never been investigated. The purpose of this study is to investigate the influence of COMT in the clinical progression of canine mammary tumors, namely in recurrence, metastasis and survival by testing 2 SNPs (G216A and G482A), and 2 genotypes of the COMT gene. A case series was conducted analyzing genomic DNA samples by polymerase chain reaction-restriction fragment length polymorphism from 80 bitches with mammary tumors. Animals were submitted to an active follow-up study for a period of 24 months after surgery. We observed that bitches carrying both genetic variations simultaneously are more likely to develop recurrence of mammary lesions. Our results demonstrate a possible role for COMT genotypes in the outcome of mammary neoplasms in the dog. Identifying a genetic factor predictive of recurrence may be useful in selecting the most effective surgical approach for canine mammary neoplasms. PMID:19605895

  11. Cytological study on the anterior pituitary of senile untreated beagle bitches with spontaneous mammary tumours.

    PubMed

    Attia, M A

    1982-05-01

    Pituitaries were obtained from senile untreated Beagle bitches of comparable age (7-9 years) and genital status. The animals were divided into three groups; one was normal (without mammary lesions), one had benign tumours and one had mammary adenocarcinomas. PRL-, STH-, ACTH- and gonadotrophin-producing cells are studied and counted in serial paraffin sections stained with histochemical techniques. The animals with mammary malignancy displayed a marked increase in the relative number of PRL and ACTH cells with morphological signs of higher secretory activity in most cells, compared with that in normal bitches or bitches with benign tumours. STH cells in bitches with adenocarcinomas were reduced in number; however the secretory activity in these animals was the same as that observed in the normal bitches. In the animals with benign mammary tumours, STH cells showed morphological indication of higher secretory activity than in the other groups. PRL and ACTH cells were slightly increased in number and had slightly higher activity than that in normal bitches. These findings may suggest a role for hypophyseal hormones in mammary neoplasias. PMID:6287969

  12. Mammary Glands: Developmental Changes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mammary gland progresses from the accumulation of a few cells in the embryonic ectoderm to a highly arborescent tubulo-alveolar gland capable of secreting a highly nutritious product for consumption. Throughout this progression, various changes occur during each developmental stage: prenatal, pr...

  13. Prognostic value of vascular endothelial growth factor and hypoxia-inducible factor 1α in canine malignant mammary tumors.

    PubMed

    Moschetta, Marina Gobbe; Maschio, Larissa Bazela; Jardim-Perassi, Bruna Victorasso; Gelaleti, Gabriela Bottaro; Lopes, Juliana Ramos; Leonel, Camila; Gonçalves, Naiane Do Nascimento; Ferreira, Lívia Carvalho; Martins, Gustavo Rodrigues; Borin, Thaiz Ferraz; Zuccari, Debora Aparecida Pires De Campos

    2015-05-01

    Mammary tumors are the most common type of tumor in dogs, with approximately half of these tumors being malignant. Hypoxia, characterized by oxygen levels below normal, is a known adverse factor to cancer treatment. The hypoxia-inducible factor 1α (HIF-1α) is a central regulator of the pathophysiological response of mammalian cells to low oxygen levels. HIF-1α activates the transcription of vascular endothelial growth factor (VEGF), which in turn promotes angiogenesis through its ability to stimulate the growth, migration and invasion of endothelial cells to form new blood vessels, contributing to tumor progression. In this study, we evaluated the serum concentration and gene expression of VEGF and HIF-1α linking them with clinicopathological parameters and survival of dogs with mammary tumors in order to infer the possible prognostic value of these factors. We collected blood and tumor fragments of 24 female dogs with malignant mammary tumors (study group) and 26 non-affected female dogs (control group) to verify the gene expression of VEGF and HIF-1α by quantitative real-time PCR (qPCR) and the serum levels by ELISA (enzyme-linked immunosorbent). The results showed high serum levels of VEGF in the study group and its correlation between abundant vascularization, lymph node involvement, metastasis, death rate and low survival (p<0.05). The serum percentage of HIF-1α in female dogs with mammary neoplasia was lower than that in the control group and higher in female dogs with tumor metastasis and history of tumor recurrence (p<0.05). Regarding gene expression, there was a gene overexpression of VEGFA in female dogs with poor outcome, in contrast to the gene underexpression of HIF-1A. Taken together, these results suggested that VEGF is important in tumor progression and can be used as a potential prognostic marker in the clinic and may be useful in predicting tumor progression in dogs with mammary neoplasia. PMID:25779537

  14. Induction of mammary tumors in virgin female BALB/c mice by single low doses of 7,12-dimethylbenz(a)anthracene

    SciTech Connect

    Ethier, S.P.; Ullrich, R.L.

    1982-11-01

    The induction of mammary tumors in virgin female inbred BALB/c mice after administration of 7,12-dimethylbenz(a)anthracene (DMBA) over a wide range of doses was studied. Mice were exposed at 12 weeks of age to single or multiple doses of DMBA ranging from 0.0025 to 12.0 mg by gastric intubation and were checked regularly for mammary tumors. The experiment was terminated when the mice were 800 days of age. In the dose range of 0.0025-0.125 mg DMBA, the incidence of mammary tumors was dose-dependent. At higher doses, the mammary tumor incidence became less dose-dependent and was nearly independent of doses above the 0.25-mg level. Analysis of the data for the rate of appearance of mammary tumor with age of the animals and for the age at death of non-mammary tumor-bearing animals indicated that in the low dose range induction of mammary tumors was the predominant effect of DMBA exposure, whereas at moderate to high doses the toxic and carcinogenic effects of DMBA on other tissues significantly influenced the final incidence of mammary tumors. Greater than 90% of the tumors that resulted from administration of low doses of DMBA were adenocarcinomas. In contrast, adenocarcinomas and adenoacanthomas were found in approximately equal proportions following administration of high doses of DMBA.

  15. Estrogens metabolism associated with polymorphisms: influence of COMT G482a genotype on age at onset of canine mammary tumors.

    PubMed

    Dias Pereira, P; Lopes, C C; Matos, A J F; Pinto, D; Gärtner, F; Lopes, C; Medeiros, R

    2008-03-01

    Catechol-O-methyltransferase (COMT) is an important enzyme participating in inactivation of carcinogenic oestrogen metabolites. In humans there is a single nucleotide polymorphism in COMT gene (COMT val158met) that has been associated with an increased risk for developing breast cancer. In dogs, there is a single nucleotide polymorphism in COMT gene (G482A), but its relation with mammary carcinogenesis has never been investigated. The aim of this study was to focus on the evaluation of such polymorphism as a risk factor for the development of mammary tumors in bitches and on the analysis of its relationship with some clinicopathologic features (dog's age and weight, number and histologic type of the lesions, lymph node metastasis) of canine mammary neoplasms. A case-control study was conducted analyzing 90 bitches with mammary tumors and 84 bitches without evidence of neoplastic disease. The COMT G482A polymorphism was analyzed by PCR-RFLP. We found a protective effect of the polymorphism in age of onset of mammary tumors, although we could not establish a significant association between COMT genotype and other clinicopathologic parameters nor with mammary tumor risk overall. Animals carrying the variant allele have a threefold likelihood of developing mammary tumors after 9 years of age in comparison with noncarriers. The Kaplan-Meier method revealed significant differences in the waiting time for onset of malignant disease for A allele carrier (12.46 years) and noncarrier (11.13 years) animals. This investigation constitutes the first case-control study designed to assess the relationship between polymorphic genes and mammary tumor risk in dogs. Our results point to the combined effect of COMT genotype with other genetic and/or environmental risk factors as important key factors for mammary tumor etiopathogenesis. PMID:18424824

  16. Expression of different phenotypes in cell lines from canine mammary spindle-cell tumours and osteosarcomas indicating a pluripotent mammary stem cell origin.

    PubMed

    Hellmén, E; Moller, M; Blankenstein, M A; Andersson, L; Westermark, B

    2000-06-01

    Mammary spindle-cell tumours and sarcomas seem to be restricted to dogs and humans. Two cell lines from spontaneous primary canine mammary spindle-cell tumours (CMT-U304 and CMT-U309) and two cell lines from spontaneous primary canine mammary osteosarcomas (CMT-U334 and CMT-U335) were established to study the mesenchymal phenotypes of mammary tumours in the female dog. The cells from the spindle-cell tumours expressed cytokeratin, vimentin and smooth muscle actin filaments. When these cells were inoculated subcutaneously into female and male nude mice they formed different types of mesenchymal tumours such as spindle-cell tumours, fibroma and rhabdomyoid tumours (n = 6/8). The cells from the osteosarcomas expressed vimentin filaments and also formed different types of mesenchymal tumours such as chondroid, rhabdomyoid, smooth muscle-like and spindle-cell tumours (n = 6/10). The cell lines CMT-U304, CMT-U309 and CMT-U335 had receptors for progesterone but none of the four cell lines had receptors for estrogen. All four cell lines and their corresponding primary tumours showed identical allelic patterns in microsatellite analysis. By in situ hybridization with genomic DNA we could verify that all formed tumours but one were of canine origin. Our results support the hypothesis that canine mammary tumours are derived from pluripotent stem cells. PMID:10965996

  17. Expression and role of PGP, BCRP, MRP1 and MRP3 in multidrug resistance of canine mammary cancer cells

    PubMed Central

    2013-01-01

    Background In both women and female dogs, the most prevalent type of malignant neoplasm is the spontaneous mammary tumor. In dogs, half of these are malignant. The treatment of choice for the canine patients is surgical mastectomy. Unfortunately, it often fails in high-risk, locally invasive mammary tumors as of during the time of the surgery the micro-metastases are present. Moreover, there are neither large studies conducting to prove of the benefit from the chemotherapy in dogs nor established chemotherapy treatment protocols available. Additionally, the effectiveness of each individual chemotherapeutic agent and drug resistance of canine mammary cancer have not yet been characterized. That has become the aim of our study, to assess the expression of PGP, BCRP, MRP1 and MRP3 in canine mammary cancer cell lines and to investigate their role in cancer resistance to vinblastine, cisplatin and cyclophosphamide with using RNAi approach. Results The results suggested that in canine mammary cancer, the vinblastine efflux was mediated by PGP and MRP1 proteins, cisplatin efflux was mediated by all four examined efflux pumps (PGP, BCRP, MRP1 and MRP3), whereas cyclophosphamide resistance was related to BCRP activity. RNAi silencing of these efflux pumps significantly decreased IC50 doses of the examined drugs in canine mammary carcinoma cells. Conclusions Our results have indicated the treatment of cells involving use of the siRNA targeting efflux pumps could be a beneficial approach in the future. PMID:23773525

  18. Prognostic factors in canine mammary cancer.

    PubMed

    Misdorp, W; Hart, A A

    1976-04-01

    From a follow-up study of dogs surgically treated for mammary cancer, ten characteristics were analyzed statistically with special reference to their association with prognosis (expressed as survival for 2 years). The interrelations among five of the characteristics were also tested. The histologic type (descending range in malignancy: sarcomas greater than simple carcinomas greater than complex carcinomas), mode of growth (highly infiltrating greater than moderately infiltrating greater than expansive), clinical stage of complex carcinomas (large tumors and/or tumors involving the skin or underlying tissue greater than small, well-defined tumors), and size (greater than 15 cm greater than 11-15 cm greater than 5-10 cm greater than 0-5 cm) were of definite prognostic importance. The histologic grade was of possible prognostic importance. Localization, type of surgical therapy (mastectomy, block-dissection), growth in lymph vessels, involvement of regional lymph nodes, and duration of symptoms before treatment were not important to prognosis. A comparison between the factors associated with the prognosis of canine and human mammary cancer showed many similarities. However, the involvement of regional lymph nodes, important in women, was not so in bitches. PMID:1255797

  19. Positive correlation of steroid hormones and EGF in canine mammary cancer.

    PubMed

    Queiroga, Felisbina L; Pérez-Alenza, Dolores; Silvan, Gema; Peña, Laura; Illera, Juan C

    2009-05-01

    There are no published studies focused on the potential crosstalk between steroid hormones and EGF in canine mammary tumourigenesis. The objective was to investigate the role of EGF in canine mammary tumours (CMT) and the relationship with steroid hormones. Sixty-three CMT (39 malignant including 10 inflammatory mammary carcinomas (IMC); 19 benign and 5 dysplasias), and 13 normal mammary glands from dogs without history of neoplastic disease were analysed. Levels of EGF and steroid hormones [progesterone (P4); 17beta-estradiol (E2); androstenedione (A4) and dehydroepiandrosterone (DHEA)], were analysed by EIA in CMT homogenates. Levels of EGF were significantly higher in malignant compared with benign tumours, dysplasias and normal mammary glands (p<0.001). IMC presented the highest EGF levels, with statistical significant difference between IMC and non-IMC cases (p<0.05). Steroid hormone levels were also significantly higher in malignant tumours compared with benign tumours, dysplasias and normal mammary glands (p<0.001). In malignant tumours (non-IMC and IMC), a strong correlation was observed between EGF and: P4 (r=0.452; p=0.003); E2 (r=0.624; p=0.023); A4 (r=0.496; p=0.038); DHEA (r=0.431; p=0.005). These results suggest that EGF is implicated in canine mammary tumourigenesis. The positive correlation observed, opens an interesting perspective of interaction that should be further investigated. PMID:19429455

  20. Breed-Predispositions to Cancer in Pedigree Dogs

    PubMed Central

    Dobson, Jane M.

    2013-01-01

    Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared to humans, and by using newly developed resources, genome-wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders. This paper will review the literature on canine breed susceptibility to histiocytic sarcoma, osteosarcoma, haemangiosarcoma, mast cell tumours, lymphoma, melanoma, and mammary tumours including the recent advances in knowledge through molecular genetic, cytogenetic, and genome wide association studies. PMID:23738139

  1. Breed-predispositions to cancer in pedigree dogs.

    PubMed

    Dobson, Jane M

    2013-01-01

    Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared to humans, and by using newly developed resources, genome-wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders. This paper will review the literature on canine breed susceptibility to histiocytic sarcoma, osteosarcoma, haemangiosarcoma, mast cell tumours, lymphoma, melanoma, and mammary tumours including the recent advances in knowledge through molecular genetic, cytogenetic, and genome wide association studies. PMID:23738139

  2. Significance of rat mammary tumors for human risk assessment.

    PubMed

    Russo, Jose

    2015-02-01

    We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine the response of the tumors induced to chemotherapy. The utilization of experimental models of mammary carcinogenesis in risk assessment requires that the influence of ovarian, pituitary, and placental hormones, among others, as well as overall reproductive events are taken into consideration, since they are important modifiers of the susceptibility of the organ to neoplastic development. Several species, such as rodents, dogs, cats, and monkeys, have been evaluated for these purposes; however, none of them fulfills all the criteria specified previously. Rodents, however, are the most widely used models; therefore, this work will concentrate on discussing the rat rodent model of mammary carcinogenesis. PMID:25714400

  3. Metastatic, papillary cystadenocarcinoma of the mammary gland in a black-footed ferret

    USGS Publications Warehouse

    Carpenter, J.W.; Davidson, J.P.; Novilla, M.N.; Huang, J.C.M.

    1980-01-01

    A simple, papillary cystic adenocarcinoma of the mammary gland with metastases to the internal iliac and mesenteric lymph nodes, liver, and spleen was observed in a 12 to 13 year old female black-footed ferret (Mustela nigripes). Histologically, the tumor was aggressive, and lymphatic invasion was found. Attempts at virus isolation were negative. Other findings were bilateral infarcts in the kidneys, apparently resulting in acute renal shutdown and death, multiple thrombi in the right atrium, aortic arteriosclerosis, and focal interstitial pneumonia.

  4. Endocrine diseases in dogs and cats: similarities and differences with endocrine diseases in humans.

    PubMed

    Rijnberk, Ad; Kooistra, Hans S; Mol, Jan A

    2003-08-01

    Over several millennia, humans have created hundreds of dog and cat breeds by selective breeding, including fixation of mutant genes. The domestic dog is unique in the extent of its variation in height, weight and shape as well as its behavior. It is primarily the relatively long persistence of high levels of growth hormone (GH) release at a young age that accounts for the large body size in giant breeds of dogs. Several of the endocrine diseases of humans are also known to occur as similar entities in dogs and cats. With some variations, this is true for conditions such as diabetes mellitus and the hypofunction syndromes of the thyroid and adrenal cortex. Also, the hyperfunction syndromes of hypercortisolism and hyperparathyroidism in dogs and cats have many similarities with their human counterparts. The exception seems to be Graves' disease. This condition, which is due to production of thyroid-stimulating hormone (TSH)-receptor antibodies, has not been observed in dogs and cats. The very common form of hyperthyroidism in cats is due to toxic adenomas. In the 1980s it was discovered that in dogs exogenous progestins and endogenous progesterone can induce GH excess. This GH excess originates form the mammary gland and may give rise to acromegaly and insulin resistance. GH production by the mammary gland is not unique to the dog. It has become clear that cats and humans also express the GH gene in the mammary gland. There is increasing evidence that this locally produced GH not only plays a role in the morphologic changes of the mammary gland associated with the ovarian cycle and gestation, but that it is also involved in the development of breast cancer. In dogs, induction of mammary GH production by progestin administration allows for treatment of GH deficiency. PMID:12914747

  5. Male breast cancer originating in an accessory mammary gland in the axilla: a case report.

    PubMed

    Yamamura, Jun; Masuda, Norikazu; Kodama, Yoshinori; Yasojima, Hiroyuki; Mizutani, Makiko; Kuriyama, Keiko; Mano, Masayuki; Nakamori, Shoji; Sekimoto, Mitsugu

    2012-01-01

    Carcinoma of an accessory mammary gland is an extremely rare tumor. A 61-year-old male patient presented with a hard mass measuring 85 mm × 51 mm in the left axilla. Incisional biopsy histopathologically showed an adenocarcinoma compatible with breast carcinoma originating in an accessory mammary gland. Systemic examinations revealed no evidence of malignant or occult primary lesion in the bilateral mammary glands or in other organs. Neoadjuvant chemotherapy was performed for the locally advanced axillary tumor and reduced the tumor to 55 mm in size, and, then, he could undergo complete resection with a negative surgical margin in combination with reconstructive surgery to fill the resulting skin defect with a local flap of the latissimus dorsi muscle. The patient has presented with no metastatic lesion in four years since the operation. This unusual case shows that neoadjuvant chemotherapy is an effective and tolerated therapy for advanced accessory breast cancer in the axilla. PMID:23251170

  6. Adjuvant therapy for highly malignant canine mammary tumours: Cox-2 inhibitor versus chemotherapy: a case-control prospective study.

    PubMed

    Arenas, C; Peña, L; Granados-Soler, J L; Pérez-Alenza, M D

    2016-07-30

    Cyclooxygenase-2 (Cox-2) enzyme participates in different steps of the carcinogenetic process and in canine mammary tumours (CMTs), a high expression of Cox-2 is associated with malignancy and tumour angiogenesis. The objectives of the study were to evaluate the disease-free survival (DFS) and overall survival (OS) of a Cox-2 inhibitor as adjuvant therapy in dogs with highly malignant (HM)-CMTs and compare it with that of dogs treated with chemotherapy and with control dogs. Twenty-eight dogs were prospectively included. After surgery, dogs were alternatively allocated into two treatment groups (chemotherapy with mitoxantrone n=8; Cox-2 inhibitor, firocoxib n=7). Control group (n=13) included dogs whose owners rejected adjuvant therapy. All dogs were followed up for two years or until death. The DFS was significantly higher in dogs that received adjuvant treatment (mitoxantrone or firocoxib) (P=0.030) than in control dogs. Dogs on firocoxib treatment had significantly higher DFS (P=0.015) and OS (P=0.048) than control dogs. The DFS and OS of dogs on mitoxantrone treatment were not statistically different from controls. In conclusion, this study supports the use of firocoxib for the treatment of HM-CMTs. Further studies are needed to compare the efficacy of chemotherapy drugs versus Cox-2 inhibitors as adjuvant treatment in these cases. PMID:27377395

  7. Solid adenocarcinoma

    Cancer.gov

    Uniformly solid character of the lesions is usually indicative of a well differentiated tumor. No solid adenocarcinomas have observed in our series. However, rare cases have been described by others. In human pathology this diagnosis is usually based on detection of mucin after periodic acid-Schiff reaction with diastase (α-amylase) digestion.

  8. Clinical and prognostic implications of serum and tissue prolactin levels in canine mammary tumours.

    PubMed

    Queiroga, F L; Pérez-Alenza, M D; González Gil, A; Silvan, G; Peña, L; Illera, J C

    2014-10-25

    The biological implications of serum and tissue prolactin levels in canine mammary tumours (CMT) have been previously described although the influence of this hormone on inflammatory mammary carcinomas as well as its value as prognostic indicator remains to be properly clarified. Prolactin determinations were carried out by enzyme immunoassay in tumour tissue and serum of 39 female dogs with spontaneous CMT and in normal mammary gland and serum of 10 controls. Prolactin levels were higher in the case of CMT compared to controls (P<0.05). In malignant CMT, higher levels of tissue prolactin were associated with the occurrence of tumour relapse and/or distant metastasis (P<0.05). Inflammatory mammary carcinomas presented the highest values for tissue prolactin concentrations with concentrations significantly higher than other malignant non-inflammatory mammary carcinoma tumours (P<0.05). The high levels of prolactin found in cases with poor clinical prognoses, including inflammatory mammary carcinoma, open the possibility of being able to better stratify clinical cases in malignant CMT with a view to tailoring treatment appropriately. PMID:25096592

  9. Canine Mammary Tumours Are Affected by Frequent Copy Number Aberrations, including Amplification of MYC and Loss of PTEN

    PubMed Central

    Borge, Kaja S.; Nord, Silje; Van Loo, Peter; Lingjærde, Ole C.; Gunnes, Gjermund; Alnæs, Grethe I. G.; Solvang, Hiroko K.; Lüders, Torben; Kristensen, Vessela N.; Børresen-Dale, Anne-Lise; Lingaas, Frode

    2015-01-01

    Background Copy number aberrations frequently occur during the development of many cancers. Such events affect dosage of involved genes and may cause further genomic instability and progression of cancer. In this survey, canine SNP microarrays were used to study 117 canine mammary tumours from 69 dogs. Results We found a high occurrence of copy number aberrations in canine mammary tumours, losses being more frequent than gains. Increased frequency of aberrations and loss of heterozygosity were positively correlated with increased malignancy in terms of histopathological diagnosis. One of the most highly recurrently amplified regions harbored the MYC gene. PTEN was located to a frequently lost region and also homozygously deleted in five tumours. Thus, deregulation of these genes due to copy number aberrations appears to be an important event in canine mammary tumour development. Other potential contributors to canine mammary tumour pathogenesis are COL9A3, INPP5A, CYP2E1 and RB1. The present study also shows that a more detailed analysis of chromosomal aberrations associated with histopathological parameters may aid in identifying specific genes associated with canine mammary tumour progression. Conclusions The high frequency of copy number aberrations is a prominent feature of canine mammary tumours as seen in other canine and human cancers. Our findings share several features with corresponding studies in human breast tumours and strengthen the dog as a suitable model organism for this disease. PMID:25955013

  10. Expression of tissue factor in canine mammary tumours and correlation with grade, stage and markers of haemostasis and inflammation.

    PubMed

    Andreasen, E B; Nielsen, O L; Tranholm, M; Knudsen, T; Kristensen, A T

    2016-06-01

    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). PMID:24674618

  11. Mammary tumors and serum hormones in the bitch treated with medroxyprogesterone acetate or progesterone for four years.

    PubMed

    Frank, D W; Kirton, K T; Murchison, T E; Quinlan, W J; Coleman, M E; Gilbertson, T J; Feenstra, E S; Kimball, F A

    1979-03-01

    After 4 years of a long-term contraceptive steroid safety study, the incidence and the histologic types of mammary dysplasia produced are shown to be similar in beagles treated with medroxyprogesterone acetate (medroxyprogesterone) or progesterone. Serum insulin, thyroid-stimulating hormone (TSH), triiodothyronine, growth hormone, prolactin, 17 beta-estradiol, progesterone, and cortisol were determined by radioimmunoassay on samples collected after 45 months of treatment. Serum growth hormone and insulin concentrations were elevated in a dose-related manner in both treatment groups. Levels of triiodothyronine, cortisol, and 17 beta-estradiol (medroxyprogesterone only) were lowered. TSH and prolactin concentrations were not changed. Pituitary-gonadal hormone interaction in the pathogenesis of mammary neoplasia of the dog is discussed. Prolonged treatment of beagles with doses of progesterone or medroxyprogesterone 1 to 25 times the human contraceptive dose or luteal phase (dog) levels, respectively, results in a dose-related incidence of mammary nodules. PMID:437169

  12. Altered oxidant-antioxidant profile in canine mammary tumours.

    PubMed

    Kumaraguruparan, R; Balachandran, C; Manohar, B Murali; Nagini, S

    2005-05-01

    Mammary tumours are the most common neoplasms in female dogs. Oxidative stress arising due to overproduction of reactive oxygen species, coupled with altered antioxidant capacities has been implicated in the pathogenesis of all types of cancers. However, the extent of lipid peroxidation and the status of antioxidants in canine mammary tumours have not been investigated. The present study was designed to evaluate the oxidant-antioxidant profile in canine mammary tumours. Lipid peroxidation as evidenced by the formation of thiobarbituric acid-reactive substances, lipid hydroperoxides, and conjugated dienes, as well as the status of the antioxidants superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase, glutathione S-transferase and vitamin C, in tumour tissues of 25 bitches was estimated. Lipid peroxidation in tumour tissues was enhanced compared to the corresponding adjacent uninvolved tissues. This was accompanied by significant elevation in both enzymatic and non-enzymatic antioxidants. This study suggests that upregulation of antioxidants induced by lipid peroxidation confers a selective growth advantage to tumour cells over their adjacent normal counterparts. PMID:15751580

  13. Expression and significance of CHIP in canine mammary gland tumors

    PubMed Central

    WANG, Huanan; YANG, Xu; JIN, Yipeng; PEI, Shimin; ZHANG, Di; MA, Wen; HUANG, Jian; QIU, Hengbin; ZHANG, Xinke; JIANG, Qiuyue; SUN, Weidong; ZHANG, Hong; LIN, Degui

    2015-01-01

    CHIP (Carboxy terminus of Hsc70 Interacting Protein) is an E3 ubiquitin ligase that can induce ubiquitination and degradation of several oncogenic proteins. The expression of CHIP is frequently lower in human breast cancer than in normal breast tissue. However, the expression and role of CHIP in the canine mammary gland tumor (CMGT) remain unclear. We investigated the potential correlation between CHIP expression and mammary gland tumor prognosis in female dogs. CHIP expression was measured in 54 dogs by immunohistochemistry and real-time RT-PCR. CHIP protein expression was significantly correlated with the histopathological diagnosis, outcome of disease and tumor classification. The transcriptional level of CHIP was significantly higher in normal tissues (P=0.001) and benign tumors (P=0.009) than it in malignant tumors. CHIP protein expression was significantly correlated with the transcriptional level of CHIP (P=0.0102). The log-rank test survival curves indicated that patients with low expression of CHIP had shorter overall periods of survival than those with higher CHIP protein expression (P=0.050). Our data suggest that CHIP may play an important role in the formation and development of CMGTs and serve as a valuable prognostic marker and potential target for genetic therapy. PMID:26156079

  14. Retrospective study and immunohistochemical analysis of canine mammary sarcomas

    PubMed Central

    2013-01-01

    Background Canine mammary sarcomas (CMSs) are rarely diagnosed in female dogs, which explains the scarcity of immunohistochemical findings concerning those tumors. This paper presents the results of a retrospective study into CMSs and discusses the clinical features of the analyzed tumors, the expression of intermediate filaments CK, Vim, Des and α-SMA, and the expression of p63, Ki67, ERα, PR and p53 protein. Results Four percent of all canine mammary tumors (CMTs) were classified as CMSs, and they represented 5.1% of malignant CMTs. The mean age at diagnosis was 11.1 ± 2.8 years. Large breed dogs were more frequently affected (38.7%). The majority of observed CMSs were fibrosarcomas (2.1%). All CMSs expressed vimentin, and higher levels of vimentin expression were noted in fibrosarcomas and osteosarcomas. Ki67 expression was significantly correlated with the grade of CMS. Conclusions Our results revealed that CMSs form a heterogeneous group, therefore, immunohistochemical examinations could support differential and final diagnosis. Although this study analyzed a limited number of samples, the reported results can expand our knowledge about CMSs. Further work is required in this field. PMID:24321325

  15. Expression and significance of CHIP in canine mammary gland tumors.

    PubMed

    Wang, Huanan; Yang, Xu; Jin, Yipeng; Pei, Shimin; Zhang, Di; Ma, Wen; Huang, Jian; Qiu, Hengbin; Zhang, Xinke; Jiang, Qiuyue; Sun, Weidong; Zhang, Hong; Lin, Degui

    2015-11-01

    CHIP (Carboxy terminus of Hsc70 Interacting Protein) is an E3 ubiquitin ligase that can induce ubiquitination and degradation of several oncogenic proteins. The expression of CHIP is frequently lower in human breast cancer than in normal breast tissue. However, the expression and role of CHIP in the canine mammary gland tumor (CMGT) remain unclear. We investigated the potential correlation between CHIP expression and mammary gland tumor prognosis in female dogs. CHIP expression was measured in 54 dogs by immunohistochemistry and real-time RT-PCR. CHIP protein expression was significantly correlated with the histopathological diagnosis, outcome of disease and tumor classification. The transcriptional level of CHIP was significantly higher in normal tissues (P=0.001) and benign tumors (P=0.009) than it in malignant tumors. CHIP protein expression was significantly correlated with the transcriptional level of CHIP (P=0.0102). The log-rank test survival curves indicated that patients with low expression of CHIP had shorter overall periods of survival than those with higher CHIP protein expression (P=0.050). Our data suggest that CHIP may play an important role in the formation and development of CMGTs and serve as a valuable prognostic marker and potential target for genetic therapy. PMID:26156079

  16. Cutaneous metastasis in anorectal adenocarcinoma.

    PubMed

    Varma, Krishnendra; Singh, Ujjwal Kumar; Jain, Mansi; Dhand, P L

    2015-01-01

    Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum) of a metastatic adenocarcinoma. PMID:26009722

  17. Cutaneous metastasis in anorectal adenocarcinoma

    PubMed Central

    Varma, Krishnendra; Singh, Ujjwal Kumar; Jain, Mansi; Dhand, P. L.

    2015-01-01

    Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum) of a metastatic adenocarcinoma. PMID:26009722

  18. Matrix metalloproteinases and their inhibitors in canine mammary tumors

    PubMed Central

    2011-01-01

    Background Malignant canine mammary tumors represent 50% of all neoplasms in female dogs. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be involved in tumor progression, and they are also associated with the reactive stroma, which provides structural and vascular support for tumor growth. Results MMP-2, MMP-9 and MT1-MMP were expressed at both the mRNA and protein levels in tumor samples. MMP-2 and MMP-9 immunohistochemical reactions were evident both in the epithelial tumor cells and in the stromal compartment to varying degrees; in particular, the intensity of the MMP-2 staining was stronger in the stromal fibroblasts close to epithelial tumor cells in simple carcinomas than in adenomas. These data were supported by gelatin-zymography; bands for the active form of MMP-2 were found in 94% of carcinoma samples, compared with 17% of benign tumor samples. The gene expression and immunohistochemical results for MT1-MMP were comparable to those for MMP-2. The immunoreactivity for MMP-13 and TIMP-2 was lower in carcinomas than in adenomas, confirming the mRNA data for MMP-13 and the other MMP inhibitors that were evaluated. The active form of MMP-9, but not the active form of MMP-2, was identified in the plasma of all of the tested dogs. Conclusions Our findings suggest that MMP-9, MMP-2 and MT1-MMP, which are synthesized by epithelial cancer cells and cancer-associated fibroblasts, play an important role in malignant canine mammary tumors. The reduction of MMP-13 and TIMP-2 could also be a significant step in malignant transformation. MMP-2 and MT1-MMP could be further evaluated as future biomarkers for predicting the progression and prognosis of canine mammary tumors. PMID:21726449

  19. Serum and Tissue Steroid Hormone Levels in Canine Mammary Tumours: Clinical and Prognostic Implications.

    PubMed

    Queiroga, F L; Pérez-Alenza, D; González-Gil, A; Silván, G; Peña, L; Illera, J C

    2015-10-01

    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. PMID:26332137

  20. How Is Small Intestine Adenocarcinoma Staged?

    MedlinePlus

    ... small intestine adenocarcinoma, by stage How is small intestine adenocarcinoma staged? Staging is a process that tells ... distant m etastasis (M). T categories for small intestine adenocarcinoma T categories of small intestine cancer describe ...

  1. Insulin receptors in the mammary gland

    SciTech Connect

    Smith, D.H.

    1986-01-01

    Insulin binding studies were conducted using mammary membrane preparations to further the authors understanding of insulin's role in regulating mammary metabolism, particularly ruminant mammary metabolism. Specific objectives were to: (1) characterize insulin binding to bovine mammary microsomes and determine if the specificity and kinetics of binding indicate the presence of insulin receptors in bovine mammary gland; (2) examine and compare insulin binding by liver and mammary microsomes of the pig and dairy cow; (3) examine insulin binding to bovine milk fat globule membranes (MFGM) and evaluate this model's usefulness in assessing insulin receptor regulation in the mammary gland of the cow; (4) examine the effect of dietary fat in insulin binding by rat mammary and liver microsomes. The specificity and kinetics of /sup 125/I-insulin binding of bovine mammary microsomes indicated the presence of insulin receptors in bovine mammary gland. Bovine liver and mammary microsomes specifically bound less /sup 125/I-insulin than did the corresponding porcine microsomes, and mammary microsomes, regardless of species, specifically bound less /sup 125/I-insulin than did liver microsomes. These differences in binding suggest differences in insulin responsiveness between pigs and cattle, as well as between the liver and mammary glands.

  2. Study of prostatic disease in dogs: 177 cases (1981-1986).

    PubMed

    Krawiec, D R; Heflin, D

    1992-04-15

    Historical and physical signs associated with prostatic disease diagnosed in dogs over a 5.5-year period were defined. One hundred seventy-seven male dogs were determined to have prostatic abnormality. Of the 177 dogs, 87 were determined to have specific prostatic disease. The most common prostatic disease identified in this study was bacterial prostatitis, followed by prostatic cyst, prostatic adenocarcinoma, and benign hyperplasia. The most common prostatic disease identified in neutered dogs was prostatic adenocarcinoma. Mean age at onset of prostatic disease was 8.9 years; statistically significant difference was not observed between age at onset of the various types of prostatic disease identified. Doberman Pinscher was the most common breed with prostate disease. Twenty-nine percent of dogs with a specifically identifiable prostatic disease had signs of systemic illness, 41% had signs of lower urinary tract disease, 28% had signs of gastrointestinal tract abnormalities, and 13% had signs of locomotor difficulty. PMID:1376729

  3. The Mammary Glands of Macaques

    PubMed Central

    Cline, J. Mark; Wood, Charles E.

    2009-01-01

    This review describes the normal biology and physiology of the mammary gland in macaques, including the typical histologic appearance across the life span (development, reproductive maturity, lactation, and senescence). The molecular events regulating breast morphogenesis are described, as well as systemic and local hormonal regulators of mammary gland proliferation, differentiation, and function. Similarities and differences to the human breast are described. Regulatory events are illuminated by discussion of genetically modified mouse models. Tissue response markers, including immunohistochemical markers of proliferation and other hormonally induced changes and studies to date, regarding the effects of exogenous hormones, are briefly summarized. In general, estrogens stimulate progesterone receptor expression and proliferation in the mammary gland, and combinations of estrogens and progestogens cause greater proliferation than estrogens alone. Evaluation of novel chemical agents in macaques requires careful evaluation of age and hormonal context to avoid the confounding effects of mammary gland development, past reproductive history, and other influences on mammary gland morphology. The expression of proliferation markers and progesterone receptors may be used as biomarkers to measure chemically induced hormonal effects. PMID:21475638

  4. T2* relaxation times of intraductal murine mammary cancer, invasive mammary cancer, and normal mammary gland

    PubMed Central

    Hipp, Elizabeth; Fan, Xiaobing; Jansen, Sanaz A.; Markiewicz, Erica J.; Vosicky, James; Newstead, Gillian M.; Conzen, Suzanne D.; Krausz, Thomas; Karczmar, Gregory S.

    2012-01-01

    Purpose: This study investigates the feasibility of T2* to be a diagnostic indicator of early breast cancer in a mouse model. T2* is sensitive to susceptibility effects due to local inhomogeneity of the magnetic field, e.g., caused by hemosiderin or deoxyhemoglobin. In these mouse models, unlike in patients, the characteristics of single mammary ducts containing pure intraductal cancer can be evaluated. Methods: The C3(1)SV40Tag mouse model of breast cancer (n = 11) and normal FVB/N mice (n = 6) were used to measure T2* of normal mammary gland tissue, intraepithelial neoplasia, invasive cancers, mammary lymph nodes, and muscle. MRI experiments were performed on a 9.4T animal scanner. High resolution (117 microns) axial 2D multislice gradient echo images with fat suppression were acquired first to identify inguinal mammary gland. Then a multislice multigradient echo pulse sequence with and without fat suppression were performed over the inguinal mammary gland. The modulus of a complex double exponential decay detected by the multigradient echo sequence was used to fit the absolute proton free induction decay averaged over a region of interest to determine the T2* of water and fat signals. Results: The measured T2* values of tumor and muscle are similar (∼15 ms), and almost twice that of lymph nodes (∼8 ms). There was a statistically significant difference (p < 0.03) between T2* in normal mammary tissue (13.7 ± 2.9 ms) and intraductal cancers (11 ± 2.0 ms) when a fat suppression pulse was applied. Conclusions: These are the first reported T2* measurements from single mammary ducts. The results demonstrated that T2* measurements may have utility for identifying early pre-invasive cancers in mouse models. This may inspire similar research for patients using T2* for diagnostic imaging of early breast cancer. PMID:22380363

  5. Gross and histopathologic effects of medroxyprogesterone acetate and progesterone on the mammary glands of adult beagle bitches.

    PubMed

    Concannon, P W; Spraker, T R; Casey, H W; Hansel, W

    1981-09-01

    Adult beagle bitches received 0.2 to 75 mg/kg doses of medroxyprogesterone acetate (MPA) once every 3 months for 1 to 1.5 years. Doses greater than 2.0 mg/kg prevented the recurrence of ovarian cycles; lower doses did not. MPA (10 and 75 mg/kg) induced a dose-related development of multiple, large (greater than 5 mm diameter) mammary nodules that occurred earlier in older dogs than in younger dogs. MPA-induced mammary hyperplasia and nonnodular dysplasias were also noted. Most of the large (5 to 110 mm in diameter) MPA-induced nodules were, in nearly equal numbers, nodules of lobular hyperplasia, simple adenomas, or complex adenomas. Such benign mammopathies all appear to have histopathologic counterparts in human breast disease. However, simple adenomas are uncommon in both humans and dogs. Some of the MPA-induced nodules were benign mixed tumors with cartilaginous metaplasia. No malignant tumors were found. Induction of mammary tumors by 75 mg MPA/kg was not affected by prior ovariectomy but was reached by prior hypophysectomy, suggesting involvement of pituitary secretion in MPA-induced mammary gland disease. PMID:6456940

  6. Dog bites.

    PubMed

    1991-04-01

    Although our canine companions can provide us with many hours of unyielding love and faithfulness, it is important to remember that these same loving creatures inflict 500,000 to one million bites per year, accounting for one percent of all emergency room visits nationwide. Ten percent of these injuries require suturing, one to two percent require hospitalization, and approximately one-third of dog bite injuries cause lost time from work or school. The United States Postal Service spends more than $250,000 annually just for prevention and treatment of dog bite injuries involving letter carriers! Still think that adorable pooch is harmless? Read on. PMID:1857330

  7. Incidence of mammary tumors in the canine population living in the Veneto region (Northeastern Italy): Risk factors and similarities to human breast cancer.

    PubMed

    Vascellari, Marta; Capello, Katia; Carminato, Antonio; Zanardello, Claudia; Baioni, Elisa; Mutinelli, Franco

    2016-04-01

    Although mammary gland tumors (MT) are the most-common type of tumor in intact female dogs, there is little information about their incidence in dog population. Data on MT in female dogs was retrieved from the Animal Tumor registry of dogs and cats of Venice and Vicenza provinces during 2005-2013 and was analyzed to visualize crude incidence rates by breed and across age categories. Overall, 2744 mammary tumors were reported accounting for 54% of all tumors in female dogs. The annual incidence rate (IR) was 250 cases per 100,000 dogs. The most frequent malignant tumors were complex carcinomas, consisting of both epithelial and myoepithelial tissues (IR=71.89), and simple carcinomas (IR=62.59). The MT incidence rate increased through the study period; particularly in the last 4 years, and malignant neoplasms occurred more frequently (70%) than the benign counterparts (30%). Seventy-four percent of tumors were diagnosed in intact females, and the mean age at diagnosis was significantly higher for spayed dogs than for intact ones. MT were less frequent in dogs younger than 6 years and increased up to approximately 60% for ages between 8 and 13 years. The purebred dogs had a higher probability to have a malignant neoplasm than mixed-breed dogs, particularly in dogs younger than 7 years, and the Samoyed, Dobermann, Schnauzer and Yorkshire Terrier breeds were more inclined to develop malignant MT. The incidence of MT in dogs is increasing, and IRs are comparable to that in women. The epidemiological similarities between dogs and women support the validity of canine MT as a model for human breast cancer. PMID:26948297

  8. Pancreatic adenocarcinoma: Outstanding problems

    PubMed Central

    Zakharova, Olga P; Karmazanovsky, Grigory G; Egorov, Viacheslav I

    2012-01-01

    Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%. Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma. About 40% of patients have locally advanced nonresectable disease. In the past, determination of pancreatic cancer resectability was made at surgical exploration. The development of modern imaging techniques has allowed preoperative staging of patients. Institutions disagree about the criteria used to classify patients. Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition of borderline resectable pancreatic cancer is also lacking. Thus, there is much room for improvement in all aspects of treatment for pancreatic cancer. Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer. With improved surgical techniques and advanced perioperative management, vascular resection and reconstruction are performed more frequently; patients thought once to be unresectable are undergoing radical surgery. However, when attempting heroic surgery, a realistic approach concerning the patient’s age and health status, probability of recovery after surgery, perioperative morbidity and mortality and life quality after tumor resection is necessary. PMID:22655124

  9. Adenoma-Like Adenocarcinoma

    PubMed Central

    Gonzalez, Raul S.; Cates, Justin M.M.; Washington, M. Kay; Beauchamp, R. Daniel; Coffey, Robert J.; Shi, Chanjuan

    2015-01-01

    Aims A subset of colorectal carcinomas (CRCs) architecturally and cytologically resembles adenomatous change, making them difficult to diagnose on biopsy. This subset has not been well-characterized to date. Methods and results For 35 carcinomas with adenomatous-like areas (cytologic and surface architectural appearance that would be insufficient to warrant a diagnosis of adenocarcinoma if evaluated on biopsy), we recorded staging information, molecular data, clinical outcome, whether precursor adenoma was present, and whether prior biopsy had been diagnosed as malignant. Despite advanced T-category in 23 (66%) tumors, only 7 (20%) had nodal metastases, and only 5 patients (15%) developed distant metastases. Fifteen cases (43%) had been diagnosed as adenoma on biopsy. Twenty-one resections (60%) showed no residual associated adenoma, including 9 called adenoma on biopsy. Median follow-up was 44 months. Four patients (12%) died of disease; 22 were alive at last follow-up. KRAS mutation was seen in 14/24 (58%), and 4/17 (24%) were microsatellite-unstable. Patients had significantly improved survival compared to a cohort of patients with conventional well-differentiated CRC after controlling for age and stage (p=0.011). Conclusions Adenoma-like adenocarcinoma is an uncommon variant of CRC with a low rate of metastasis and good prognosis. Biopsy diagnosis of this lesion may be challenging. PMID:25913616

  10. Cellular Foundations of Mammary Tubulogenesis

    PubMed Central

    Huebner, Robert J.; Ewald, Andrew J.

    2014-01-01

    The mammary gland is composed of a highly branched network of epithelial tubes, embedded within a complex stroma. The mammary epithelium originates during embryonic development from an epidermal placode. However, the majority of ductal elongation and bifurcation occurs postnatally, in response to steroid hormone and growth factor receptor signaling. The process of pubertal branching morphogenesis involves both elongation of the primary ducts across the length of the fat pad and a wave of secondary branching that elaborates the ductal network. Recent studies have revealed that mammary epithelial morphogenesis is accomplished by transitions between simple and stratified organization. During active morphogenesis, the epithelium is stratified, highly proliferative, has few intercellular junctions, and exhibits incomplete apico-basal polarity. In this review, we discuss recent advances in our understanding of the relationship between epithelial architecture, epithelial polarity, and ductal elongation. PMID:24747369

  11. Effects of 900 MHz GSM wireless communication signals on DMBA-induced mammary tumors in rats.

    PubMed

    Yu, Da; Shen, Yonghao; Kuster, Niels; Fu, Yiti; Chiang, Huai

    2006-02-01

    The purpose of the study was to investigate whether exposure to 900 MHz GSM wireless communication signals enhances mammary tumor development and growth induced by low-dose DMBA. Five hundred female Sprague-Dawley rats were treated with a single dose of 35 mg/kg DMBA and then divided into five groups in a blinded fashion: one cage control group and four exposure groups, including three microwave exposure groups and one sham exposure with specific absorption rates (SARs) of 4.0, 1.33, 0.44 and 0 W/kg, respectively. Exposure started on the day after DMBA administration and lasted 4 h/day, 5 days/week for 26 weeks. Rats were weighed and palpated weekly for the presence of tumors and were killed humanely at the end of the 26-week exposure period. All mammary glands were examined histologically. There were no statistically significant differences in body weight between sham- and GSM microwave-exposed groups. No significant differences in overall mammary tumor incidence, latency to tumor onset, tumor multiplicity, or tumor size were observed between microwave- and sham-exposed groups. There was a tendency for reduction of mammary adenocarcinoma incidence in the lowest microwave exposure group (0.44 W/ kg) compared with the sham-exposed group (P = 0.058). Additionally, a higher incidence of adenocarcinoma was noticed in the 4.0 W/kg group from the 15th to 26th weeks, especially in the 19th week (P = 0.358 compared to sham). However, neither tendency was statistically significant; thus this study does not provide evidence that GSM microwave exposure promotes mammary tumor development in rats. In the present study there were significant differences between the cage controls and the experimental groups (sham and exposure). Body weight and mammary tumor (malignant plus benign) incidence in the cage control group were significantly higher than in the sham- and GSM microwave-exposed groups. The latency to the mammary tumor onset was significantly shorter in the cage control

  12. Dog Fights

    ERIC Educational Resources Information Center

    Taylor, Kelley R.

    2010-01-01

    Bringing service animals into schools raises serious questions about how to meet one student's special needs while ensuring the educational well-being of all. This article discusses how schools grapple with the practical and legal questions involved in allowing service dogs on campus. The author cites a case in 2009 called "Kalbfleisch v. Columbia…

  13. Radiographic and ultrasonographic findings of uterine neoplasms in nine dogs.

    PubMed

    Patsikas, Michail; Papazoglou, Lysimachos G; Jakovljevic, Samuel; Papaioannou, Nikolaos G; Papadopoulou, Paraskevi L; Soultani, Christina B; Chryssogonidis, Ioannis A; Kouskouras, Konstantinos A; Tziris, Nikolaos E; Charitanti, Afroditi A

    2014-01-01

    The records of nine female intact dogs with histologically confirmed uterine tumors were reviewed retrospectively, and the related radiographic and ultrasonographic signs of the lesions detected were recorded. Radiography revealed a soft-tissue opacity between the urinary bladder and colon in six of seven dogs with uterine body and/or cervical tumors, and a soft-tissue opacity in the midventral abdomen in two dogs with uterine horn tumors. Ultrasonography revealed masses in all dogs with uterine body/cervical tumors and could delineate the origin of the mass in one of two dogs with uterine horn tumors. The mass was characterized ultrasonographically as solid in three dogs (all leiomyomas), solid with cystic component in four dogs (two adenocarcinomas, one leiomyoma, and one fibroleiomyoma), and cystic in two (both leiomyomas). Hyperechoic foci in the mass were observed in three dogs. Ultrasonography was a useful method for demonstrating uterine body and/or cervical tumors. However, it was not possible to ascertain sonographically that a mass originated in a uterine horn unless there was associated evidence of uterine horn to which the mass could be traced. The ultrasonographic appearance of uterine tumors was variable, and the type of neoplasm could only be determined by taking biopsies of the mass. PMID:25028432

  14. Neoadjuvant therapy for gastroesophageal adenocarcinoma

    PubMed Central

    Samalin, Emmanuelle; Ychou, Marc

    2016-01-01

    Gastric and esophageal adenocarcinomas are one of the main causes of cancer-related death worldwide. While the incidence of gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction adenocarcinoma is rising rapidly in Western countries. Considering that surgical resection is currently the major curative treatment, and that the 5-year survival rate highly depends on the pTNM stage at diagnosis, gastroesophageal adenocarcinoma management is very challenging for oncologists. Several treatment strategies are being evaluated, and among them systemic chemotherapy, to decrease recurrences and improve overall survival. The MAGIC and FNCLCC-FFCD trials showed a survival benefit of perioperative chemotherapy in patients with operable gastric and lower esophageal cancer, and these results had an impact on the European clinical practice. New strategies, including induction chemotherapy followed by preoperative chemoradiotherapy, targeted therapies in combination with perioperative chemotherapy and the new cytotoxic regimens, are currently assessed to improve current standards and help developing patient-tailored therapeutic interventions. PMID:27298768

  15. Neoadjuvant therapy for gastroesophageal adenocarcinoma.

    PubMed

    Samalin, Emmanuelle; Ychou, Marc

    2016-06-10

    Gastric and esophageal adenocarcinomas are one of the main causes of cancer-related death worldwide. While the incidence of gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction adenocarcinoma is rising rapidly in Western countries. Considering that surgical resection is currently the major curative treatment, and that the 5-year survival rate highly depends on the pTNM stage at diagnosis, gastroesophageal adenocarcinoma management is very challenging for oncologists. Several treatment strategies are being evaluated, and among them systemic chemotherapy, to decrease recurrences and improve overall survival. The MAGIC and FNCLCC-FFCD trials showed a survival benefit of perioperative chemotherapy in patients with operable gastric and lower esophageal cancer, and these results had an impact on the European clinical practice. New strategies, including induction chemotherapy followed by preoperative chemoradiotherapy, targeted therapies in combination with perioperative chemotherapy and the new cytotoxic regimens, are currently assessed to improve current standards and help developing patient-tailored therapeutic interventions. PMID:27298768

  16. Adenocarcinoma of the cervical stump

    SciTech Connect

    Goodman, H.M.; Niloff, J.M.; Buttlar, C.A.; Welch, W.R.; Marck, A.; Feuer, E.J.; Lahman, E.A.; Jenison, E.; Knapp, R.C. )

    1989-11-01

    Sixteen women with adenocarcinoma of the cervical stump were treated over a 15-year period. The median survivals of 40 months for stage IB and 17 months for stages II and III were significantly worse compared with those for patients treated for cervical adenocarcinoma of the intact uterus or squamous carcinoma of the cervical stump. The poor results were due to both local and distant failure. Implications regarding tumor radiosensitivity and adjuvant therapy in these high-risk patients are discussed.

  17. Prognostic significance of tissue and serum HER2 and MUC1 in canine mammary cancer.

    PubMed

    Campos, Liliane C; Silva, Juliana O; Santos, Fabiana S; Araújo, Marina R; Lavalle, Gleidice E; Ferreira, Enio; Cassali, Geovanni D

    2015-07-01

    The aim of our study was to compare serum levels and protein tissue of human epidermal growth factor receptor-2 proto-oncogene (HER2) and mucin 1 (MUC1) using an antigen-capture enzyme-linked immunosorbent assay and immunohistochemistry (IHC) in canine mammary carcinomas and investigate how the 2 markers correlate with dogs with metastasis and without metastasis to a regional lymph node. Forty-eight female dogs were selected, including 14 with non-metastatic cancer, 14 with lymph node metastasis, and 20 healthy animals. Serum samples were collected from all the animals and tissues from 28 dogs with malignant mammary tumor with or without metastasis for evaluated HER2 and MUC1 expression. Tissue sample were evaluated for MUC1 and HER2 immunoexpression by IHC. The results showed measurable serum levels of MUC1 and HER2 in all groups. While serum MUC1 levels were significantly higher in animals with metastasis than the other 2 groups, no increase was observed in HER2 serum levels. The MUC1 IHC results showed that only membrane immunostaining was significantly different between the groups. Statistically, there was an association between immunostaining and the serum HER2 levels. Our results indicate that serum concentrations of HER2 and the IHC staining pattern for HER2 in primary tumor do not correlate with the presence of regional metastasis. However, increased concentrations of MUC1 in the serum of dogs with mammary cancer are associated with the presence of metastasis to regional lymph nodes. A membrane pattern of IHC staining for MUC1 in the primary tumor suggests that metastases to regional lymph node are present. PMID:26179096

  18. Ligand-Independent Canonical Wnt Activity in Canine Mammary Tumor Cell Lines Associated with Aberrant LEF1 Expression

    PubMed Central

    van Wolferen, Monique E.; Rao, Nagesha A. S.; Grizelj, Juraj; Vince, Silvijo; Hellmen, Eva; Mol, Jan A.

    2014-01-01

    Pet dogs very frequently develop spontaneous mammary tumors and have been suggested as a good model organism for breast cancer research. In order to obtain an insight into underlying signaling mechanisms during canine mammary tumorigenesis, in this study we assessed the incidence and the mechanism of canonical Wnt activation in a panel of 12 canine mammary tumor cell lines. We show that a subset of canine mammary cell lines exhibit a moderate canonical Wnt activity that is dependent on Wnt ligands, similar to what has been described in human breast cancer cell lines. In addition, three of the tested canine mammary cell lines have a high canonical Wnt activity that is not responsive to inhibitors of Wnt ligand secretion. Tumor cell lines with highly active canonical Wnt signaling often carry mutations in key members of the Wnt signaling cascade. These cell lines, however, carry no mutations in the coding regions of intracellular Wnt pathway components (APC, β-catenin, GSK3β, CK1α and Axin1) and have a functional β-catenin destruction complex. Interestingly, however, the cell lines with high canonical Wnt activity specifically overexpress LEF1 mRNA and the knock-down of LEF1 significantly inhibits TCF-reporter activity. In addition, LEF1 is overexpressed in a subset of canine mammary carcinomas, implicating LEF1 in ligand-independent activation of canonical Wnt signaling in canine mammary tumors. We conclude that canonical Wnt activation may be a frequent event in canine mammary tumors both through Wnt ligand-dependent and novel ligand–independent mechanisms. PMID:24887235

  19. [A case of Peutz-Jeghers syndrome combined with bilateral breast cancer, an adenocarcinoma of the cervix and ovarian genital cord neoplasms with annular tubules].

    PubMed

    Gloor, E

    1978-05-13

    The clinico-pathological findings are presented in a case of Peutz-Jeghers syndrome associated with a bilateral mammary invasive ductal carcinoma, a well-differentiated mucinous adenocarcinoma of the cervix and microscopic, bilateral ovarian sex cord tumors with annular tubules. The sex cord tumor with annular tubules was described in 1970 by SCULLY, who recognized its striking association with the Peutz-Jeghers syndrome. Two cases of adenocarcinoma of the cervix and another case of uterine adenocarcinoma of unspecified localization associated with Peutz-Jeghers syndrome were found in the literature. It is possible that women with Peutz-Jeghers syndrome run an increased risk of developing adenocarcinoma of the uterine cervix. PMID:644282

  20. Evaluation of melatonin treatment in primary culture of canine mammary tumors.

    PubMed

    Lopes, Juliana Ramos; Maschio, Larissa Bazela; Jardim-Perassi, Bruna Victorasso; Moschetta, Marina Gobbe; Ferreira, Lívia Carvalho; Martins, Gustavo Rodrigues; Gelaleti, Gabriela Bottaro; De Campos Zuccari, Debora Aparecida Pires

    2015-01-01

    Mammary neoplasias are the most common tumors observed in female dogs. Identification of these tumors is valuable in order to identify beneficial therapeutic agents as alternative treatments for this tumor type. Oral administration of melatonin appears to exert an oncostatic effect on mammary neoplasia and may have a possible mechanism of action through its interaction with estrogen receptors on epithelial cells. Hence, we analyzed the potential therapeutic value of melatonin in tumors that are estrogen-dependent or -independent, and established a relationship of its action with the expression of the melatonin receptors MT1 and MT2. Furthermore, we analyzed the rate of cell proliferation and apoptosis after treatment with melatonin. Cell cultures were performed using 10 canine mammary tumor fragments and were divided into estrogen receptor (ER)-positive and ER-negative tumors. The results showed that both ER-positive and ER-negative tumors had decreased cell viability and proliferation after treatment with melatonin (p<0.05), although treatment was more effective in the ER-positive tumors. Analysis of the relative expression of the MT1 and MT2 genes by quantitative PCR was performed and the data were compared with the expression of ER in 24 canine mammary tumors and the cellular response to melatonin in 10 samples. MT1 was overexpressed in ER-positive tumors (p<0.05), whereas MT2 was not expressed. Furthermore, melatonin treatment in ER-positive tumors showed an efficient oncostatic effect by inhibiting cell viability and proliferation and inducing apoptosis. These results suggest that melatonin decreased neoplastic mammary cell proliferation and viability and induced apoptosis, with greater efficacy in ER-positive tumors that have a high expression of melatonin receptor MT1. This is a strong evidence for the use of melatonin as a therapeutic agent for estrogen-dependent canine mammary tumors. PMID:25384569

  1. Angiotropic metastatic malignant melanoma in a canine mammary gland

    PubMed Central

    Yang, Hai Jie; Lee, Eun-Mi; Kim, Ah-Young; Lee, Eun-Joo; Hong, IL-Hwa; Huh, Sung-Oh

    2011-01-01

    An eleven-year-old spayed female Yorkshire Terrier presented with a sublumbar mass and upon ultrasonographic examination, was revealed to have a mammary gland tumor. Black to reddish colored masses, located in the visceral peritoneum of the sublumbar region was observed on laparotomy with masectomy of the right side. In the laparotomy, we observed reddish masses multifocally located in the serosal membrane of the large intestine. Histopathologic examination of the intestinal and abdominal mass showed highly invasiveness into the muscle and metastasis of melanocytic tumor cells through the blood vessels. The mammary glands showed abnormal hyperplasia of melanocytes, destruction of the normal glands by tumor cells and infiltration of some lymphocytes in the pool of melanocytic cells. We have identified a malignant melanoma containing an angiotumoral complex in which tumor cells occupied a pericytic location along the microvessels with intravasation determined by immunohistochemistry for S100 protein and protein kinase C-α. Histologic findings in this dog lead to a diagnosis of an angiotropic metastatic malignant melanoma. PMID:22232646

  2. Temperature-dependent elaboration of collagenase by the renal adenocarcinoma of the leopard frog, Rana pipiens.

    PubMed

    Ogilvie, D J; McKinnell, R G; Tarin, D

    1984-08-01

    Naturally occurring renal adenocarcinoma in North American leopard frogs, Rana pipiens, metastasize frequently (77%) when these ectothermic animals are kept in a warm environment but not when they are kept cold. We have found that explants of these tumors secrete collagenase, an enzyme capable of dissolving connective tissue fibers and found previously to be closely correlated with metastatic colony-forming capability of murine mammary tumors, and that the amount released sequentially rises and falls as the ambient temperature is shifted between metastasis-permissive and -inhibitory levels. In contrast, normal frog renal tissue has low collagenase output, unaffected by temperature changes. PMID:6331646

  3. Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

    PubMed Central

    2010-01-01

    Background Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs

  4. Value of Mammary Thermography in Differential Diagnosis

    PubMed Central

    Nathan, B. E.; Burn, J. Ian; MacErlean, D. P.

    1972-01-01

    Thermographic examinations of the breasts were carried out in 359 women, most of whom had mammary symptoms. Of the 195 patients with abnormal thermograms, 27 had cancer of the breast, 53 had benign lesions, and 115 had no confirmed organic disease. The incidence of false-positive thermograms was 59%. Of the 164 patients with normal thermograms, 116 had no confirmed organic disease, 41 had benign lesions, and 7 had cancer. The incidence of false-negative mammary thermograms was 29%. We conclude that mammary thermography is of no practical value in the differential diagnosis of symptomatic mammary disease. PMID:5022040

  5. Glucose transporter expression in rat mammary gland.

    PubMed Central

    Burnol, A F; Leturque, A; Loizeau, M; Postic, C; Girard, J

    1990-01-01

    The expression of different glucose transporter isoforms was measured during the development and differentiation of the rat mammary gland. Before conception, when the mammary gland is mainly composed of adipocytes, Glut 4 and Glut 1 mRNAs and proteins were present. During pregnancy, the expression of Glut 4 decreased progressively, whereas that of Glut 1 increased. In the lactating mammary gland only Glut 1 was present, and was expressed at a high level. The absence of Glut 4 suggests that glucose transport is not regulated by insulin in the lactating rat mammary gland. Images Fig. 1. Fig. 2. PMID:2396989

  6. Cat and Dog Bites

    MedlinePlus

    MENU Return to Web version Cat and Dog Bites Cat and Dog Bites How should I take care of a bite from a cat or a dog? Whether from a family pet or a neighborhood stray, cat and dog bites are common. Here are some ...

  7. Flor-Essence? Herbal Tonic Promotes Mammary Tumor Development in Sprague Dawley Rats

    SciTech Connect

    Bennett, L; Montgomery, J; Steinberg, S; Kulp, K

    2004-01-28

    Background: Women who are diagnosed with breast cancer often self-administer complementary and alternative medicines to augment their conventional treatments, improve health, or prevent recurrence. Flor-Essence{reg_sign} Tonic is a complex mixture of herbal extracts used by cancer patients because of anecdotal evidence that it can treat or prevent disease. Methods: Female Sprague Dawley rats were given water or exposed to 3% or 6% Flor-Essence{reg_sign} beginning at one day of age. Mammary tumors were induced with a single oral 40 mg/kg/bw dose of dimethylbenz(a)anthracene at 50 days of age and sacrificed at 23 weeks. Rats were maintained on AIN-76A diet. Results: Control rats had palpable mammary tumor incidence of 51.0% at 19 weeks of age compared to 65.0% and 59.4% for the 3% and 6% Flor-Essence{reg_sign} groups respectively. Overall, no significant difference in time until first palpable tumor was detected among any of the groups. At necropsy, mammary tumor incidence was 82.5% for controls compared to 90.0% and 97.3% for rats consuming 3% and 6% Flor-Essence{reg_sign}, respectively. Mean mammary tumor multiplicity ({+-}SES) for the controls was 2.8 ({+-} 0.5) and statistically different from the 3% or 6% Flor- Essence{reg_sign} groups with 5.2 ({+-} 0.7), and 4.8 ({+-} 0.6), respectively (p{<=}0.01). As expected, the majority of isolated tumors were diagnosed as adenocarcinomas. Conclusions: Flor-Essence{reg_sign} can promote mammary tumor development in the Sprague Dawley rat model. This observation is contrary to widely available anecdotal evidence as well as the desire of the consumer that this commercially available herbal tonic will suppress and/or inhibit tumor growth.

  8. Mammary neoplasms of the bitch.

    PubMed

    Cotchin, E

    1958-01-01

    In this paper, the interrelationships of the neoplasms of the canine mammary gland are investigated. These neoplasms are a group of tumors of a great variety of histological structure and sometimes of uncertain histogenesis. Particular attention is given to the histogenesis of the mucoid, cartilaginous, and bony elements. From 1950-56, a macroscopic and histological examination of mammary neoplasms from 424 bitches (2-17 years of age) was made. The tumors from 381 bitches were removed surgically while the others came from 43 bitches who were examined postmortem. Of the 160 tumors whose location was recorded, 105 occurred in the 2 hinder glands, 19 in the middle glands, and 46 in one or another of the 2 anterior glands. 186 of the 424 bitches bore malignant mammary tumors (87 carcinomas, 73 sarcomas, 27 complex malignant tumors) and 249 had benign tumors (19 simple and 230 complex). 40 of the benign complex tumors contained bone, an additional 63 contained cartilage but no bone, and 67 showed mucoid tissue but no cartilage or bone. It is suggested that there is a predominant proliferation of myoepithelial cells which tend to become embedded in a mucoid or chondroid matrix. The bone in the tumors appears to be formed by endochondral ossification of preformed cartilage, or by intramembranous ossification in the connective tissue of the tumor. Metastases were present in 41 of the 424 bitches. PMID:12311486

  9. Differentiating bronchioloalveolar carcinoma from adenocarcinoma.

    PubMed

    Schraufnagel, D; Peloquin, A; Paré, J A; Wang, N S

    1982-01-01

    The recognition of bronchioloalveolar carcinoma (BAC) as distinct from adenocarcinoma of the lung, is controversial. Using strict pathologic criteria, 43 consecutive patients with BAC were matched by year of diagnosis and compared with a similar number of patients with adenocarcinoma, and for contrast, with those with squamous and oat cell carcinoma of the lung. We demonstrated that BAC is not sex related, and is not as smoking related as the other neoplasms. Unlike epidermoid carcinoma, BAC does not show a predilection for those occupations requiring manual labor. Also, BAC is frequently distinguishable radiologically from the other three by being smaller and peripheral. A pleural tag and an air bronchogram in a mass are rather specific, and BAC is less likely to have large airway involvement and adenopathy. The percentage of patients who were free of tumor after 2 yr was greater in the BAC group than in the others, but the overall survival rate between the BAC group and the adenocarcinoma group was not. Based on inter-observer variability, there is some overlap pathologically between these 2 groups. However, when the overlap between the adenocarcinoma and the BAC groups is compared with that between the adenocarcinoma and the squamous cell carcinoma groups, the difference is not significant. We conclude that BAC should be considered a distinct clinical entity. PMID:6278997

  10. Primary adenocarcinoma of cervical esophagus.

    PubMed

    Alrawi, S J; Winston, J; Tan, D; Gibbs, J; Loree, T R; Hicks, W; Rigual, N; Lorè, J M

    2005-06-01

    Most upper esophageal malignancies are squamous cell carcinomas, rarely adenocarcinomas arising from Barrett's esophagus and very rarely adenocarcinomas from heterotopic gastric mucosa without evidence of Barrett's especially in the cervical part of the esophagus. We report a case of adenocarcinoma of the polypoid type in the upper esophagus (cervical esophagus) arising from ectopic gastric mucosa, in a 60 year-old man who presented with progressive dysphagia. Accurate diagnosis by esophagogram revealed a large mass in the cervical esophagus; CAT scan showed intraluminal mass at the level of thoracic inlet, esophagogastroscopy showed a fleshy polyp (3.2cm x 3.0cm) at 20 cm from the incisors with a biopsy confirming moderately differentiated adenocarcinoma with no evidence of Barrett's esophagus. Through a left cervical approach and resection of medial third of clavicle, the tumor was removed by partial esophagectomy followed by lymph node dissection, and proved to be T1NOMO, stage I (AJCC staging 6th ed.). Post operatively, the patient received chemoradiation with no evidence of recurrence or metastasis in six years of follow up. It seems this tumor has a much better prognosis than adenocarcinomas arising from Barrett's. To our knowledge only 19 cases have been reported in literature so far. PMID:16110768

  11. Chemoprevention of heterocyclic amine-induced mammary carcinogenesis in rats.

    PubMed

    Hirose, Masao; Nishikawa, Akiyoshi; Shibutani, Makoto; Imai, Toshio; Shirai, Tomoyuki

    2002-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most prevalent carcinogenic heterocyclic amines in the environment, targeting the colon, prostate, pancreas, and mammary gland in rodents. Chemopreventive effects of synthetic and naturally occurring compounds on PhIP-induced rat mammary carcinogenesis were investigated in a series of experiments. In a PhIP feeding model, groups of 20-21 female F344 rats each, were treated with 0.02% PhIP alone or PhIP plus 0.5% 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), 1% green tea catechins, 1% alpha-tocopherol, 0.1% ellagic acid, or 1% chlorophyllin, each in the diet, or 0.1% caffeine in drinking water for 52 weeks. To assess the mechanism of HTHQ and caffeine inhibition of PhIP-induced carcinogenesis, effects of these compound on the in vitro metabolic activation of PhIP were examined in the presence of S9 mix. In the next series of experiments, the PhIP intragastric dose model was applied to allow separate investigation of the effects of chemicals during the initiation and postinitiation periods. In these experiments, female Sprague-Dawley rats were given eight intragastric doses of 100 mg/kg body weight during the first 4-8 weeks for initiation. Either during initiation or after initiation, or only after initiation, animals were treated with either corn or perilla oil at doses of 5 and 20%, conjugated fatty acid derived from safflower oil (CFA-S) or perilla oil (CFA-P) at a dose of 1%, arctiin at doses of 0.02 and 0.2% in the diet, or sodium nitrite (NaNO(2)) at a dose of 0.2% in drinking water. In the PhIP feeding model, administration of PhIP alone for 52 weeks induced adenocarcinomas in 40% of rats, but the incidence was remarkably reduced to 5% by the simultaneous treatment with 0.5% HTHQ, a strong lipophilic phenolic antioxidant, or to 10% by 0.1% caffeine. Administration of 1% chlorophyllin exerted similar, albeit weaker, effects. alpha-Tocopherol at a dose of 0.5% only reduced the multiplicity of

  12. Evaluation of immunohistochemical markers of lymphatic and blood vessels in canine mammary tumours.

    PubMed

    Sleeckx, N; Van Brantegem, L; Fransen, E; Van den Eynden, G; Casteleyn, C; Veldhuis Kroeze, E; Van Ginneken, C

    2013-05-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Bitches with spontaneously arising CMTs represent a promising animal model for human breast cancer research. The aim of the present study was to develop an immunohistochemical protocol for the identification of blood and lymphatic vessels in CMTs. Antibodies specific for human lymphatic vessels (prox-1, lyve-1, podoplanin and D2-40) and blood vessels (von Willebrand factor [vWf], CD31 and CD34) were utilized. Serial sections of 18 samples (eight samples of normal canine mammary tissue, five benign and five malignant CMTs) were examined. Antibodies specific for podoplanin, D2-40 and CD34 showed no immunoreactivity with canine tissue. Prox-1 and CD31 were determined to be the most suitable markers for lymphatic and blood vessels, respectively. PMID:23123127

  13. Evo-devo of the mammary gland.

    PubMed

    Oftedal, Olav T; Dhouailly, Danielle

    2013-06-01

    We propose a new scenario for mammary evolution based on comparative review of early mammary development among mammals. Mammary development proceeds through homologous phases across taxa, but evolutionary modifications in early development produce different final morphologies. In monotremes, the mammary placode spreads out to form a plate-like mammary bulb from which more than 100 primary sprouts descend into mesenchyme. At their distal ends, secondary sprouts develop, including pilosebaceous anlagen, resulting in a mature structure in which mammary lobules and sebaceous glands empty into the infundibula of hair follicles; these structural triads (mammolobular-pilo-sebaceous units or MPSUs) represent an ancestral condition. In marsupials a flask-like mammary bulb elongates as a sprout, but then hollows out; its secondary sprouts include hair and sebaceous anlagen (MPSUs), but the hairs are shed during nipple formation. In some eutherians (cat, horse, human) MPSUs form at the distal ends of primary sprouts; pilosebaceous components either regress or develop into mature structures. We propose that a preexisting structural triad (the apocrine-pilo-sebaceous unit) was incorporated into the evolving mammary structure, and coupled to additional developmental processes that form the mammary line, placode, bulb and primary sprout. In this scenario only mammary ductal trees and secretory tissue derive from ancestral apocrine-like glands. The mammary gland appears to have coopted signaling pathways and genes for secretory products from even earlier integumentary structures, such as odontode (tooth-like) or odontode-derived structures. We speculate that modifications in signal use (such as PTHrP and BMP4) may contribute to taxonomic differences in MPSU development. PMID:23681303

  14. Evaluation of molecular markers in canine mammary tumors: correlation with histological grading.

    PubMed

    Vinothini, G; Balachandran, C; Nagini, S

    2009-01-01

    The objective of this study was to evaluate molecular markers involved in mammary tumorigenesis in a canine model that mimics many essential elements of human breast cancer. Thirty mammary gland tumors and control tissues obtained from female dogs were included in the study. We analyzed changes in the expression of markers of hormone and receptor status (estradiol, estrogen receptor; ER and HER-2/neu), hormone metabolism (CYP1A1 and CYP1B1), cell proliferation and survival [proliferating cell nuclear antigen (PCNA), glutathione S-transferase-P (GST-P), nuclear factor-kappaB (NF-kappaB-p50, NF-kappaB-p65), phosphorylated-inhibitor of kappaB-alpha (p-IkappaB-alpha) and IkappaB], apoptosis (Bcl-2, Bax, caspases, Apaf-1, cytochrome-C, and PARP), invasion [matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and reversion-inducing cysteine-rich protein with Kazal motifs (RECK)], angiogenesis [vascular endothelial growth factor (VEGF)], and epigenetics [DNA methyltransferase (Dnmt-1), histone deacetylase (HDAC-1)] by immunohistochemical localization and Western blot analysis and correlated these with histological grade. The present study provides evidence that increased expression of ER, HER-2/neu, estradiol, and its metabolizing enzymes, as well as proteins involved in cell proliferation, apoptosis evasion, invasion, and angiogenesis may confer a selective growth advantage to canine mammary tumors. To our knowledge this is the first report on the hallmark capabilities of canine mammary tumors, which lends credence to the view that the dog is a valuable model for human breast cancer studies. PMID:20225757

  15. Perinatally Administered Bisphenol A as a Potential Mammary Gland Carcinogen in Rats

    PubMed Central

    Acevedo, Nicole; Davis, Barbara; Schaeberle, Cheryl M.; Sonnenschein, Carlos

    2013-01-01

    Background: Environmental exposure to bisphenol A (BPA) affects mammary gland development in rodents and primates. Prenatal exposure to environmentally relevant doses of BPA increased the number of intraductal hyperplasias and ductal carcinomas in situ by 50 days of age in Wistar-Furth rats. Objective: We aimed to determine whether BPA exposure of dams during gestation only or throughout lactation affects the incidence of mammary gland neoplasia in female offspring. Methods: We treated pregnant Sprague-Dawley rats with BPA at 0, 0.25, 2.5, 25, or 250 μg BPA/kg BW/day from gestational day (GD) 9 to birth and from GD9 to postnatal day (PND) 21. Mammary glands from BPA-exposed offspring were examined at four time points for preneoplastic and neoplastic lesions. To assess circulating BPA levels, we exposed pregnant rats to vehicle or 250 μg BPA/kg BW/day during gestation only or during gestation/lactation and analyzed sera from dams, fetuses, and nursing pups for total and unconjugated BPA. Results: Total and unconjugated BPA were detected in sera from 100% of dams and fetuses and 33% of pups exposed to 250 μg BPA/kg BW/day. Unconjugated BPA levels in exposed dams and fetuses (gestational) and in exposed dams and pups (gestational/lactational) were within levels found in humans. Preneoplastic lesions developed in BPA-exposed female offspring across all doses as early as PND50. Unexpectedly, mammary gland adenocarcinomas developed in BPA-exposed offspring by PND90. Conclusions: Our findings suggest that developmental exposure to environmentally relevant levels of BPA during gestation and lactation induces mammary gland neoplasms in the absence of any additional carcinogenic treatment. Thus, BPA may act as a complete mammary gland carcinogen. Citation: Acevedo N, Davis B, Schaeberle CM, Sonnenschein C, Soto AM. 2013. Perinatally administered bisphenol A acts as a mammary gland carcinogen in rats. Environ Health Perspect 121:1040–1046; http://dx.doi.org/10.1289/ehp

  16. Obesity, expression of adipocytokines, and macrophage infiltration in canine mammary tumors.

    PubMed

    Lim, H Y; Im, K S; Kim, N H; Kim, H W; Shin, J I; Sur, J H

    2015-03-01

    Obesity influences the development, progression and prognosis of human breast cancer and canine mammary cancer (MC) but the precise underlying mechanism is not well-documented in the fields of either human or veterinary oncology. In the present study, the expression of major adipocytokines, including leptin, adiponectin, and leptin receptor (ObR) in benign (n = 28) and malignant (n = 70) canine mammary tumors was investigated by immunohistochemistry and on the basis of the subject's body condition score (BCS). To evaluate the relationship between obesity and chronic inflammation of the mammary gland, macrophages infiltrating within and around tumoral areas were counted. The mean age of MC development was lower in overweight or obese dogs (9.0 ± 1.8 years) than in lean dogs or optimal bodyweight (10.2 ± 2.9 years), and the evidence of lymphatic invasion of carcinoma cells was found more frequently in overweight or obese group than in lean or optimal groups. Decreased adiponectin expression and increased macrophage numbers in overweight or obese subjects were significantly correlated with factors related to a poor prognosis, such as high histological grade and lymphatic invasion. Leptin expression was correlated with progesterone receptor status, and ObR expression was correlated with estrogen receptor status of MCs, regardless of BCS. Macrophage infiltration within and around the tumor may play an important role in tumor progression and metastasis in obese female dogs and may represent a prognostic factor for canine MCs. PMID:25641553

  17. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss

    PubMed Central

    Arun, Gayatri; Diermeier, Sarah; Akerman, Martin; Chang, Kung-Chi; Wilkinson, J. Erby; Hearn, Stephen; Kim, Youngsoo; MacLeod, A. Robert; Krainer, Adrian R.; Norton, Larry; Brogi, Edi; Egeblad, Mikala; Spector, David L.

    2016-01-01

    Genome-wide analyses have identified thousands of long noncoding RNAs (lncRNAs). Malat1 (metastasis-associated lung adenocarcinoma transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genetic loss or systemic knockdown of Malat1 using antisense oligonucleotides (ASOs) in the MMTV (mouse mammary tumor virus)-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by significant differentiation into cystic tumors and a reduction in metastasis. Furthermore, Malat1 loss results in a reduction of branching morphogenesis in MMTV-PyMT- and Her2/neu-amplified tumor organoids, increased cell adhesion, and loss of migration. At the molecular level, Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and protumorigenic signaling pathways. Together, these data demonstrate for the first time a functional role of Malat1 in regulating critical processes in mammary cancer pathogenesis. Thus, Malat1 represents an exciting therapeutic target, and Malat1 ASOs represent a potential therapy for inhibiting breast cancer progression. PMID:26701265

  18. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss.

    PubMed

    Arun, Gayatri; Diermeier, Sarah; Akerman, Martin; Chang, Kung-Chi; Wilkinson, J Erby; Hearn, Stephen; Kim, Youngsoo; MacLeod, A Robert; Krainer, Adrian R; Norton, Larry; Brogi, Edi; Egeblad, Mikala; Spector, David L

    2016-01-01

    Genome-wide analyses have identified thousands of long noncoding RNAs (lncRNAs). Malat1 (metastasis-associated lung adenocarcinoma transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genetic loss or systemic knockdown of Malat1 using antisense oligonucleotides (ASOs) in the MMTV (mouse mammary tumor virus)-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by significant differentiation into cystic tumors and a reduction in metastasis. Furthermore, Malat1 loss results in a reduction of branching morphogenesis in MMTV-PyMT- and Her2/neu-amplified tumor organoids, increased cell adhesion, and loss of migration. At the molecular level, Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and protumorigenic signaling pathways. Together, these data demonstrate for the first time a functional role of Malat1 in regulating critical processes in mammary cancer pathogenesis. Thus, Malat1 represents an exciting therapeutic target, and Malat1 ASOs represent a potential therapy for inhibiting breast cancer progression. PMID:26701265

  19. Effect of medroxyprogesterone acetate on the response of the rat mammary gland to carcinogenesis.

    PubMed Central

    Russo, I. H.; Gimotty, P.; Dupuis, M.; Russo, J.

    1989-01-01

    In order to determine whether mammary gland differentiation, which is known to protect this organ from chemically induced carcinogenesis, can be stimulated in virgin rats by administration of a progestagenic agent, medroxyprogesterone acetate (MPA) was given to 300 Sprague-Dawley virgin rats, which at the ages of 45, 55, 65 and 75 days, groups I, II, III and IV respectively, had implanted an MPA pellet of 0.5 mg (low dose-LD) or 5.0 mg (high dose-HD). Pellets were removed after 21 days, and 21 days later five animals per group were killed for evaluation of mammary gland development. The remaining animals received 8 mg 7,12-dimethylbenz(a)-anthracene (DMBA) per 100 g body weight, and were killed after 24 weeks for evaluation of tumour incidence. Both age and treatment affected mammary gland structure and had a significant interaction in the proportion of terminal end buds (TEBs) present. The number of TEBs decreased as a function of age; treatment at both LD and HD did not modify the proportion of TEBs in groups I and III; LD decreased their percentage in group II, and both doses markedly increased TEB percentage in group IV animals. MPA LD treatment did not affect overall tumour and adenocarcinoma incidence although group IV animals developed greater incidences than their respective controls. MPA HD treated rats were 2.45 times more likely to develop tumours than their respective controls. Adenocarcinoma incidence had a significant positive correlation with the percentage of TEBs present. It was concluded that this progestagenic agent did not increase the risk of carcinoma development when administered to virgin rats at the clinical dose used for contraception. However, a 10-fold dose increase resulted in a higher tumorigenic response. PMID:2522791

  20. B and T cells are required for mouse mammary tumor virus spread within the mammary gland.

    PubMed

    Golovkina, T V; Dudley, J P; Ross, S R

    1998-09-01

    Mouse mammary tumor virus (MMTV) is an infectious retrovirus transmitted through milk from mother to newborns. MMTV encodes a superantigen (SAg) whose activity is indispensable for the virus life cycle, since a genetically engineered virus with a mutation in the sag gene neither amplified in cells of the immune system of suckling pups nor infected their mammary glands. When wild-type MMTV was injected directly into the mammary glands of uninfected pubescent mice, their lymphoid as well as mammary gland cells became virus infected. To test whether this infection of lymphoid cells was dependent on SAg activity and required for virus spread within the mammary gland, we performed mammary gland injections of wild-type MMTV(C3H) into two strains of transgenic mice that lacked SAg-cognate, V beta 14+ T cells. Neither the MTV-ORF or LEL strains showed infection of their mammary glands. Moreover, no MMTV infection of their peripheral lymphocytes was detected. Similar experiments with mice lacking B cells (mu-chain knockouts) showed no detectable virus spread in the mammary glands or lymphoid tissues. These data suggest that SAg activity and MMTV-infected lymphocytes are required, not only for initial steps of viral infection, but also for virus spread within the mammary gland. Virus spread at late times in infection determines whether MMTV induces mammary tumors. PMID:9725233

  1. Columnar cell lesions of the canine mammary gland: pathological features and immunophenotypic analysis

    PubMed Central

    2010-01-01

    Background It has been suggested that columnar cell lesions indicate an alteration of the human mammary gland involved in the development of breast cancer. They have not previously been described in canine mammary gland. The aim of this paper is describe the morphologic spectrum of columnar cell lesions in canine mammary gland specimens and their association with other breast lesions. Methods A total of 126 lesions were subjected to a comprehensive morphological review based upon the human breast classification system for columnar cell lesions. The presence of preinvasive (epithelial hyperplasia and in situ carcinoma) and invasive lesions was determined and immunophenotypic analysis (estrogen receptor (ER), progesterone receptor (PgR), high molecular weight cytokeratin (34βE-12), E-cadherin, Ki-67, HER-2 and P53) was perfomed. Results Columnar cell lesions were identified in 67 (53.1%) of the 126 canine mammary glands with intraepithelial alterations. They were observed in the terminal duct lobular units and characterized at dilated acini may be lined by several layers of columnar epithelial cells with elongated nuclei. Of the columnar cell lesions identified, 41 (61.2%) were without and 26 (38.8%) with atypia. Association with ductal hyperplasia was observed in 45/67 (67.1%). Sixty (89.5%) of the columnar cell lesions coexisted with neoplastic lesions (20 in situ carcinomas, 19 invasive carcinomas and 21 benign tumors). The columnar cells were ER, PgR and E-cadherin positive but negative for cytokeratin 34βE-12, HER-2 and P53. The proliferation rate as measured by Ki-67 appeared higher in the lesions analyzed than in normal TDLUs. Conclusions Columnar cell lesions in canine mammary gland are pathologically and immunophenotypically similar to those in human breast. This may suggest that dogs are a suitable model for the comparative study of noninvasive breast lesions. PMID:20178635

  2. Mammary gland neoplasia in long-term rodent studies.

    PubMed Central

    Russo, I H; Russo, J

    1996-01-01

    Breast cancer, the most frequent spontaneous malignancy diagnosed in women in the western world, is continuously increasing in incidence in industrialized nations. Although breast cancer develops in women as the result of a combination of external and endogenous factors such as exposure to ionizing radiation, diet, socioeconomic status, and endocrinologic, familial, or genetic factors, no specific etiologic agent(s) or the mechanisms responsible of the disease has been identified as yet. Thus, experimental models that exhibit the same complex interactions are needed for testing various mechanisms and for assessing the carcinogenic potential of given chemicals. Rodent mammary carcinomas represent such a model to a great extent because, in these species, mammary cancer is a multistep complex process that can be induced by either chemicals, radiation, viruses, or genetic factors. Long-term studies in rodent models have been particularly useful for dissecting the initiation, promotion, and progression steps of carcinogenesis. The susceptibility of the rodent mammary gland to develop neoplasms has made this organ a unique target for testing the carcinogenic potential of specific genotoxic chemicals and environmental agents. Mammary tumors induced by indirect- or direct-acting carcinogens such as 7, 12-dimethlbenz(a)anthracene or N-methyl-N-nitrosourea are, in general, hormone dependent adenocarcinomas whose incidence, number of tumors per animal, tumor latency, and tumor type are influenced by the age, reproductive history, and endocarinologic milieu of the host at the time of carcinogen exposure. Rodent models are informative in the absence of human data. They have provided valuable information on the dose and route of administration to be used and optimal host conditions for eliciting maximal tumorigenic response. Studies of the influence of normal gland development on the pathogenesis of chemically induced mammary carcinomas have clarified the role of differentiation

  3. Mouse mammary tumor biology: a short history.

    PubMed

    Cardiff, Robert D; Kenney, Nicholas

    2007-01-01

    For over a century, mouse mammary tumor biology and the associated Mouse mammary tumor virus (MMTV) have served as the foundation for experimental cancer research, in general, and, in particular, experimental breast cancer research. Spontaneous mouse mammary tumors were the basis for studies of the natural history of neoplasia, oncogenic viruses, host responses, endocrinology, and neoplastic progression. However, lacking formal proof of a human mammary tumor virus, the preeminence of the mouse model faded in the 1980s. Since the late 1980s, genetically engineered mice (GEM) have proven extremely useful for studying breast cancer and have become the animal model for human breast cancer. Hundreds of mouse models of human breast cancer have been developed since the first demonstration, in 1984, that the mouse mammary gland could be molecularly targeted and used to test the oncogenicity of candidate human genes. Now, very few scientists can avoid using a mouse model to test the biology of their favorite gene. The GEM have attracted a new generation of molecular and cellular biologists eager to apply their skills to these surrogates of the human disease. Newcomers often enter the field without an appreciation of the origins of mouse mammary tumor biology and the basis for many of the prevailing concepts. Our purpose in writing this short history of mouse mammary tumor biology is to provide a historical perspective for the benefit of the newcomers. If Einstein was correct in that "we stand on the shoulders of giants," the neophytes should meet their giants. PMID:17433908

  4. Mammary gland tumors in captive African hedgehogs.

    PubMed

    Raymond, J T; Gerner, M

    2000-04-01

    From December 1995 to July 1999, eight mammary gland tumors were diagnosed in eight adult captive female African hedgehogs (Atelerix albiventris). The tumors presented as single or multiple subcutaneous masses along the cranial or caudal abdomen that varied in size for each hedgehog. Histologically, seven of eight (88%) mammary gland tumors were malignant. Tumors were classified as solid (4 cases), tubular (2 cases), and papillary (2 cases). Seven tumors had infiltrated into the surrounding stroma and three tumors had histologic evidence of neoplastic vascular invasion. Three hedgehogs had concurrent neoplasms. These are believed to be the first reported cases of mammary gland tumors in African hedgehogs. PMID:10813628

  5. The ESR1 gene is associated with risk for canine mammary tumours

    PubMed Central

    2013-01-01

    Background The limited within-breed genetic heterogeneity and an enrichment of disease-predisposing alleles have made the dog a very suitable model for the identification of genes associated with risk for specific diseases. Canine mammary cancer is an example of such a disease. However, the underlying inherited risk factors for canine mammary tumours (CMTs) are still largely unknown. In this study, 52 single nucleotide polymorphisms (SNPs) in ten human cancer-associated genes were genotyped in two different datasets in order to identify genes/alleles associated with the development of CMTs. The first dataset consisted of English Springer Spaniel (ESS) CMT cases and controls. ESS is a dog breed known to be at increased risk of developing CMTs. In the second dataset, dogs from breeds known to have a high frequency of CMTs were compared to dogs from breeds with a lower occurrence of these tumours. Results We found significant associations to CMT for SNPs and haplotypes in the estrogen receptor 1 (ESR1) gene in the ESS material (best PBonf = 0.021). A large number of SNPs, among them several SNPs in ESR1, showed significantly different allele frequencies between the high and low risk breed groups (best PBonf = 8.8E-32, best PBPerm = 0.076). Conclusions The identification of CMT-associated SNPs in ESR1 in two independent datasets suggests that this gene might be involved in CMT development. These findings also support that CMT may serve as a good model for human breast cancer research. PMID:23574728

  6. Aberrant expressions of c-KIT and DOG-1 in mucinous and nonmucinous colorectal carcinomas and relation to clinicopathologic features and prognosis.

    PubMed

    Foda, Abd Al-Rahman Mohammad; Mohamed, Mie Ali

    2015-10-01

    c-KIT and DOG-1 are 2 highly expressed proteins in gastrointestinal stromal tumors. Few studies had investigated c-KIT, but not DOG-1, expression in colorectal carcinoma (CRC). This study aims to investigate expressions of c-KIT and DOG-1 in colorectal mucinous carcinoma and nonmucinous carcinoma using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique, and immunohistochemistry for c-KIT and DOG-1 was done. We found that aberrant c-KIT expression was detected in 12 cases (8%); 6 cases (4%) showed strong expression. Aberrant DOG-1 expression was detected in 15 cases (10%); among them, only 4 cases (2.7%) showed strong expression. Nonmucinous adenocarcinoma showed a significantly high expression of c-KIT, but not DOG-1, than MA. Aberrant c-KIT and DOG-1 expressions were significantly unrelated but were associated with excessive microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. In conclusion, aberrant c-KIT and DOG-1 expressions in CRC are rare events, either in NMA or MA. Nonmucinous adenocarcinoma showed a significantly higher expression of c-KIT, but not DOG-1, than MA. The expressions of both in CRC are significantly unrelated but are associated with microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. So, c-KIT and DOG-1 immunostaining is not a cost-effective method of identifying patients with CRC who may benefit from treatment with tyrosine kinase inhibitors. PMID:26272691

  7. Mammary myofibrosarcoma: case report and literature review.

    PubMed

    Stark, Matthew; Hoffmann, Andrew; Xiong, Zhenggang

    2011-01-01

    A case of myofibrosarcoma of breast is reported. A female patient aged 81 years presented with a mammary mass lesion. Histologically, the tumor consisted of neoplastic spindle cells arranged in fascicles and with variably cellularity and hyalinization. Immunohistochemical studies showed expression of vimentin, smooth-muscle actin, and Bcl-2, but not desmin, S-100, C-kit, or CD34. Proliferative index identified by Ki67 was approximately 30%. Electron microscopy revealed variable amount of rough endoplasmic reticulum, myofilaments, fibronexus junctions, and fibronectin fibrils. The histological, immunohistochemical, and ultrastructural features of this tumor were consistent with myofibrosarcoma. This case will be one of the very few cases of ultrastructurally confirmed mammary myofibrosarcoma reported in the literature and contributes to the recognition of this rare mammary malignant neoplasm. The literature on mammary myofibrosarcoma and its differential diagnosis is also reviewed. PMID:21545434

  8. A Case of Pigmented Mammary Paget's Disease

    PubMed Central

    Kim, Ji Eun; Kang, Myung Seung; Kim, Joung Soo

    2008-01-01

    Pigmented mammary Paget's disease is a uncommon clinicopathologic variant of mammary Paget's disease, and this mimics malignant melanoma both clinically and histopathologically. Herein, we report on a rare case of pigmented mammary Paget's disease. An 81-year-old woman presented with 2.5×1 cm sized, red and brown, eczematous plaque on her right areola, and she'd had this lesion for 3 years. Histopathology showed large, atypical cells with large nuclei and abundant pale cytoplasm throughout the epidermis. Dispersed melanocytes were noted in the epidermis and some of the Paget's cells contained melanin within their cytoplasm. Immunohistochemical studies demonstrated that the intraepidermal pagetoid cells were positive for cytokeratin 7; in contrast, they were negative for S-100, Periodic-acid Schiff (PAS), Alcian blue at PH 2.5, HMB-45 and carninoembryonic antigen (CEA). We recommend that pigmented mammary Paget's disease should be included in the differential diagnosis of pigmented lesions on the nipple. PMID:27303202

  9. Gordon Research Conference on Mammary Gland Biology

    SciTech Connect

    Not Available

    1989-01-01

    The 1989 conference was the tenth in the series of biennial Gordon Research Conferences on Mammary Gland Biology. Traditionally this conference brings together scientists from diverse backgrounds and experience but with a common interest in the biology of the mammary gland. Investigators from agricultural and medical schools, biochemists, cell and molecular biologists, endocrinologists, immunologists, and representatives from the emerging biotechnology industries met to discuss current concepts and results on the function and regulation of the normal and neoplastic mammary gland in a variety of species. Of the participants, approximately three-fourths were engaged in studying the normal mammary gland function, whereas the other quarter were engaged in studying the neoplastic gland. The interactions between scientists, clinicians, veterinarians examining both normal and neoplastic cell function serves to foster the multi-disciplinary goals of the conference and has stimulated many cooperative projects among participants in previous years.

  10. Lipid Transport in the Lactating Mammary Gland

    PubMed Central

    McManaman, James L.

    2015-01-01

    Mammalian cells depend on phospholipid (PL) and fatty acid (FA) transport to maintain membrane structure and organization, and to fuel and regulate cellular functions. In mammary glands of lactating animals, copious milk secretion, including large quantities of lipid in some species, requires adaptation and integration of PL and FA synthesis and transport processes to meet secretion demands. At present few details exist about how these processes are regulated within the mammary gland. However, recent advances in our understanding of the structural and molecular biology of membrane systems and cellular lipid trafficking provide insights into the mechanisms underlying the regulation and integration of PL and FA transport processes the lactating mammary gland. This review discusses the PL and FA transport processes required to maintain the structural integrity and organization of the mammary gland and support its secretory functions within the context of current molecular and cellular models of their regulation. PMID:24567110

  11. DogMATIC--A Remote Biospecimen Collection Kit for Biobanking.

    PubMed

    Milley, Kristi M; Nimmo, Judith S; Bacci, Barbara; Ryan, Stewart D; Richardson, Samantha J; Danks, Janine A

    2015-08-01

    Canine tumors are valuable comparative oncology models. This research was designed to create a sustainable biobank of canine mammary tumors for breast cancer research. The aim was to provide a well-characterized sample cohort for specimen sharing, data mining, and long-term research aims. Canine mammary tumors are most frequently managed at a local veterinary clinic or hospital. We adopted a biobank framework based on a large number of participating veterinary hospitals and clinics acting as collection centers that were serviced by a centralized storage facility. Recruitment was targeted at rural veterinary clinics. A tailored, stable collection kit (DogMATIC) was designed that was used by veterinarians in remote or rural locations to collect both fresh and fixed tissue for submission to the biobank. To validate this methodology the kit design, collection rate, and sample quality were analyzed. The Australian Veterinary Cancer Biobank was established as a network of 47 veterinary clinics and three veterinary pathology laboratories spanning over 200,000 km(2). In the first 12 months, 30 canine mammary tumor cases were submitted via the DogMATIC kit. Pure intact RNA was isolated in over 80% of samples with an average yield of 14.49 μg. A large network biobank, utilizing off-site collection with the DogMATIC kit, was successfully coordinated. The creation of the Australian Veterinary Cancer Biobank has established a long-term, sustainable, comparative oncology research resource in Australia. There are broader implications for biobanking with this very different form of collection and banking. PMID:26186583

  12. Bacterial colonization of the ovarian bursa in dogs with clinically suspected pyometra and in controls.

    PubMed

    Rubio, Alejandro; Boyen, Filip; Tas, Olaf; Kitshoff, Adriaan; Polis, Ingeborgh; Van Goethem, Bart; de Rooster, Hilde

    2014-10-15

    Septic peritonitis occurs relatively commonly in dogs. Secondary septic peritonitis is usually associated with perforation of intestines or infected viscera, such as the uterus in pyometra cases. The aim of this study was to evaluate the bacterial flora in the ovarian bursae of intact bitches as a potential source of contamination. One hundred forty dogs, clinically suspected of pyometra, were prospectively enrolled. The control group consisted of 26 dogs that underwent elective ovariohysterectomies and 18 dogs with mammary gland tumors that were neutered at the time of mastectomy. Bacteriology samples were taken aseptically at the time of surgery from the bursae and the uterus in all dogs. Twenty-two dogs that were clinically suspected of pyometra had sterile uterine content ("mucometra" cases); the remaining 118 had positive uterine cultures ("pyometra" cases) and septic peritoneal fluid was present in 10% of these cases. Of the 118 pyometra cases, 9 had unilateral and 15 had bilateral bacterial colonization of their ovarian bursae. However, the bacteria from the ovarian bursa were similar to those recovered from the uterine pus in only half of the cases. Furthermore, positive bursae were also seen in one mucometra dog (unilateral) and in four control dogs (two unilateral and two bilateral). The data illustrate that the canine ovarian bursa can harbor bacteria. The biological importance of these isolations remains unclear. PMID:25127745

  13. Mammary Adipose Tissue-Derived Lysophospholipids Promote Estrogen Receptor-Negative Mammary Epithelial Cell Proliferation.

    PubMed

    Volden, Paul A; Skor, Maxwell N; Johnson, Marianna B; Singh, Puneet; Patel, Feenalie N; McClintock, Martha K; Brady, Matthew J; Conzen, Suzanne D

    2016-05-01

    Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein-coupled receptors, has been implicated in many physiologic and pathologic processes, including cancer. LPA is converted from lysophosphatidylcholine (LPC) by the secreted phospholipase autotaxin (ATX). Although various cell types can produce ATX, adipocyte-derived ATX is believed to be the major source of circulating ATX and also to be the major regulator of plasma LPA levels. In addition to ATX, adipocytes secrete numerous other factors (adipokines); although several adipokines have been implicated in breast cancer biology, the contribution of mammary adipose tissue-derived LPC/ATX/LPA (LPA axis) signaling to breast cancer is poorly understood. Using murine mammary fat-conditioned medium, we investigated the contribution of LPA signaling to mammary epithelial cancer cell biology and identified LPA signaling as a significant contributor to the oncogenic effects of the mammary adipose tissue secretome. To interrogate the role of mammary fat in the LPA axis during breast cancer progression, we exposed mammary adipose tissue to secreted factors from estrogen receptor-negative mammary epithelial cell lines and monitored changes in the mammary fat pad LPA axis. Our data indicate that bidirectional interactions between mammary cancer cells and mammary adipocytes alter the local LPA axis and increase ATX expression in the mammary fat pad during breast cancer progression. Thus, the LPC/ATX/LPA axis may be a useful target for prevention in patients at risk of ER-negative breast cancer. Cancer Prev Res; 9(5); 367-78. ©2016 AACR. PMID:26862086

  14. Localization of heat shock protein 110 in canine mammary gland tumors.

    PubMed

    Okada, Satoru; Furuya, Masaru; Takenaka, Shigeo; Fukui, Ayano; Matsubayashi, Makoto; Tani, Hiroyuki; Sasai, Kazumi

    2015-10-15

    Heat shock proteins (HSPs) function as molecular chaperones in the regulation of protein folding, conformation, and assembly; in addition, they also protect cells from protein-protein aggregation resulting from cellular stress. Recently, HSPs were shown to be overexpressed in several human cancer cells compared with normal cells. HSPs are considered to be related to apoptosis-associated proteins, and inhibition of apoptosis promotes tumor growth. Canine mammary gland tumors have received a great deal of attention from researchers due to the many common biological and histological characteristics that they share with human tumors. We previously confirmed that HSP110 is a canine mammary gland tumor antigen and reported that HSP110 mRNA expression significantly increased in tumor tissue. We have now created a functional recombinant canine HSP110 protein and a rabbit anti-HSP110 polyclonal antibody. This recombinant protein can refold heat-denatured firefly luciferase at 42°C. Immunohistochemical analysis showed that HSP110 was mainly localized in the cytoplasm of epithelial and interstitial cells in canine mammary gland tumors. Extensive genomic research has revealed genetic similarities between humans and dogs; comparative oncological studies between these species have made remarkable progress. The results reported here contribute valuable oncological knowledge for the development of novel therapeutic methods in both veterinary science and human medicine. PMID:26292766

  15. Prognostic value of regional lymph node status in canine mammary carcinomas.

    PubMed

    Szczubiał, M; Łopuszynski, W

    2011-12-01

    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. PMID:22077411

  16. Effect of adjuvant perioperative desmopressin in locally advanced canine mammary carcinoma and its relation to histologic grade.

    PubMed

    Hermo, Guillermo A; Turic, Esteban; Angelico, Daniel; Scursoni, Alejandra M; Gomez, Daniel E; Gobello, Cristina; Alonso, Daniel F

    2011-01-01

    Desmopressin (DDAVP) is a vasopressin peptide analog with hemostatic properties that has been successfully used during surgery in patients with bleeding disorders. Recently published experimental and clinical data indicate that perioperative administration of DDAVP can minimize spread and survival of residual mammary cancer cells. The central aim of this study was to explore the effect of perioperative DDAVP and its relation to histologic grade in bitches with locally advanced mammary carcinoma. Of the 32 dogs initially recruited, 28 intact bitches with mammary carcinoma tumors stage III or IV were ultimately included. These dogs were randomized to receive DDAVP at intravenous doses of 1 μg/kg (n=18) or saline solution as placebo (n=10). En bloc mastectomy of the affected gland(s) was performed. Tumor malignancy was graded by the method of Elston and Ellis into well-differentiated (grade 1), moderately differentiated (grade 2), or poorly differentiated (grade 3). DDAVP therapy significantly prolonged the disease-free survival (P<0.001) and overall survival (P<0.01) in bitches with grade 2 or 3 carcinomas compared with bitches in the control group. No significant difference in disease-free period or overall survival was found between treatment groups in bitches with grade 1 tumors. The present data suggest that DDAVP may be an excellent candidate as a surgical adjuvant in the management of aggressive cancers in small animals. More research in this field is warranted. PMID:21164169

  17. Endometrioid endometrial adenocarcinoma recurring as carcinosarcoma.

    PubMed

    Shaco-Levy, Ruthy; Piura, Benjamin

    2008-04-01

    Müllerian carcinosarcoma is currently regarded as a metaplastic (sarcomatous) carcinoma. Only five cases of pure ovarian adenocarcinoma recurring as carcinosarcoma have been documented in the literature. There are no documented cases of endometrial adenocarcinoma recurring as metaplastic carcinoma. We report of a case of endometrial adenocarcinoma, endometrioid type, recurring as metaplastic carcinoma showing sarcomatous differentiation. The tumor evolution in this case supports the prevailing opinion that Müllerian carcinosarcomas are derived from carcinomas and represent tumor progression. PMID:18412798

  18. Genome-Wide Analysis Identifies Germ-Line Risk Factors Associated with Canine Mammary Tumours

    PubMed Central

    Melin, Malin; Murén, Eva; Gustafson, Ulla; Starkey, Mike; Borge, Kaja Sverdrup; Lingaas, Frode; Saellström, Sara; Rönnberg, Henrik; Lindblad-Toh, Kerstin

    2016-01-01

    Canine mammary tumours (CMT) are the most common neoplasia in unspayed female dogs. CMTs are suitable naturally occurring models for human breast cancer and share many characteristics, indicating that the genetic causes could also be shared. We have performed a genome-wide association study (GWAS) in English Springer Spaniel dogs and identified a genome-wide significant locus on chromosome 11 (praw = 5.6x10-7, pperm = 0.019). The most associated haplotype spans a 446 kb region overlapping the CDK5RAP2 gene. The CDK5RAP2 protein has a function in cell cycle regulation and could potentially have an impact on response to chemotherapy treatment. Two additional loci, both on chromosome 27, were nominally associated (praw = 1.97x10-5 and praw = 8.30x10-6). The three loci explain 28.1±10.0% of the phenotypic variation seen in the cohort, whereas the top ten associated regions account for 38.2±10.8% of the risk. Furthermore, the ten GWAS loci and regions with reduced genetic variability are significantly enriched for snoRNAs and tumour-associated antigen genes, suggesting a role for these genes in CMT development. We have identified several candidate genes associated with canine mammary tumours, including CDK5RAP2. Our findings enable further comparative studies to investigate the genes and pathways in human breast cancer patients. PMID:27158822

  19. Genome-Wide Analysis Identifies Germ-Line Risk Factors Associated with Canine Mammary Tumours.

    PubMed

    Melin, Malin; Rivera, Patricio; Arendt, Maja; Elvers, Ingegerd; Murén, Eva; Gustafson, Ulla; Starkey, Mike; Borge, Kaja Sverdrup; Lingaas, Frode; Häggström, Jens; Saellström, Sara; Rönnberg, Henrik; Lindblad-Toh, Kerstin

    2016-05-01

    Canine mammary tumours (CMT) are the most common neoplasia in unspayed female dogs. CMTs are suitable naturally occurring models for human breast cancer and share many characteristics, indicating that the genetic causes could also be shared. We have performed a genome-wide association study (GWAS) in English Springer Spaniel dogs and identified a genome-wide significant locus on chromosome 11 (praw = 5.6x10-7, pperm = 0.019). The most associated haplotype spans a 446 kb region overlapping the CDK5RAP2 gene. The CDK5RAP2 protein has a function in cell cycle regulation and could potentially have an impact on response to chemotherapy treatment. Two additional loci, both on chromosome 27, were nominally associated (praw = 1.97x10-5 and praw = 8.30x10-6). The three loci explain 28.1±10.0% of the phenotypic variation seen in the cohort, whereas the top ten associated regions account for 38.2±10.8% of the risk. Furthermore, the ten GWAS loci and regions with reduced genetic variability are significantly enriched for snoRNAs and tumour-associated antigen genes, suggesting a role for these genes in CMT development. We have identified several candidate genes associated with canine mammary tumours, including CDK5RAP2. Our findings enable further comparative studies to investigate the genes and pathways in human breast cancer patients. PMID:27158822

  20. Dogs recognize dog and human emotions.

    PubMed

    Albuquerque, Natalia; Guo, Kun; Wilkinson, Anna; Savalli, Carine; Otta, Emma; Mills, Daniel

    2016-01-01

    The perception of emotional expressions allows animals to evaluate the social intentions and motivations of each other. This usually takes place within species; however, in the case of domestic dogs, it might be advantageous to recognize the emotions of humans as well as other dogs. In this sense, the combination of visual and auditory cues to categorize others' emotions facilitates the information processing and indicates high-level cognitive representations. Using a cross-modal preferential looking paradigm, we presented dogs with either human or dog faces with different emotional valences (happy/playful versus angry/aggressive) paired with a single vocalization from the same individual with either a positive or negative valence or Brownian noise. Dogs looked significantly longer at the face whose expression was congruent to the valence of vocalization, for both conspecifics and heterospecifics, an ability previously known only in humans. These results demonstrate that dogs can extract and integrate bimodal sensory emotional information, and discriminate between positive and negative emotions from both humans and dogs. PMID:26763220

  1. Spleen tyrosine kinase regulates mammary epithelial cell proliferation in mammary glands of dairy cows.

    PubMed

    Hou, Xiaoming; Lin, Lin; Xing, Weinan; Yang, Yang; Duan, Xiaoyu; Li, Qingzhang; Gao, Xuejun; Lin, Ye

    2016-05-01

    Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase that has been considered a hematopoietic cell-specific signal transducer involved in cell proliferation and differentiation. However, the role of SYK in normal mammary gland is still poorly understood. Here we show that SYK is expressed in mammary glands of dairy cows. Expression of SYK was higher in dry period mammary tissues than in lactating mammary tissues. Knockdown and overexpression of SYK affected dairy cow mammary epithelial cell proliferation as well as the expression of signal molecules involved in proliferation, including protein kinase B (PKB, also known as AKT1), p42/44 mitogen-activated protein kinase (MAPK), and signal transducer and activator of transcription 5 (STAT5). Dual-luciferase reporter assay showed that SYK increased the transcriptional activity of the AKT1 promoter, and cis-elements within the AKT1 promoter region from -439 to -84 bp mediated this regulation. These results suggest that SYK affects mammary epithelial cell proliferation by activating AKT1 at the transcriptional level in mammary glands of dairy cows, which is important for the mammary remodeling process in dry cows as well as for increasing persistency of lactation in lactating cows. PMID:26947307

  2. Mammary gland involution is associated with rapid down regulation of major mammary Ca**2+-ATPases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sixty percent of calcium in milk is transported across the mammary cells apical membrane by the plasma membrane Ca**2+-ATPase 2 (PMCA2). The effect of abrupt cessation of milk production on the Ca**2+-ATPases and mammary calcium transport is unknown. We found that 24 hours after stopping milk prod...

  3. Morphological and histological characteristics of mammary dysplasias occurring in cell dissociation-derived murine mammary outgrowths

    SciTech Connect

    Ethier, S.P.; Adams, L.M.; Ullrich, R.L.

    1984-10-01

    The morphological and histological characteristics of ductal dysplasias that were observed in mammary outgrowths derived from monodispersed mammary cells of carcinogen-treated mice are described. Mammary outgrowths were derived by injecting either 10(4) or 10(5) enzymatically dissociated mammary cells, obtained from control or carcinogen-treated BALB/c mice, into gland-free mammary fat pads of syngeneic hosts. The mammary dysplasias observed varied considerably in morphological and histological characteristics. The majority of the lesions were ductal in origin and were associated with epithelial hyperplasia which ranged from mild hyperplasia, in which only a few extra layers of epithelium were present, to severe hyperplasia, in which the ducts and end buds were occluded and distended with epithelial cells. In addition, papillary and lobular lesions were observed which were also associated with varying degrees of hyperplasia. The range of mammary dysplasias observed in these outgrowths closely resembles that of lesions associated with the pathogenesis of mammary carcinoma in mice, rats, and humans.

  4. Multiple RT-PCR markers for the detection of circulating tumour cells of metastatic canine mammary tumours.

    PubMed

    da Costa, A; Kohn, B; Gruber, A D; Klopfleisch, R

    2013-04-01

    In humans, detection of circulating tumour cells (CTCs) using nucleic acid-based methods such as reverse transcription polymerase chain reaction (RT-PCR) has proven to be of prognostic relevance. However, similar procedures are still lacking in veterinary oncology. To assess the correlation of CTC markers with the metastatic potential of canine mammary tumours, 120 peripheral blood samples from bitches with mammary carcinomas with (group 1) and without (group 2) histological evidence of vascular invasion and/or presence of lymph node metastases and mammary adenomas (group 3) were analyzed. Blood samples were collected in EDTA tubes and RNA was extracted within 48 h. Subsequently, the samples were tested by RT-PCR for a panel of seven CTC mRNA markers. CRYAB was the most sensitive single marker with a sensitivity of 35% and also the most specific marker with a specificity of 100% to detect group 1 blood samples. A multimarker assay combining four genes enhanced the sensitivity up to 77.5%, but decreased the specificity to 80%. CRYAB appeared to be highly specific but only moderately sensitive at detecting blood samples from dogs with metastatic tumours and detection significantly correlated with vascular invasion of primary mammary tumours. However, a multimarker assay of four genes significantly enhanced the sensitivity of the assay and is therefore preferable for CTC detection. PMID:23036177

  5. The antiprogestins mifepristone and onapristone reduce cell proliferation in the canine mammary carcinoma cell line CMT-U27.

    PubMed

    Guil-Luna, Silvia; Hellmén, Eva; Sánchez-Céspedes, Raquel; Millán, Yolanda; Martín de las Mulas, Juana

    2014-07-01

    Canine mammary tumours (CMTs) represent nearly half of all tumours in female dogs and some 50% have malignant behaviour. Simple epithelial carcinomas have shorter disease free periods after surgery and a higher reduction of the proliferation index reduction after antiprogestin aglepristone treatment in vivo related to the expression of progesterone receptors (PR). These findings make simple carcinomas good candidates for endocrine therapy. To further explore this possibility, the effects of the antiprogestins mifepristone (RU486) and onapristone (ZK299) on cell viability and PR expression of the canine mammary carcinoma cell line isolated from a simple epithelial carcinoma CMT-U27 were studied. Twenty five percent of CMT-U27 control cells expressed PR. RU486 (p<0.05) and ZK299 (p<0.05) reduced the number of viable cells (WST-8 test) at 24h but only the latter treatment reduced significantly PR expression in viable tumour cells at 24h of incubation. The results suggest that both RU486 and ZK299 induce a decrease in the number of viable CMT-U27 tumour cells with different effects on PR expression. The canine mammary carcinoma cell line CMT-U27 is sensitive to the effects of antiprogestins and may serve to further explore the role of these drugs in canine mammary carcinomas. PMID:24500783

  6. Adenocarcinoma of the Dorsal Glands in 2 European Ground Squirrels (Spermophilus citellus)

    PubMed Central

    Carminato, Antonio; Nassuato, Chiara; Vascellari, Marta; Bozzato, Elisa; Mutinelli, Franco

    2012-01-01

    Olfactory communication is an important aspect of the biology of ground squirrels; accordingly, some of their integumentary glands are associated with scent-marking behavior. Although reports of neoplasms in ground squirrels are limited, the literature on tumors in this family of rodents is extensive, with hepatocellular carcinomas in woodchucks and fibromas in squirrels being the 2 most common neoplasms. Apocrine gland tumors occur frequently in domestic animals such as cats and dogs but to our knowledge have not previously been reported in squirrels. Here we describe 2 cases of adenocarcinoma of the dorsal glands in privately owned European ground squirrels (Spermophilus citellus). The skin nodules were characterized histologically by proliferation of epithelial cells, which were arranged in a tubuloacinar pattern with neoplastic emboli within the blood vessels. Adenocarcinoma of the dorsal glands was diagnosed in light of the anatomic localization, immunohistochemistry results, and histochemistry findings. PMID:23043780

  7. Identification of prognostic factors in canine mammary malignant tumours: a multivariable survival study

    PubMed Central

    2013-01-01

    Background Although several histopathological and clinical features of canine mammary gland tumours have been widely studied from a prognostic standpoint, considerable variations in tumour individual biologic behaviour difficult the definition of accurate prognostic factors. It has been suggested that the malignant behaviour of tumours is the end result of several alterations in cellular physiology that culminate in tumour growth and spread. Accordingly, the aim of this study was to determine, using a multivariable model, the independent prognostic value of several immunohistochemically detected tumour-associated molecules, such as MMP-9 and uPA in stromal cells and Ki-67, TIMP-2 and VEGF in cancer cells. Results Eighty-five female dogs affected by spontaneous malignant mammary neoplasias were followed up for a 2-year post-operative period. In univariate analysis, tumour characteristics such as size, mode of growth, regional lymph node metastases, tumour cell MIB-1 LI and MMP-9 and uPA expressions in tumour-adjacent fibroblasts, were associated with both survival and disease-free intervals. Histological type and grade were related with overall survival while VEGF and TIMP-2 were not significantly associated with none of the outcome parameters. In multivariable analysis, only a MIB-1 labelling index higher than 40% and a stromal expression of MMP-9 higher than 50% retained significant relationships with poor overall and disease-free survival. Conclusions The results of this study indicate that MMP-9 and Ki-67 are independent prognostic markers of canine malignant mammary tumours. Furthermore, the high stromal expressions of uPA and MMP-9 in aggressive tumours suggest that these molecules are potential therapeutic targets in the post-operative treatment of canine mammary cancer. PMID:23289974

  8. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed without..., swine, and goats shall not be saved for edible purposes. (d) The udders from cows officially...

  9. Paranuaclear E-cadherin in gastric adenocarcinoma.

    PubMed

    Carpenter, Philip M; Al-Kuran, Rasha A; Theuer, Charles P

    2002-12-01

    Decreased E-cadherin expression permits dissociation and widespread dissemination of gastric adenocarcinoma cells. We studied the relationship between paranuclear E-cadherin distribution and the histopathologic characteristics of gastric adenocarcinomas. E-cadherin immunostains of 173 gastric adenocarcinoma sections revealed paranuclear; punctate to vesicular staining in 18% (16/87) of the intestinal-type adenocarcinomas, 30% (17/56) of the diffuse-type adenocarcinomas, and 30% (9/30) of the mired adenocarcinomas. These data suggest that in some gastric adenocarcinomas, there is a defect in transport of E-cadherin to the cell surface, which may prevent intercellular adhesion and encourage dissemination. Of 34 cancers with paranuclear E-cadherin staining, 20 (59%) had paranuclear staining within the nonneoplastic epithelium, but only 22.0% of 100 carcinomas with absent or membranous E-cadherin staining were accompanied by morphologically benign epithelium with paranuclear E-cadherin. In surface epithelium, paranuclear E-cadherin staining colocalized with Griffonia simplicifolia lectin II in the Golgi apparatus. The presence of paranuclear E-cadherin in cancer-associated benign epithelium suggests that the alteration in the E-cadherin molecule responsible for the paranuclear distribution may be an early change in gastric adenocarcinoma progression. PMID:12472282

  10. Tularaemia in Norwegian dogs.

    PubMed

    Nordstoga, Anne; Handeland, Kjell; Johansen, Tone Bjordal; Iversen, Lena; Gavier-Widén, Dolores; Mattsson, Roland; Wik-Larssen, Kjersti; Afset, Jan Egil; Næverdal, Rune; Lund, Arve

    2014-10-10

    We describe tularaemia in a Norwegian dog caused by Francisella tularensis subspecies holarctica. A Hamilton Hound and his owner developed tulaeremia after hunting an infected mountain hare (Lepus timidus). The dog showed signs of lethargy, anorexia and fever during a period two to four days after hunting and thereafter fully recovered. Its antibody titers increased 32-fold from one to three weeks post exposure. Thereafter, the titer declined and leveled off at moderate positive values up to one year after exposure (end of study). This is believed to be the first case report of clinical F. tularensis subspecies holarctica infection in a European dog. In 2011, enormous numbers of Norway lemmings (Lemmus lemmus) occurred in Finnmark, the northernmost county of Norway and many dogs caught and swallowed lemmings. Some of these dogs developed non-specific signs of disease and the owners consulted a veterinary surgeon, who suspected tularaemia. In order to investigate this hypothesis, serum samples from 33 dogs were examined for antibodies to F. tularensis. The dogs were allocated into three groups: Dogs from Finnmark that became sick (Group 1) or remained healthy following contact with lemmings (Group 2), and healthy control dogs from Oslo without known contact with lemmings (Group 3). All the serum samples were analyzed with a tube agglutination assay. Among dogs exposed to lemmings, 10/11 and 3/12 were antibody positive in Group 1 and Group 2, respectively, whereas none of the control dogs (n=10) were positive for antibodies against F. tularensis. These results strongly indicate that the non-specific disease seen in the dogs in Finnmark was linked to F. tularensis infection acquired through contact with lemmings. PMID:25150161

  11. Conjunctival metastatic adenocarcinoma of unknown origin.

    PubMed

    Li, He J; Tsaousis, Konstantinos T; Hoopes, Phillip; Mamalis, Nick

    2016-01-01

    We describe the case of a presumed metastatic adenocarcinoma discovered in the conjunctival limbus of a 75-year-old male with a history of prostate adenocarcinoma. After an initial clinical diagnosis of pinguecula and unsuccessful topical steroid therapy, the lesion was excised and sent for pathological evaluation and special staining. The histopathological evaluation was consistent with a diagnosis of adenocarcinoma, without evidence of lacrimal tissue. Surprisingly, results from special staining were most consistent with lung adenocarcinoma rather than that from a prostate origin. Systemic radiographic evaluation did not locate the primary tumour, and the patient did not present with any symptoms consistent with malignancy. Watchful waiting was chosen as the therapeutic strategy to manage the patient. This is the first report of an adenocarcinoma, likely metastatic, at the conjunctival limbus. PMID:27190113

  12. Service dogs. Final rule.

    PubMed

    2012-09-01

    The Department of Veterans Affairs (VA) amends its regulations concerning veterans in need of service dogs. Under this final rule, VA will provide to veterans with visual, hearing, or mobility impairments benefits to support the use of a service dog as part of the management of such impairments. The benefits include assistance with veterinary care, travel benefits associated with obtaining and training a dog, and the provision, maintenance, and replacement of hardware required for the dog to perform the tasks necessary to assist such veterans. PMID:22950145

  13. A case of accessory mammary cancer in a male patient and a literature review.

    PubMed

    Gao, Y G; Zhang, S H; Wang, Y

    2014-01-01

    A 68-year-old Chinese male patient was referred to the present hospital because of a right axillary lump in May 2011. Physical examination showed a rigid movable mass measuring 35 mm in diameter in the right axilla. No mass was palpable in either breast. Mammograms were normal. Physical and imaging examination of the head and neck region, lung, and upper and lower gastrointestinal tract also revealed no evidence of a primary tumor. Ultrasonography and resonance imaging (MRI) revealed no evidence of tumors in the bilateral mammary glands. Fine needle histological biopsy for suspected malignancy was performed, and the patient underwent tumor resection with axillary lymph node dissection on Jun 2011. Moderately differentiated adenocarcinoma in ectopic breast tissue was diagnosed based on the pathologic result, the tumor was immunohistochemically positive for ER, PR, and HER-2. PMID:25118491

  14. Comparative aspects of mammary gland development and homeostasis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary glands are crucial to the reproductive strategy of mammals and the milk of domesticated ruminants serves as an important source of nutrients for the human population. The majority of mammary gland development occurs postnatally and the mammary gland undergoes cyclical periods of growth, dif...

  15. Abnormal structure of the canine oncogene, related to the human c-yes-1 oncogene, in canine mammary tumor tissue.

    PubMed

    Miyoshi, N; Tateyama, S; Ogawa, K; Yamaguchi, R; Kuroda, H; Yasuda, N; Shimizu, T

    1991-12-01

    Cellular oncogenes of genomic DNA in 6 canine primary mammary tumors were screened by Southern blot analysis, using 7 oncogene probes. A canine genomic oncogene related to the human c-yes-1 oncogene was detected as abnormal bands in solid carcinoma genomic DNA digested with EcoRI, HindIII, HindIII-EcoRI, or HindIII-BamHI. Comparison was made between other tumor specimens and control specimens obtained from 4 clinically normal dogs--1 mixed breed and 3 Shiba Inu dogs (the same breed as the dog from which the solid carcinoma was obtained). These abnormal bands were 0.1 to 1 kilobase shorter than the normal gene. However, digestion of genomic DNA obtained from normal WBC of this dog also produced all of the abnormal bands as observed in digested DNA from the solid carcinoma tissue. Therefore, in this dog, the genomic DNA of all somatic cells from the ontogenic stage still had the abnormal sequences related to the human c-yes-1 oncogene, and it is possible that this abnormal structure may have some role (eg, as an initiator) in tumorigenesis or the progression of this tumor. PMID:1789521

  16. Ability of bovine mammary macrophages to enhance proliferation of autologous blood and mammary secretion lymphocytes.

    PubMed

    Concha, C; Holmberg, O

    1990-02-01

    Cells were obtained by centrifuging the mammary secretion of healthy udders of 19 cows during the dry-period and during mid-lactation. The suspended cells were incubated in plastic wells. Those adhered cells classified as mammary macrophages were incubated with pokeweed mitogen (PWM). Autologous peripheral blood lymphocytes were added to wells containing untreated macrophage cultures or cultures pretreated with PWM. In seven cows autologous dry-period mammary lymphocytes were added instead of blood lymphocytes. The macrophages + lymphocyte cultures were subjected to the lymphocyte stimulation test (LST). For comparison, peripheral blood lymphocytes and dry-period secretion lymphocytes were also subjected to the LST in the presence of PWM. In all cases, mitogenic responses were higher in pretreated macrophage cultures than in background control cultures. The stimulation indices (SI) showed that PWM-pretreated dry-period mammary macrophages enhanced the proliferation of autologous peripheral blood lymphocytes to a greater extent than did blood lymphocytes plus PWM (49 +/- 10 v. 30 +/- 6; P less than or equal to 0.05). Mammary macrophages taken from the same cows but during midlactation also clearly induced proliferation of autologous peripheral blood lymphocytes but to a lesser extent than dry-period macrophages (16 +/- 2 v. 49 +/- 10; 16 +/- 2 v. 30 +/- 6; P less than or equal to 0.01 and P less than or equal to 0.05). The PWM pretreatment of mammary macrophages increased the proliferation of autologous dry-period mammary lymphocytes by at least a factor of three (28 +/- 8 v. 8 +/- 2 P less than or equal to 0.05). The present results indicate that bovine mammary macrophages pretreated with PWM enhance proliferation as well as modulation of mammary and peripheral blood lymphocytes. The modulation of lymphocyte stimulation as demonstrated here in vitro, has great significance regarding aspects of local immunostimulation related to modern treatment of mastitis. PMID

  17. Transforming growth factor-alpha promotes mammary tumorigenesis through selective survival and growth of secretory epithelial cells.

    PubMed Central

    Smith, G. H.; Sharp, R.; Kordon, E. C.; Jhappan, C.; Merlino, G.

    1995-01-01

    Transforming growth factor (TGF)-alpha stimulates the growth and development of mammary epithelial cells and is implicated in the pathogenesis of human breast cancer. In this report we evaluate the consequences of overexpressing TGF-alpha in the mammary gland of transgenic mice and examine associated cellular mechanisms. When operating on a FVB/N genetic background (line MT100), TGF-alpha induced the stochastic development of mammary adenomas and adenocarcinomas f secretory epithelial origin in 64% of multiparous females. In contrast, tumors were exceedingly rare in virgin MT100 females, MT100 males, and multiparous FVB/N females. In MT100 females multiple foci of hyperplastic secretory lesions preceded the development of frank tumors; these initial lesions appeared during the involution period after the first lactation. Serial transplantation of these hyperplasias indicated an absence of proliferative immortality. Nevertheless, they gave rise to tumors at a low frequency and after a prolonged latency in virgin hosts; in multiparous hosts, tumors developed earlier and at a high incidence. The TGF-alpha transgene was highly expressed in hyperplasias and tumors but not in virgin and nonlesion-bearing tissue, suggesting that TGF-alpha overexpression provides a selective growth advantage. TGF-alpha also induced at lactation a 6.4-fold increase in DNA synthesis in MT100 epithelial cells, many of which were binucleated. MT100 mammary tissue experienced an obvious delay in involution, resulting in the postlactational survival of a significant population of unregressed secretory epithelial cells. In contrast, another line of transgenic mice on a CD-1 genetic background (MT42), in which TGF-alpha overexpression induced liver but not mammary tumors, failed to demonstrate postlactational epithelial cell survival. These data show that TGF-alpha promotes mammary tumorigenesis in multiparous MT100 mice by stimulating secretory epithelial cell proliferation during lactation and

  18. Of Microenvironments and Mammary Stem Cells

    SciTech Connect

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

    2007-06-01

    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  19. Deoxyelephantopin, a novel multifunctional agent, suppresses mammary tumour growth and lung metastasis and doubles survival time in mice

    PubMed Central

    Huang, Chi-Chang; Lo, Chiu-Ping; Chiu, Chih-Yang; Shyur, Lie-Fen

    2010-01-01

    Background and purpose: Elephantopus scaber L. (Asteraceae) is a traditional herbal medicine with anti-cancer effects. We evaluated the in vitro and in vivo efficacy of a major sesquiterpene lactone constituent of E. scaber, deoxyelephantopin (DET), against mammary adenocarcinoma and the underlying molecular mechanism. Experimental approach: A variety of cellular assays, immunoblotting and immunohistochemistry, as well as both orthotopic and metastatic TS/A tumour models in BALB/c mice, were used. Test mice were pretreated and post-treated with DET or paclitaxel and mammary tumour growth evaluated. Key results: DET (≤2 µg·mL−1) significantly inhibited colony formation, cell proliferation, migration and invasion of TS/A cells and induced G2/M arrest and apoptosis in TS/A cells. c-Jun N-terminal kinase-mediated p21Waf1/Cip1 expression and caspase activation cascades were up-regulated by DET, effects suppressed by N-acetyl-L-cysteine. Moreover, tumour necrosis factor α-induced matrix metalloproteinase-9 enzyme activity and expression and nuclear factor-kappa B activation were abolished by DET. Pretreatment with DET was more effective than paclitaxel, for profound suppression of orthotopic tumour growth (99% vs. 68% reduction in tumour size) and lung metastasis of TS/A cells (82% vs. 63% reduction in metastatic pulmonary foci) and prolonged median survival time (56 vs. 37 days, P < 0.01) in mice. The levels of cyclooxygenase-2 and vascular endothelial growth factor in metastatic lung tissues of TS/A-bearing mice were attenuated by DET. Conclusions and implications: Our data provide evidence for the suppression of mammary adenocarcinoma by DET with several mechanisms and suggest that DET has potential as a chemopreventive agent for breast cancer. PMID:20105176

  20. MLN0264 in Previously Treated Asian Patients With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2016-06-03

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  1. The acetyltransferase Tip60 contributes to mammary tumorigenesis by modulating DNA repair

    PubMed Central

    Bassi, C; Li, Y-T; Khu, K; Mateo, F; Baniasadi, P S; Elia, A; Mason, J; Stambolic, V; Pujana, M A; Mak, T W; Gorrini, C

    2016-01-01

    The acetyltransferase Tip60/Kat5 acetylates both histone and non-histone proteins, and is involved in a variety of biological processes. By acetylating p53, Tip60 controls p53-dependent transcriptional activity and so is implicated as a tumor suppressor. However, many breast cancers with low Tip60 also show p53 mutation, implying that Tip60 has a tumor suppressor function independent of its acetylation of p53. Here, we show in a p53-null mouse model of sporadic invasive breast adenocarcinoma that heterozygosity for Tip60 deletion promotes mammary tumorigenesis. Low Tip60 reduces DNA repair in normal and tumor mammary epithelial cells, both under resting conditions and following genotoxic stress. We demonstrate that Tip60 controls homologous recombination (HR)-directed DNA repair, and that Tip60 levels correlate inversely with a gene expression signature associated with defective HR-directed DNA repair. In human breast cancer data sets, Tip60 mRNA is downregulated, with low Tip60 levels correlating with p53 mutations in basal-like breast cancers. Our findings indicate that Tip60 is a novel breast tumor suppressor gene whose loss results in genomic instability leading to cancer formation. PMID:26915295

  2. Prognosis for canine malignant mammary tumors based on TNM and histologic classification.

    PubMed

    Yamagami, T; Kobayashi, T; Takahashi, K; Sugiyama, M

    1996-11-01

    The 2-year prognosis of malignant mammary tumors seen in 175 bitches in the Tokyo metropolitan area was assessed based on their TNM clinical staging and histological classification. The larger the tumor size became (T category), the poorer was the clinical prognosis. The 2-year survival rates of the animals with regional lymph node metastasis of tumor cells (N1, N2 category) and/or distant metastasis (M1 category) were markedly lower than those of the animals without such involvement. As the grade of TNM staging increased, the prognosis was poorer, however, there were no significant differences in survival rates among subtypes of adenocarcinomas (tubular, papillary and papillary cystic) determined by WHO histological classification. It was also noticed that animals having carcinomas without tubular formation or myoepithelial cell proliferation had a lower survival rate than animals having carcinomas with those characteristics; and invasive carcinomas into adjacent skin or lymphatic/vascular vessels implied a poorer prognosis than non-invasive ones. The results suggest that a combined practice of TNM system and our evaluation on the above-mentioned 4 histologic features could be useful for prognostic determination of canine mammary cancers. PMID:8959655

  3. The acetyltransferase Tip60 contributes to mammary tumorigenesis by modulating DNA repair.

    PubMed

    Bassi, C; Li, Y-T; Khu, K; Mateo, F; Baniasadi, P S; Elia, A; Mason, J; Stambolic, V; Pujana, M A; Mak, T W; Gorrini, C

    2016-07-01

    The acetyltransferase Tip60/Kat5 acetylates both histone and non-histone proteins, and is involved in a variety of biological processes. By acetylating p53, Tip60 controls p53-dependent transcriptional activity and so is implicated as a tumor suppressor. However, many breast cancers with low Tip60 also show p53 mutation, implying that Tip60 has a tumor suppressor function independent of its acetylation of p53. Here, we show in a p53-null mouse model of sporadic invasive breast adenocarcinoma that heterozygosity for Tip60 deletion promotes mammary tumorigenesis. Low Tip60 reduces DNA repair in normal and tumor mammary epithelial cells, both under resting conditions and following genotoxic stress. We demonstrate that Tip60 controls homologous recombination (HR)-directed DNA repair, and that Tip60 levels correlate inversely with a gene expression signature associated with defective HR-directed DNA repair. In human breast cancer data sets, Tip60 mRNA is downregulated, with low Tip60 levels correlating with p53 mutations in basal-like breast cancers. Our findings indicate that Tip60 is a novel breast tumor suppressor gene whose loss results in genomic instability leading to cancer formation. PMID:26915295

  4. Do Dogs Know Bifurcations?

    ERIC Educational Resources Information Center

    Minton, Roland; Pennings, Timothy J.

    2007-01-01

    When a dog (in this case, Tim Pennings' dog Elvis) is in the water and a ball is thrown downshore, it must choose to swim directly to the ball or first swim to shore. The mathematical analysis of this problem leads to the computation of bifurcation points at which the optimal strategy changes.

  5. Stromal Effects on Mammary Gland Development and Breast Cancer

    NASA Astrophysics Data System (ADS)

    Wiseman, Bryony S.; Werb, Zena

    2002-05-01

    Breast cancer manifests itself in the mammary epithelium, yet there is a growing recognition that mammary stromal cells also play an important role in tumorigenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer, and many of the stromal factors necessary for mammary development also promote or protect against breast cancer. Here we review our present knowledge of the specific factors and cell types that contribute to epithelial-stromal crosstalk during mammary development. To find cures for diseases like breast cancer that rely on epithelial-stromal crosstalk, we must understand how these different cell types communicate with each other.

  6. Expression of glutathione, glutathione peroxidase and glutathione S-transferase pi in canine mammary tumors

    PubMed Central

    2014-01-01

    Background Glutathione (GSH) is one of the most important agents of the antioxidant defense system of the cell because, in conjunction with the enzymes glutathione peroxidase (GSH-Px) and glutathione S transferase pi (GSTpi), it plays a central role in the detoxification and biotransformation of chemotherapeutic drugs. This study evaluated the expression of GSH and the GSH-Px and GSTpi enzymes by immunohistochemistry in 30 canine mammary tumors, relating the clinicopathological parameters, clinical outcome and survival of the bitches. In an in vitro study, the expression of the genes glutamate cysteine ligase (GCLC) and glutathione synthetase (GSS) that synthesize GSH and GSH-Px gene were verified by qPCR and subjected to treatment with doxorubicin, to check the resistance of cancer cells to chemotherapy. Results The immunohistochemical expression of GSH, GSH-Px and GSTpi was compared with the clinical and pathological characteristics and the clinical outcome in the bitches, including metastasis and death. The results showed that high immunoexpression of GSH was correlated to the absence of tumor ulceration and was present in dogs without metastasis (P < 0.05). There was significant correlation of survival with the increase of GSH (P < 0.05). The expression of the GSH-Px and GSTpi enzymes showed no statistically significant correlation with the analyzed variables (p > 0.05). The analysis of the relative expression of genes responsible for the synthesis of GSH (GCLC and GSS) and GSH-Px by quantitative PCR was done with cultured cells of 10 tumor fragments from dogs with mammary tumors. The culture cells showed a decrease in GCLC and GSS expression when compared with no treated cells (P < 0.05). High GSH immunoexpression was associated with better clinical outcomes. Conclusion Therefore, high expression of the GSH seems to play an important role in the clinical outcome of patients with mammary tumors and suggest its use as prognostic marker. The in

  7. The dog genome.

    PubMed

    Galibert, F; André, C

    2006-01-01

    Over the last few centuries, several hundred dog breeds have been artificially selected through intense breeding, resulting in the modern dog population having the widest polymorphism spectrum in terms of body shape, behavior and aptitude among mammals. Unfortunately, this diversification has predisposed most breeds to specific diseases of genetic origin. The highly fragmented nature of the dog population offers a great opportunity to track the genes and alleles responsible for these diseases as well as for the various phenotypic traits. This has led to a thorough analysis of the dog genome. Here, we report the main results obtained during the last ten years, culminating in the recent publication of a complete dog genome sequence. PMID:18753768

  8. The Mammary Gland Microenvironment Directs Progenitor Cell Fate In Vivo

    PubMed Central

    Bussard, Karen M.; Smith, Gilbert H.

    2011-01-01

    The mammary gland is a unique organ that continually undergoes postnatal developmental changes. In mice, the mammary gland is formed via signals from terminal end buds, which direct ductal growth and elongation. Intriguingly, it is likely that the entire cellular repertoire of the mammary gland is formed from a single antecedent cell. Furthermore, in order to produce progeny of varied lineages (e.g., luminal and myoepithelial cells), signals from the local tissue microenvironment influence mammary stem/progenitor cell fate. Data have shown that cells from the mammary gland microenvironment reprogram adult somatic cells from other organs (testes, nerve) into cells that produce milk and express mammary epithelial cell proteins. Similar results were found for human tumorigenic epithelial carcinoma cells. Presently, it is unclear how the deterministic power of the mammary gland microenvironment controls epithelial cell fate. Regardless, signals generated by the microenvironment have a profound influence on progenitor cell differentiation in vivo. PMID:21647291

  9. Inhibition of mammary tumor promotion by dietary D,L-2-difluoromethylornithine in combination with omega-3 and omega-6 fatty acids

    SciTech Connect

    Bunce, O.R.; Abou-El-Ela, S.H. )

    1990-02-26

    The authors laboratory has shown an inhibitor effect on mammary tumor promotion by a 20% corn oil diet when D,L-2-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), was fed to female rats with 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. Analyses of mammary adenocarcinomas from these rats showed that DFMO not only inhibited ODC but also eicosanoid synthesis. Inhibition of tumor promotion, ODC activity and eicosanoid synthesis was additive when dietary combinations of DFMO and menhaden oil were fed. However, when 0.5% DFMO was fed along with 20% dietary fat, signs of toxicity were seen. The overall objective of this study was to establish the minimal and non-toxic dose of DFMO which can give an additive or synergistic antipromoter effect when fed along with dietary n-3 and/or n-6 fatty acids to female Sprague-Dawley rats with DMBA-induced mammary tumors. Four dietary levels of DFMO (0, 0.125, 0.250, and 0.500%) were fed in diets containing 20% fat as either corn, black currant seed or menhaden oil. Dose response effects on tumorigenicity as well as toxicity were noted. Long chain n-3 fatty acids gave greater inhibition of tumorigenesis than shorter chain fatty acids when combined with DFMO. DFMO (0.25%) inhibited tumorigenesis without toxic effects on weight gain, whereas, 0.125% DFMO did not alter tumorigenesis. Supporting biochemical data are presented.

  10. Dietary genistein stimulates mammary development in gilts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The possible role of the phytoestrogen, genistein, on prepubertal development of mammary glands, hormonal status and bone resorption was investigated in gilts. Forty-five gilts were fed a control diet containing soya (CTLS, n = 15), a control diet without soya (CTL0, n = 15) or the CTLS diet supplem...

  11. Contraceptive steroid toxicology in the Beagle dog and its relevance to human carcinogenicity.

    PubMed

    Owen, L N; Briggs, M H

    1976-01-01

    Problems associated with the use of the Beagle dog in chronic toxicological studies of contraceptive steroids are described. A short review is presented on the occurrence of spontaneous tumours in dogs and in bitches of various breeds. The current status of knowledge of canine reproductive hormones and endocrinology is outlined, together with effects of contraceptive steroids. The pathology and histological classification of spontaneous and induced mammary neoplasia in the dog is discussed and compared with breast cancer in women. A series of recommendations are included for future research in this field which it is hoped may resolve some of the outstanding issues and lead to a more suitable toxicological model for contraceptive steroids. PMID:64332

  12. Prognostic and predictive markers in pancreatic adenocarcinoma.

    PubMed

    Le, Nha; Sund, Malin; Vinci, Alessio

    2016-03-01

    Pancreatic ductal adenocarcinoma is characterized by a poor prognosis and a low median survival, despite improvements observed for many other solid tumours. Intensive research efforts have been undertaken during the last decades to discover new prognostic and treatment predictive biomarkers for pancreatic ductal adenocarcinoma. The mainstay of medical treatment for the disease has been the well-tolerated nucleoside analogue, gemcitabine. The only targeted agent currently used in pancreatic ductal adenocarcinoma patients is the epithelial growth factor receptor inhibitor erlotinib in combination with gemcitabine. Recently, treatment regimens such as a combination of fluorouracil-leucovorin-irinotecan-oxaliplatin (FOLFIRINOX) and the combination of nab-paclitaxel with gemcitabine have been introduced for metastatic pancreatic ductal adenocarcinoma. Although these treatment regimens significantly improve survival of patients, there are no good predictive biomarkers available that can be used to identify who would benefit most from them. Therefore, the search for predictive biomarkers that would facilitate personalization of chemotherapy is highly relevant. PMID:26769569

  13. Catumaxomab for Treatment of Peritoneal Carcinomatosis in Patients With Gastric Adenocarcinomas

    ClinicalTrials.gov

    2016-06-15

    Gastric Adenocarcinoma With Peritoneal Carcinomatosis; Siewert Type II Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis; Siewert Type III Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis

  14. BigDog

    NASA Astrophysics Data System (ADS)

    Playter, R.; Buehler, M.; Raibert, M.

    2006-05-01

    BigDog's goal is to be the world's most advanced quadruped robot for outdoor applications. BigDog is aimed at the mission of a mechanical mule - a category with few competitors to date: power autonomous quadrupeds capable of carrying significant payloads, operating outdoors, with static and dynamic mobility, and fully integrated sensing. BigDog is about 1 m tall, 1 m long and 0.3 m wide, and weighs about 90 kg. BigDog has demonstrated walking and trotting gaits, as well as standing up and sitting down. Since its creation in the fall of 2004, BigDog has logged tens of hours of walking, climbing and running time. It has walked up and down 25 & 35 degree inclines and trotted at speeds up to 1.8 m/s. BigDog has walked at 0.7 m/s over loose rock beds and carried over 50 kg of payload. We are currently working to expand BigDog's rough terrain mobility through the creation of robust locomotion strategies and terrain sensing capabilities.

  15. High corn oil and high extra virgin olive oil diets have different effects on the expression of differentiation-related genes in experimental mammary tumors.

    PubMed

    Moral, Raquel; Solanas, Montserrat; Garcia, Gemma; Grau, Laura; Vela, Elena; Escrich, Raquel; Escrich, Eduard

    2008-08-01

    Dietary lipids can modify the clinical behavior and morphological features of experimental breast tumors. We previously demonstrated that a high corn oil diet has a tumor-enhancing effect in 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced rat mammary adenocarcinomas, whereas a high olive oil diet acts as a negative modulator of carcinogenesis. In this study, we investigated whether these high fat diets modulate the expression of genes related to differentiation. Rats were induced with DMBA and fed a low fat diet, a high corn oil diet, a high olive oil diet, or both high fat diets. The expression levels of the mammary differentiation biomarkers alpha-casein, beta-casein and transferrin and of beta-actin and its transporter zipcode binding protein 1 (ZBP1) were analyzed by Northern and/or Western blot in the mammary adenocarcinomas. The high fat diets did not induce changes in the expression of caseins, while transferrin expression was increased as a result of the high olive oil diet. beta-actin mRNA levels were higher in the high fat diet groups, though no changes in the protein levels were observed. The expression of ZBP1, a protein reported as having a role in carcinogenesis, was significantly increased by the high corn oil diet. These results suggest that in this model caseins are not good biomarkers of the changes in tumor morphological differentiation conferred by the high fat diets. The modulation of transferrin and ZBP1 expression by the high olive oil and the high corn oil diets could be one of the mechanisms by which such diets have a different influence on mammary carcinogenesis. PMID:18636208

  16. [An atypical presentation of bronchial adenocarcinoma].

    PubMed

    Langouo Fontsa, M; Cstoth, I; Berghmans, T; Feoli, F; Meert, A-P

    2013-01-01

    Currently, adenocarcinoma represents 41 % of primary lung cancers in women and 34 % in men. Thyroid metastases of lung cancer are rare and usually asymptomatic. We report the case of a patient presenting with stridor secondary to an enlarged multiple nodular thyroid accompanied by cervical lymphadenopathies accompanied by an enlarged and multiple nodular thyroid and by stridor. The final diagnosis was thyroid metastases of primary lung adenocarcinoma. PMID:23951859

  17. Dogs discriminate identical twins.

    PubMed

    Pinc, Ludvík; Bartoš, Luděk; Reslová, Alice; Kotrba, Radim

    2011-01-01

    Earlier studies have shown variation among experimental attempts to establish whether human monozygotic twins that are genetically identical also have identical individual scents. In none of the cases were the dogs able to distinguish all the individual scents of monozygotic twins living in the same environment if the scents were presented to them separately. Ten specially trained police German Shepherd dogs of three Czech Republic Police Regional Headquarters were used for scent identification in our study. The dogs were supposed to match scents of two monozygotic pairs (5 and 7 years old) and two dizygotic twin pairs (8 and 13 years old). Scents were collected on cotton squares stored in glass jars. Dog handlers were blind to the experiment details. In each trial (line-up), one scent was used as a starting scent and the dog was then sent to determine if any of the 7 presented glass jars contained a matching scent. Scents of children of similar ages were used as distractors. In the matching procedure, the dogs matched correctly the scent of one twin with the other, as well as two scents collected from every single identical and non-identical twin to prove their efficacy and likewise, the presence of the matching twin scent in any given glass jar. All dogs in all trials distinguished correctly the scents of identical as well as non-identical twins. All dogs similarly matched positively two scents collected from the same individuals. Our findings indicated that specially trained German Shepherd dogs are able to distinguish individual scents of identical twins despite the fact that they live in the same environment, eat the same food and even if the scents are not presented to them simultaneously. PMID:21698282

  18. Dogs Discriminate Identical Twins

    PubMed Central

    Pinc, Ludvík; Bartoš, Luděk; Reslová, Alice; Kotrba, Radim

    2011-01-01

    Earlier studies have shown variation among experimental attempts to establish whether human monozygotic twins that are genetically identical also have identical individual scents. In none of the cases were the dogs able to distinguish all the individual scents of monozygotic twins living in the same environment if the scents were presented to them separately. Ten specially trained police German Shepherd dogs of three Czech Republic Police Regional Headquarters were used for scent identification in our study. The dogs were supposed to match scents of two monozygotic pairs (5 and 7 years old) and two dizygotic twin pairs (8 and 13 years old). Scents were collected on cotton squares stored in glass jars. Dog handlers were blind to the experiment details. In each trial (line-up), one scent was used as a starting scent and the dog was then sent to determine if any of the 7 presented glass jars contained a matching scent. Scents of children of similar ages were used as distractors. In the matching procedure, the dogs matched correctly the scent of one twin with the other, as well as two scents collected from every single identical and non-identical twin to prove their efficacy and likewise, the presence of the matching twin scent in any given glass jar. All dogs in all trials distinguished correctly the scents of identical as well as non-identical twins. All dogs similarly matched positively two scents collected from the same individuals. Our findings indicated that specially trained German Shepherd dogs are able to distinguish individual scents of identical twins despite the fact that they live in the same environment, eat the same food and even if the scents are not presented to them simultaneously. PMID:21698282

  19. A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

    PubMed Central

    2011-01-01

    Background Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. Methods We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. Results TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Conclusion Using the first

  20. pRb Inactivation in Mammary Cells Reveals Common Mechanisms for Tumor Initiation and Progression in Divergent Epithelia

    PubMed Central

    2004-01-01

    Retinoblastoma 1 (pRb) and the related pocket proteins, retinoblastoma-like 1 (p107) and retinoblastoma-like 2 (p130) (pRbf, collectively), play a pivotal role in regulating eukaryotic cell cycle progression, apoptosis, and terminal differentiation. While aberrations in the pRb-signaling pathway are common in human cancers, the consequence of pRbf loss in the mammary gland has not been directly assayed in vivo. We reported previously that inactivating these critical cell cycle regulators in divergent cell types, either brain epithelium or astrocytes, abrogates the cell cycle restriction point, leading to increased cell proliferation and apoptosis, and predisposing to cancer. Here we report that mouse mammary epithelium is similar in its requirements for pRbf function; Rbf inactivation by T121, a fragment of SV40 T antigen that binds to and inactivates pRbf proteins, increases proliferation and apoptosis. Mammary adenocarcinomas form within 16 mo. Most apoptosis is regulated by p53, which has no impact on proliferation, and heterozygosity for a p53 null allele significantly shortens tumor latency. Most tumors in p53 heterozygous mice undergo loss of the wild-type p53 allele. We show that the mechanism of p53 loss of heterozygosity is not simply the consequence of Chromosome 11 aneuploidy and further that chromosomal instability subsequent to p53 loss is minimal. The mechanisms for pRb and p53 tumor suppression in the epithelia of two distinct tissues, mammary gland and brain, are indistinguishable. Further, this study has produced a highly penetrant breast cancer model based on aberrations commonly observed in the human disease. PMID:14966529

  1. [Fatal dog bite injuries].

    PubMed

    Pollak, S; Mortinger, H

    1989-01-01

    In the absence of her parents, a girl of 4 months was killed by a 2-year old male Rottweiler dog belonging to the same family. The dog's front teeth left marks of individual, circular or scratch-like abrasions as well as slit-like severances of the skin, arranged in curved lines. The pattern of the skin-lesions largely correspond to the anatomy of the dog's set of teeth. No tissue defects (effects of devour) could be detected. Multiple traumatization of the trunk had led to serial rib fractures and ruptures of several organs. PMID:2818522

  2. Cholangiohepatitis in a dog.

    PubMed

    Forrester, S D; Rogers, K S; Relford, R L

    1992-06-01

    Cholangiohepatitis was diagnosed in a dog with a 4-day history of anorexia, vomiting, fever, and icterus. Additional findings included signs of depression, dehydration, hepatosplenomegaly, and abdominal discomfort. Exploratory laparotomy was performed, and specimens of liver, spleen, and bile were obtained. Histologic evaluation of liver and spleen revealed acute, suppurative cholangio-hepatitis and splenitis, respectively. Cultures of liver and bile yielded Klebsiella sp. The dog responded to rehydration and intravenous administration of chloramphenicol. Although uncommon, cholangiohepatitis should be suspected in dogs with anorexia, fever, vomiting, icterus, and signs of abdominal discomfort. Definitive diagnosis requires bacterial cultures of liver and bile. Administration of an appropriate antibiotic should resolve clinical signs. PMID:1624352

  3. Lung adenocarcinoma and human papillomavirus infection.

    PubMed

    Chen, Yen-Ching; Chen, Jen-Hau; Richard, Kradin; Chen, Pao-Yang; Christiani, David C

    2004-09-15

    Over the past three decades, the incidence of lung adenocarcinoma has increased worldwide. Most individuals with lung adenocarcinoma (especially women) are nonsmokers. Reported risk factors for the development of lung adenocarcinoma include cigarette smoking; exposure to cooking fumes, air pollution, second-hand smoke, asbestos, and radon; nutritional status; genetic susceptibility; immunologic dysfunction; tuberculosis infection; and asthma. Human papillomavirus (HPV) infection is a known risk factor for the development of squamous cell carcinoma (SCC), but it has not been thoroughly assessed as a potential risk factor for the development of pulmonary adenocarcinoma. More than 50% of people are infected with HPV during their lifetimes, either via intrauterine or postnatal infection. Recent studies involving Taiwanese patients have demonstrated a possible association between HPV infection and the risk of developing pulmonary adenocarcinoma. HPV transmission pathways have not yet been conclusively identified. The observation of certain types of HPV in association with cervical and oral SCC raises the possibility of sexual transmission of HPV from the cervix to the oral cavity, with subsequent transmission to the larynx and then to the lung. HPV infection and metaplasia in lung tissue may increase an individual's susceptibility to the tumorigenesis of pulmonary adenocarcinoma. Further epidemiologic and pathologic investigations will be necessary to establish a causal relation. PMID:15368331

  4. E-cadherin immunohistochemical expression in mammary gland neoplasms in bitches.

    PubMed

    Rodo, A; Malicka, E

    2008-01-01

    The aim of the study was to investigate E-cadherin expression in correlation with other neoplasm traits such as: histological type, the differentiation grade and proliferative activity. Material for the investigation comprised mammary gland tumours, collected from dogs, the patients of veterinary clinics, during surgical procedures and archival samples. All together 21 adenomas, 32 complex carcinomas, 35 simple carcinomas and 13 solid carcinomas were qualified for further investigation. E-cadherin expression was higher in adenomas as compared with carcinomas but lower in solid carcinomas as compared with simple and complex carcinomas. More over, the expression of E-cadherin decreased with the increase in the neoplasm malignancy and proliferative activity (value of the mitotic index and number of cells showing Ki67). The study has shown that the expression of E-cadherin can be used as a prognostic factor. PMID:18540208

  5. Jealousy in Dogs

    PubMed Central

    Harris, Christine R.; Prouvost, Caroline

    2014-01-01

    It is commonly assumed that jealousy is unique to humans, partially because of the complex cognitions often involved in this emotion. However, from a functional perspective, one might expect that an emotion that evolved to protect social bonds from interlopers might exist in other social species, particularly one as cognitively sophisticated as the dog. The current experiment adapted a paradigm from human infant studies to examine jealousy in domestic dogs. We found that dogs exhibited significantly more jealous behaviors (e.g., snapping, getting between the owner and object, pushing/touching the object/owner) when their owners displayed affectionate behaviors towards what appeared to be another dog as compared to nonsocial objects. These results lend support to the hypothesis that jealousy has some “primordial” form that exists in human infants and in at least one other social species besides humans. PMID:25054800

  6. How dogs drink water

    NASA Astrophysics Data System (ADS)

    Gart, Sean; Socha, Jake; Vlachos, Pavlos; Jung, Sunghwan

    2014-11-01

    Animals with incomplete cheeks (i.e. dogs and cats) need to move fluid against gravity into the body by means other than suction. They do this by lapping fluid with their tongue. When a dog drinks, it curls its tongue posteriorly while plunging it into the fluid and then quickly withdraws its tongue back into the mouth. During this fast retraction fluid sticks to the ventral part of the curled tongue and is drawn into the mouth due to inertia. We show several variations of this drinking behavior among many dog breeds, specifically, the relationship between tongue dynamics and geometry, lapping frequency, and dog weight. We also compare the results with the physical experiment of a rounded rod impact onto a fluid surface. Supported by NSF PoLS #1205642.

  7. Mimics of pancreatic ductal adenocarcinoma

    PubMed Central

    Kaza, Ravi K.; Azar, Shadi F.; Ruma, Julie A.; Francis, Isaac R.

    2013-01-01

    Abstract Several uncommon primary pancreatic tumors, inflammatory conditions, metastasis to the pancreas and peripancreatic masses can mimic the appearance of pancreatic ductal adenocarcinoma (PDA). Differentiation between these lesions and PDA can be challenging, due to the overlap in imaging features; however, familiarity with their typical imaging features and clinical presentation may be helpful in their differentiation, as in some cases, invasive diagnostic tests or unnecessary surgery can be avoided. The different pathologies that can mimic PDA include inflammatory conditions such as the various forms of pancreatitis (chronic-focal mass-forming, autoimmune and groove pancreatitis), pancreatic neuroendocrine tumors, solid pseudopapillary tumors, metastasis (solid non-lymphomatous and hematologic), congenital variants (annular pancreas), as well as peripancreatic lesions (accessory spleen, adrenal masses, duodenal masses, lymph nodes and vascular lesions), and certain rare pancreatic tumors (e.g., acinar cell tumors, solid serous tumors, hamartoma and solitary fibrous tumors). The clinical presentation and imaging features of the most commonly encountered mimics of PDA are discussed in this presentation with representative illustrations. PMID:24060833

  8. The mammary gland-specific marsupial ELP and eutherian CTI share a common ancestral gene

    PubMed Central

    2012-01-01

    Background The marsupial early lactation protein (ELP) gene is expressed in the mammary gland and the protein is secreted into milk during early lactation (Phase 2A). Mature ELP shares approximately 55.4% similarity with the colostrum-specific bovine colostrum trypsin inhibitor (CTI) protein. Although ELP and CTI both have a single bovine pancreatic trypsin inhibitor (BPTI)-Kunitz domain and are secreted only during the early lactation phases, their evolutionary history is yet to be investigated. Results Tammar ELP was isolated from a genomic library and the fat-tailed dunnart and Southern koala ELP genes cloned from genomic DNA. The tammar ELP gene was expressed only in the mammary gland during late pregnancy (Phase 1) and early lactation (Phase 2A). The opossum and fat-tailed dunnart ELP and cow CTI transcripts were cloned from RNA isolated from the mammary gland and dog CTI from cells in colostrum. The putative mature ELP and CTI peptides shared 44.6%-62.2% similarity. In silico analyses identified the ELP and CTI genes in the other species examined and provided compelling evidence that they evolved from a common ancestral gene. In addition, whilst the eutherian CTI gene was conserved in the Laurasiatherian orders Carnivora and Cetartiodactyla, it had become a pseudogene in others. These data suggest that bovine CTI may be the ancestral gene of the Artiodactyla-specific, rapidly evolving chromosome 13 pancreatic trypsin inhibitor (PTI), spleen trypsin inhibitor (STI) and the five placenta-specific trophoblast Kunitz domain protein (TKDP1-5) genes. Conclusions Marsupial ELP and eutherian CTI evolved from an ancestral therian mammal gene before the divergence of marsupials and eutherians between 130 and 160 million years ago. The retention of the ELP gene in marsupials suggests that this early lactation-specific milk protein may have an important role in the immunologically naïve young of these species. PMID:22681678

  9. Hybrid vigour in dogs?

    PubMed

    Nicholas, Frank W; Arnott, Elizabeth R; McGreevy, Paul D

    2016-08-01

    Evidence from other species justifies the hypotheses that useful hybrid vigour occurs in dogs and that it can be exploited for improved health, welfare and fitness for purpose. Unfortunately, most of the relevant published canine studies do not provide estimates of actual hybrid vigour because of inadequate specification of the parentage of mixed-bred dogs. To our knowledge, only three published studies have shed any light on actual hybrid vigour in dogs. There are two reports of actual hybrid vigour between Labrador and Golden retrievers, the first ranging from +2.5% to -6.0% for components of a standardised applied-stimulus behavioural test, and the second being at least +12.4% for chance of graduating as a guide dog. The third study provides a minimum estimate of negative actual hybrid vigour: crossbreds between Labrador retrievers and poodles had a higher prevalence of multifocal retinal dysplasia than the average prevalence in their purebred parent breeds. The lack of estimates of actual hybrid vigour can be overcome by including the exact nature of the cross (e.g. F1, F2 or backcross) and their purebred parental breeds in the specification of mixed-bred dogs. Even if only F1 crossbreds can be categorised, this change would enable researchers to conduct substantial investigations to determine whether hybrid vigour has any utility for dog breeding. PMID:27387730

  10. Genome aberrations in canine mammary carcinomas and their detection in cell-free plasma DNA.

    PubMed

    Beck, Julia; Hennecke, Silvia; Bornemann-Kolatzki, Kirsten; Urnovitz, Howard B; Neumann, Stephan; Ströbel, Philipp; Kaup, Franz-Josef; Brenig, Bertram; Schütz, Ekkehard

    2013-01-01

    Mammary tumors are the most frequent cancers in female dogs exhibiting a variety of histopathological differences. There is lack of knowledge about the genomes of these common dog tumors. Five tumors of three different histological subtypes were evaluated. Massive parallel sequencing (MPS) was performed in comparison to the respective somatic genome of each animal. Copy number and structural aberrations were validated using droplet digital PCR (ddPCR). Using mate-pair sequencing chromosomal aneuploidies were found in two tumors, frequent smaller deletions were found in one, inter-chromosomal fusions in one other, whereas one tumor was almost normal. These aberrations affect several known cancer associated genes such as cMYC, and KIT. One common deletion of the proximal end of CFA27, harboring the tumor suppressor gene PFDN5 was detected in four tumors. Using ddPCR, this deletion was validated and detected in 50% of tumors (N = 20). Breakpoint specific dPCRs were established for four tumors and tumor specific cell-free DNA (cfDNA) was detected in the plasma. In one animal tumor-specific cfDNA was found >1 year after surgery, attributable to a lung metastasis. Paired-end sequencing proved that copy-number imbalances of the tumor are reflected by the cfDNA. This report on chromosomal instability of canine mammary cancers reveals similarities to human breast cancers as well as special canine alterations. This animal model provides a framework for using MPS for screening for individual cancer biomarkers with cost effective confirmation and monitoring using ddPCR. The possibility exists that ddPCR can be expanded to screening for common cancer related variants. PMID:24098698

  11. Genome Aberrations in Canine Mammary Carcinomas and Their Detection in Cell-Free Plasma DNA

    PubMed Central

    Beck, Julia; Hennecke, Silvia; Bornemann-Kolatzki, Kirsten; Urnovitz, Howard B.; Neumann, Stephan; Ströbel, Philipp; Kaup, Franz-Josef; Brenig, Bertram; Schütz, Ekkehard

    2013-01-01

    Mammary tumors are the most frequent cancers in female dogs exhibiting a variety of histopathological differences. There is lack of knowledge about the genomes of these common dog tumors. Five tumors of three different histological subtypes were evaluated. Massive parallel sequencing (MPS) was performed in comparison to the respective somatic genome of each animal. Copy number and structural aberrations were validated using droplet digital PCR (ddPCR). Using mate-pair sequencing chromosomal aneuploidies were found in two tumors, frequent smaller deletions were found in one, inter-chromosomal fusions in one other, whereas one tumor was almost normal. These aberrations affect several known cancer associated genes such as cMYC, and KIT. One common deletion of the proximal end of CFA27, harboring the tumor suppressor gene PFDN5 was detected in four tumors. Using ddPCR, this deletion was validated and detected in 50% of tumors (N = 20). Breakpoint specific dPCRs were established for four tumors and tumor specific cell-free DNA (cfDNA) was detected in the plasma. In one animal tumor-specific cfDNA was found >1 year after surgery, attributable to a lung metastasis. Paired-end sequencing proved that copy-number imbalances of the tumor are reflected by the cfDNA. This report on chromosomal instability of canine mammary cancers reveals similarities to human breast cancers as well as special canine alterations. This animal model provides a framework for using MPS for screening for individual cancer biomarkers with cost effective confirmation and monitoring using ddPCR. The possibility exists that ddPCR can be expanded to screening for common cancer related variants. PMID:24098698

  12. Establishment and characterization of a new cell line of canine inflammatory mammary cancer: IPC-366.

    PubMed

    Caceres, Sara; Peña, Laura; de Andres, Paloma J; Illera, Maria J; Lopez, Mirtha S; Woodward, Wendy A; Reuben, James M; Illera, Juan C

    2015-01-01

    Canine inflammatory mammary cancer (IMC) shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as a natural model for human inflammatory breast cancer (IBC). The aim of this study was to characterize a new cell line from IMC (IPC-366) for the comparative study of both IMC and IBC. Tumors cells from a female dog with clinical IMC were collected. The cells were grown under adherent conditions. The growth, cytological, ultrastructural and immunohistochemical (IHC) characteristics of IPC-366 were evaluated. Ten female Balb/SCID mice were inoculated with IPC-366 cells to assess their tumorigenicity and metastatic potential. Chromosome aberration test and Karyotype revealed the presence of structural aberration, numerical and neutral rearrangements, demonstrating a chromosomal instability. Microscopic examination of tumor revealed an epithelial morphology with marked anysocytosis. Cytological and histological examination of smears and ultrathin sections by electron microscopy revealed that IPC-366 is formed by highly malignant large round or polygonal cells characterized by marked atypia and prominent nucleoli and frequent multinucleated cells. Some cells had cytoplasmic empty spaces covered by cytoplasmic membrane resembling capillary endothelial cells, a phenomenon that has been related to s vasculogenic mimicry. IHC characterization of IPC-366 was basal-like: epithelial cells (AE1/AE3+, CK14+, vimentin+, actin-, p63-, ER-, PR-, HER-2, E-cadherin, overexpressed COX-2 and high Ki-67 proliferation index (87.15 %). At 2 weeks after inoculating the IPC-366 cells, a tumor mass was found in 100 % of mice. At 4 weeks metastases in lung and lymph nodes were found. Xenograph tumors maintained the original IHC characteristics of the female dog tumor. In summary, the cell line IPC-366 is a fast growing malignant triple negative cell line model of inflammatory mammary carcinoma that can be used for the comparative

  13. Establishment and Characterization of a New Cell Line of Canine Inflammatory Mammary Cancer: IPC-366

    PubMed Central

    Caceres, Sara; Peña, Laura; de Andres, Paloma J.; Illera, Maria J.; Lopez, Mirtha S.; Woodward, Wendy A.; Reuben, James M.; Illera, Juan C.

    2015-01-01

    Canine inflammatory mammary cancer (IMC) shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as a natural model for human inflammatory breast cancer (IBC). The aim of this study was to characterize a new cell line from IMC (IPC-366) for the comparative study of both IMC and IBC. Tumors cells from a female dog with clinical IMC were collected. The cells were grown under adherent conditions. The growth, cytological, ultrastructural and immunohistochemical (IHC) characteristics of IPC-366 were evaluated. Ten female Balb/SCID mice were inoculated with IPC-366 cells to assess their tumorigenicity and metastatic potential. Chromosome aberration test and Karyotype revealed the presence of structural aberration, numerical and neutral rearrangements, demonstrating a chromosomal instability. Microscopic examination of tumor revealed an epithelial morphology with marked anysocytosis. Cytological and histological examination of smears and ultrathin sections by electron microscopy revealed that IPC-366 is formed by highly malignant large round or polygonal cells characterized by marked atypia and prominent nucleoli and frequent multinucleated cells. Some cells had cytoplasmic empty spaces covered by cytoplasmic membrane resembling capillary endothelial cells, a phenomenon that has been related to s vasculogenic mimicry. IHC characterization of IPC-366 was basal-like: epithelial cells (AE1/AE3+, CK14+, vimentin+, actin-, p63-, ER-, PR-, HER-2, E-cadherin, overexpressed COX-2 and high Ki-67 proliferation index (87.15 %). At 2 weeks after inoculating the IPC-366 cells, a tumor mass was found in 100 % of mice. At 4 weeks metastases in lung and lymph nodes were found. Xenograph tumors maintained the original IHC characteristics of the female dog tumor. In summary, the cell line IPC-366 is a fast growing malignant triple negative cell line model of inflammatory mammary carcinoma that can be used for the comparative

  14. VEGFR-2 expression in malignant tumours of the canine mammary gland: a prospective survival study.

    PubMed

    Santos, A; Lopes, C; Gärtner, F; Matos, A J F

    2016-09-01

    Vascular endothelial growth factor receptor-2 (VEGFR-2) is the main receptor activated by vascular endothelial growth factor -A (VEGF-A) to promote tumour angiogenesis. Its clinical prognostic value has not been studied in canine mammary tumours (CMTs). Dogs with mammary cancer were enrolled in a survival study and the immunohistochemical expressions of VEGFR-2 and VEGF-A were analysed and associated with clinicopathological features. VEGFR-2 expression was associated with VEGF immunoreactivity in cancer cells, supporting the presence of an autocrine loop that may be involved in CMTs growth and survival. VEGFR-2 was also expressed by endothelial cells from tumour vasculature and positively associated with stromal matrix metalloproteinase-9 (MMP-9), suggesting the existence of a link between endothelial cells activation and up-regulation of matrix degrading proteins. Carcinosarcomas exhibited high VEGFR-2 expression suggesting that it may be one of the activated molecular pathways in this aggressive histological type and that VEGFR-2 inhibitors may constitute a potential treatment to improve the prognosis of these patients. Both VEGF and VEGFR-2 immunoreactivities were independent of patients' overall survival (OS) and disease-free survival (DFS). PMID:24976305

  15. Significance of caveolin-1 and matrix metalloproteinase 14 gene expression in canine mammary tumours.

    PubMed

    Ebisawa, M; Iwano, H; Nishikawa, M; Tochigi, Y; Komatsu, T; Endou, Y; Hirayama, K; Taniyama, H; Kadosawa, T; Yokota, H

    2015-11-01

    Canine mammary tumours (CMTs) are the most common neoplasms affecting female dogs. There is an urgent need for molecular biomarkers that can detect early stages of the disease in order to improve accuracy of CMT diagnosis. The aim of this study was to examine whether caveolin-1 (Cav-1) and matrix metalloproteinase 14 (MMP14) are associated with CMT histological malignancy and invasion. Sixty-five benign and malignant CMT samples and six normal canine mammary glands were analysed using quantitative reverse transcription-polymerase chain reaction. Cav-1 and MMP14 genes were highly expressed in CMT tissues compared to normal tissues. Cav-1 especially was overexpressed in malignant and invasive CMT tissues. When a CMT cell line was cultured on fluorescent gelatin-coated coverslips, localisation of Cav-1 was observed at invadopodia-mediated degradation sites of the gelatin matrix. These findings suggest that Cav-1 may be involved in CMT invasion and that the markers may be useful for estimating CMT malignancy. PMID:26364240

  16. Serum and intratumoural GH and IGF-I concentrations: prognostic factors in the outcome of canine mammary cancer.

    PubMed

    Queiroga, Felisbina L; Pérez-Alenza, Dolores; Silvan, Gema; Peña, Laura; Lopes, Carlos S; Illera, Juan C

    2010-12-01

    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. PMID:20381105

  17. The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development

    NASA Astrophysics Data System (ADS)

    Finke, Daniela; Luther, Sanjiv A.; Acha-Orbea, Hans

    2003-01-01

    Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers and a lifelong neutralizing Ab response. We show that removal of the draining lymph node after establishment of the germinal center reaction led to complete loss of neutralizing Abs despite comparable infection levels in peripheral lymphocytes. Importantly, in the absence of neutralization, only the exocrine organs mammary gland, salivary gland, pancreas, and skin showed strikingly increased infection, resulting in accelerated mammary tumor development. Induction of stronger neutralization did not influence chronic infection levels of peripheral lymphoid organs but strongly inhibited mammary gland infection and virus transmission to the next generation. Taken together, we provide evidence that a tight equilibrium in virus neutralization allows limited infection of exocrine organs and controls cancer development in susceptible mouse strains. These experiments show that a strong neutralizing Ab response induced after infection is not able to control lymphoid MMTV infection. Strong neutralization, however, is capable of blocking amplification of mammary gland infection, tumor development, and virus transmission to the next generation. The results also indicate a role of neutralization in natural resistance to MMTV infection.

  18. Irinotecan, Cisplatin, and Bevacizumab in Treating Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

    ClinicalTrials.gov

    2013-06-03

    Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

  19. Radiologic and histologic presentation of male mammary myofibroblastoma.

    PubMed

    Omar, Lena A; Rojanapremsuk, Theera; Saluja, Karan; Merchant, Kanwal A; Sharma, Pooja B

    2016-07-01

    Mammary myofibroblastoma is a rare mesenchymal neoplasm that typically presents in older men and women. Less commonly, these benign tumors may also occur in soft tissues located outside of the breast, in which case they are referred to as mammary-type myofibroblastomas. The histologic composition of this benign spindle cell tumor can be markedly varied. We present a case of a large mammary myofibroblastoma in a male patient and discuss the typical imaging and histologic makeup of these tumors. PMID:27365886

  20. Radiologic and histologic presentation of male mammary myofibroblastoma

    PubMed Central

    Rojanapremsuk, Theera; Saluja, Karan; Merchant, Kanwal A.; Sharma, Pooja B.

    2016-01-01

    Mammary myofibroblastoma is a rare mesenchymal neoplasm that typically presents in older men and women. Less commonly, these benign tumors may also occur in soft tissues located outside of the breast, in which case they are referred to as mammary-type myofibroblastomas. The histologic composition of this benign spindle cell tumor can be markedly varied. We present a case of a large mammary myofibroblastoma in a male patient and discuss the typical imaging and histologic makeup of these tumors. PMID:27365886

  1. Atherosclerosis and the internal mammary arteries

    SciTech Connect

    Singh, R.N.

    1983-06-01

    One hundred and fifty patients with coronary artery disease (CAD), 14 (9.3%) of whom had coexisting peripheral vascular disease, underwent bilateral internal mammary arteriography to study the incidence and extent of atherosclerosis in these vessels. Significant atherosclerosis of the internal mammary arteries (IMAs) was present in three patients (2%), of whom one had coexisting peripheral vascular disease. Lesions in the IMAs were found either proximally, close to the origin or distally, around the terminal bifurcation. Six of the 14 patients with peripheral vascular disease (4% of total subjects) had significant atherosclerosis of the brachiocephalic arteries. Atherosclerotic involvement of the IMA is very unusual and rarely interferes with the use of these vessels for coronary bypass. More common, however, is atherosclerosis of the subclavian arteries, a contraindication for IMA grafting if the lesion is proximal to the IMA origin.

  2. Adaptive Immune Regulation of Mammary Postnatal Organogenesis.

    PubMed

    Plaks, Vicki; Boldajipour, Bijan; Linnemann, Jelena R; Nguyen, Nguyen H; Kersten, Kelly; Wolf, Yochai; Casbon, Amy-Jo; Kong, Niwen; van den Bijgaart, Renske J E; Sheppard, Dean; Melton, Andrew C; Krummel, Matthew F; Werb, Zena

    2015-09-14

    Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland (MG) is the only organ developing predominantly after birth, we utilized it as a powerful system to study adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ (IFNγ)-producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses, regulating normal development, changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation. PMID:26321127

  3. Epigenetic regulation of LSD1 during mammary carcinogenesis

    PubMed Central

    Wu, Yadi; Zhou, Binhua P

    2014-01-01

    Inheritable epigenetic regulation is integral to the dynamic control of gene expression under different stimuli for cellular homeostasis and disease progression. Histone methylation is a common and important type of chromatin modification. LSD1, the first known histone lysine-specific demethylase, operates as a key component of several corepressor complexes during development and in disease states. In this review, we focus on the regulation of LSD1 in mammary carcinogenesis. LSD1 plays a role in promoting mammary tumor metastasis and proliferation and in maintaining mammary cancer stem cells. Therefore, LSD1 represents a viable therapeutic target for effective treatment of mammary carcinogenesis. PMID:27308339

  4. Save or sacrifice the internal mammary pedicle during anterior mediastinotomy?

    PubMed

    Apostolakis, Efstratios; Papakonstantinou, Nikolaos A; Chlapoutakis, Serafeim; Prokakis, Christos

    2014-07-01

    Ligation and dissection of internal mammary vessels is the most under-estimated complication of anterior mediastinotomy. However, patients requiring anterior mediastinotomy may experience long survival that makes the development of ischemic heart disease throughout their life possible. Therefore, the un-judicial sacrifice of the internal mammary pedicle may deprive them from the benefit to have their internal mammary artery used as a graft in order to successfully bypass severe left anterior descending artery stenoses. We recommend the preservation of the internal mammary pedicle during anterior mediastinotomy, which should be a common message among our colleagues from the beginning of their training. PMID:24987471

  5. Foxa1 is essential for mammary duct formation.

    PubMed

    Liu, Yi; Zhao, Yongbing; Skerry, Benjamin; Wang, Xiao; Colin-Cassin, Christelle; Radisky, Derek C; Kaestner, Klaus H; Li, Zhaoyu

    2016-05-01

    The transcription factor forkhead box protein A1 (FOXA1) plays a critical role in the proliferation of human breast cancer cells, particularly estrogen receptor alpha (ERα)-positive luminal breast cancer cells. However, genetic studies of the requirement for Foxa1 in mammary tumor formation in mice have been hampered by the lack of a conditional gene ablation. We examined three mouse models of mammary-specific ablation of Foxa1 in ductal epithelial cells to identify the best system for complete and mammary-specific ablation of Foxa1. We found that MMTV-Cre and MMTV-rtTA;Tet-On-Cre led to partial deletion of Foxa1 and attenuated mammary duct formation, whereas Krt14-Cre led to complete ablation of Foxa1 and abolished mammary duct formation, in Foxa1(loxP/loxP) mice. These results demonstrate that Foxa1 is essential for mammary duct formation, and reveal a series of mouse models in which mammary expression of Foxa1 can be attenuated or completely blocked. Our study also suggests a potentially powerful model for complete ablation of Foxa1 in mammary epithelial cells using Krt14-driven Cre expression in an inducible manner, such as Krt14-rtTA;Tet-On-Cre. This model system will facilitate further in vivo functional studies of Foxa1 or other factors in mammary gland development and tumor formation and progression. genesis 54:277-285, 2016. © 2016 Wiley Periodicals, Inc. PMID:26919034

  6. A human gallbladder adenocarcinoma cell line.

    PubMed

    Johzaki, H; Iwasaki, H; Nishida, T; Isayama, T; Kikuchi, M

    1989-12-01

    A cell strain (FU-GBC-1) was established from cancerous ascites of a 68-year-old male patient with well-differentiated adenocarcinoma of the gallbladder. By light and electron microscopy, the cultured cells showed the morphologic features of adenocarcinoma characterized by gland-like structures, intracellular microcystic spaces, and mucous production. Immunoperoxidase stains showed that FU-GBC-1 cells expressed several epithelial tumor antigens including CA 19-9, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA). The cell strain has been in continuous culture up to passage 44 for 1 1/2 years, with the population doubling time of 120 hours. The cytogenetic analysis by a G-band technique showed a constant loss of chromosome Y in FU-GBC-1 cells. The modal chromosome number at passage 12 was 82 with a range of 77 to 85. Flow cytometry with an ethidium bromide technique additionally confirmed aneuploid DNA content (4C) in the cultured cells at passage 12 and 35. Inoculation of FU-GBC-1 cells into the dermis of BALB/c nude mice produced transplantable adenocarcinoma identical to the original tumor. Because no continuous cell lines of the well-differentiated type of gallbladder adenocarcinoma have been reported in the literature currently, the newly established cell strain we report may yield a useful system for studying the morphologic and biologic characteristics of gallbladder adenocarcinoma. PMID:2680052

  7. Risk factors for adenocarcinoma of the lung

    SciTech Connect

    Brownson, R.C.; Reif, J.S.; Keefe, T.J.; Ferguson, S.W.; Pritzl, J.A.

    1987-01-01

    The relation between various risk factors and adenocarcinoma of the lung was evaluated in a case-control study. Subjects were selected from the Colorado Central Cancer Registry from 1979-1982 in the Denver metropolitan area. A total of 102 (50 males and 52 females) adenocarcinoma case interviews and 131 (65 males and 66 females) control interviews were completed. The control group consisted of persons with cancers of the colon and bone marrow. The risk estimates associated with cigarette smoking were significantly elevated among males (odds ratio (OR) = 4.49) and females (OR = 3.95) and were found to increase significantly (p less than 0.01) with increasing levels of cigarette smoking for both males and females. For adenocarcinoma in females, the age- and smoking-adjusted odds ratios at different levels of passive smoke exposure followed an increasing overall trend (p = 0.05). After additional adjustment for potential confounders, prior cigarette use remained the most significant predictor of risk of adenocarcinoma among males and females. Analysis restricted to nonsmoking females revealed a risk of adenocarcinoma of 1.68 (95% confidence interval (Cl) = 0.39-2.97) for passive smoke exposure of four or more hours per day. Neither sex showed significantly elevated risk for occupational exposures, although males bordered on significance (OR = 2.23, 95% Cl = 0.97-5.12). The results suggest the need to develop cell type-specific etiologic hypotheses.

  8. Mammary stem cells: expansion and animal productivity

    PubMed Central

    2014-01-01

    Identification and characterization of mammary stem cells and progenitor cells from dairy animals is important in the understanding of mammogenesis, tissue turnover, lactation persistency and regenerative therapy. It has been realized by many investigators that altered lactation, long dry periods (non-milking period between two consecutive lactation cycles), abrupt cessation of lactation (common in water buffaloes) and disease conditions like mastitis, greatly reduce milk yield thus render huge financial losses within the dairy sector. Cellular manipulation of specialized cell types within the mammary gland, called mammary stem cells (MaSCs)/progenitor cells, might provide potential solutions to these problems and may improve milk production. In addition, MaSCs/progenitor cells could be used in regenerative therapy against tissue damage caused by mastitis. This review discusses methods of MaSC/progenitor cell manipulation and their mechanisms in bovine and caprine animals. Author believes that intervention of MaSCs/progenitor cells could lessen the huge financial losses to the dairy industry globally. PMID:25057352

  9. PKA signaling drives mammary tumorigenesis through Src.

    PubMed

    Beristain, A G; Molyneux, S D; Joshi, P A; Pomroy, N C; Di Grappa, M A; Chang, M C; Kirschner, L S; Privé, G G; Pujana, M A; Khokha, R

    2015-02-26

    Protein kinase A (PKA) hyperactivation causes hereditary endocrine neoplasias; however, its role in sporadic epithelial cancers is unknown. Here, we show that heightened PKA activity in the mammary epithelium generates tumors. Mammary-restricted biallelic ablation of Prkar1a, which encodes for the critical type-I PKA regulatory subunit, induced spontaneous breast tumors characterized by enhanced type-II PKA activity. Downstream of this, Src phosphorylation occurs at residues serine-17 and tyrosine-416 and mammary cell transformation is driven through a mechanism involving Src signaling. The phenotypic consequences of these alterations consisted of increased cell proliferation and, accordingly, expansion of both luminal and basal epithelial cell populations. In human breast cancer, low PRKAR1A/high SRC expression defines basal-like and HER2 breast tumors associated with poor clinical outcome. Together, the results of this study define a novel molecular mechanism altered in breast carcinogenesis and highlight the potential strategy of inhibiting SRC signaling in treating this cancer subtype in humans. PMID:24662820

  10. Oxytocin binding sites in bovine mammary tissue

    SciTech Connect

    Zhao, Xin.

    1989-01-01

    Oxytocin binding sites were identified and characterized in bovine mammary tissue. ({sup 3}H)-oxytocin binding reached equilibrium by 50 min at 20{degree}C and by 8 hr at 4{degree}C. The half-time of displacement at 20{degree}C was approximately 1 hr. Thyrotropin releasing hormone, adrenocorticotropin, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl-L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive. In the presence of 10 nM LiCl, addition of oxytocin to dispersed bovine mammary cells, in which phosphatidylinositol was pre-labelled, caused a time and dose-dependent increase in radioactive inositiol monophosphate incorporation. The possibility that there are distinct vasopressin receptors in bovine mammary tissue was investigated. ({sup 3}H)-vasopressin binding reached equilibrium by 40 min at 20{degree}. The half-time of displacement at 20{degree}C was approximately 1 hr. The ability of the peptides to inhibit ({sup 3}H)-vasopressin binding was: (Thr{sup 4},Gly{sup 7})-oxytocin > Arg{sup 8}-vasopressin > (lys{sup 8})-vasopressin > (Deamino{sup 1},D-arg{sup 8})-vasopressin > oxytocin > d (CH{sub 2}){sub 5}Tyr(Me)AVP.

  11. Tweak induces mammary epithelial branching morphogenesis.

    PubMed

    Michaelson, Jennifer S; Cho, Sandy; Browning, Beth; Zheng, Timothy S; Lincecum, John M; Wang, Monica Z; Hsu, Yen-Ming; Burkly, Linda C

    2005-04-14

    Members of the tumor necrosis factor (TNF) superfamily regulate cell survival and proliferation and have been implicated in cancer. Tweak (TNF-related weak inducer of apoptosis) has pleiotropic biological functions including proapoptotic, proangiogenic and proinflammatory activities. We explored a role for Tweak in mammary gland transformation using a three-dimensional model culture system. Tweak stimulates a branching morphogenic phenotype, similar to that induced by pro-oncogenic factors, in Eph4 mammary epithelial cells cultured in matrigel. Increased proliferation and invasiveness are observed, with a concomitant inhibition of functional differentiation. Levels of matrix metalloproteinase-9 (MMP-9) are significantly increased following Tweak treatment. Notably, MMP inhibitors are sufficient to block the branching phenotype induced by Tweak. The capacity to promote proliferation, inhibit differentiation and induce invasion suggests a role for Tweak in mammary gland tumorigenesis. Consistent with this, we have observed elevated protein levels of the Tweak receptor, Fn14, in human breast tumor cell lines and xenograft models as well as in primary human breast tumors. Together, our results suggest that the Tweak/Fn14 pathway may be protumorigenic in human breast cancer. PMID:15735761

  12. Dog Ownership, Dog Walking, and Children's and Parents' Physical Activity

    ERIC Educational Resources Information Center

    Salmon, Jo; Timperio, Anna; Chu, Binh; Veitch, Jenny

    2010-01-01

    This study aimed to determine cross-sectional associations of dog ownership, dog walking, and physical activity (PA) among children and their parents. Objective measures of PA were obtained for children ages 5-6 and 10-12 years from 19 primary schools across Melbourne, Australia. Parents self-reported their PA, dog ownership, and frequency of dog…

  13. Treating Cushing's Disease in Dogs

    MedlinePlus

    ... on top of the kidneys. Dogs, cats, and horses, as well as humans, can get Cushing's disease. ... commonly found in dogs than in cats or horses. "Cortisol is one of the body's natural steroids," ...

  14. Upper Airway Injury in Dogs Secondary to Trauma: 10 Dogs (2000-2011).

    PubMed

    Basdani, Eleni; Papazoglou, Lysimachos G; Patsikas, Michail N; Kazakos, Georgios M; Adamama-Moraitou, Katerina K; Tsokataridis, Ioannis

    2016-01-01

    Ten dogs that presented with trauma-induced upper airway rupture or stenosis were reviewed. Tracheal rupture was seen in seven dogs, tracheal stenosis in one dog, and laryngeal rupture in two dogs. Clinical abnormalities included respiratory distress in five dogs, subcutaneous emphysema in eight, air leakage through the cervical wound in seven, stridor in three dogs, pneumomediastinum in four and pneumothorax in one dog. Reconstruction with simple interrupted sutures was performed in four dogs, tracheal resection and end-to-end anastomosis in five dogs, and one dog was euthanized intraoperatively. Complications were seen in three dogs including aspiration pneumonia in one and vocalization alterations in two dogs. PMID:27487354

  15. Preventing aggressive behaviour in dogs.

    PubMed

    Orritt, Rachel

    2016-07-01

    Delegates from around the world met at the University of Lincoln on June 11 and 12 for the third annual UK Dog Bite Prevention and Behaviour conference. The conference, hosted by dog trainer Victoria Stilwell, brings together dog behaviour experts to discuss possible solutions to this public health issue. Rachel Orritt, who has been examining the perceptions, assessment and management of human-directed aggressive behaviour in dogs for her PhD, reports. PMID:27389748

  16. Dog saliva – an important source of dog allergens

    PubMed Central

    Polovic, N; Wadén, K; Binnmyr, J; Hamsten, C; Grönneberg, R; Palmberg, C; Milcic-Matic, N; Bergman, T; Grönlund, H; van Hage, M; Crameri, Reto

    2013-01-01

    Background Allergy to dog (Canis familiaris) is a worldwide common cause of asthma and allergic rhinitis. However, dander extract in routine diagnostics is not an optimal predictor of IgE-mediated dog allergy. Our objective was to evaluate saliva as an allergen source for improved diagnostics of allergy to dog. Methods IgE-binding proteins in dog saliva and dander extract were analysed by immunoblot and mass spectrometry (LC-MS/MS) using pooled or individual sera from dog-allergic patients (n = 13). Sera from 59 patients IgE positive to dander and 55 patients IgE negative to dander but with symptoms to dog were analysed for IgE against saliva and dander by ELISA. Basophil stimulation with dog saliva and dander extract was measured by flow cytometry among three dog-allergic patients. Additionally, IgE-binding protein profiles of saliva from different breeds were investigated by immunoblot. Results Greater number and diversity of IgE-binding proteins was found in saliva compared to dander extract and varied among dog breeds. In saliva, Can f 1, 2, 3 and 6 were identified but also four new saliva allergen candidates. The majority of the 59 dog dander–positive sera (n = 44) were IgE positive to dog saliva. Among patients IgE negative to dander, but with symptoms to dog, 20% were IgE positive to saliva. The biological activity of saliva was confirmed by basophil degranulation. Conclusions Dog saliva is an allergen source for improved diagnostics of dog allergy. The IgE-binding protein profile of saliva from different dogs varies. PMID:23464525

  17. Botulinum toxin type A as an adjunct in postoperative pain management in dogs undergoing radical mastectomy.

    PubMed

    Vilhegas, S; Cassu, R N; Barbero, R C; Crociolli, G C; Rocha, T L A; Gomes, D R

    2015-10-17

    The aim of this randomised placebo-controlled, observer-blinded study was to evaluate the analgesic effects of botulinum toxin type A (BoNT-A) as an adjunct for postoperative pain control in dogs. Sixteen dogs undergoing bilateral radical mastectomy for treatment of mammary tumours were enrolled. Twenty-four hours before surgery, the subjects were distributed into two groups of eight dogs each: 7 iu/kg BoNT-A (BoNT-A) or saline (Control) was administered subcutaneously in each mammary gland. Following sedation with intramuscular 0.03 mg/kg acepromazine and 0.3 mg/kg morphine, anaesthesia was induced intravenously with 4 mg/kg propofol and maintained with isoflurane/O2. Postoperative analgesia was evaluated for 72 hours after extubation using the Visual Analogue Scale (VAS) and modified Glasgow Composite Measure Pain Scale (modified-GCMPS). Rescue analgesia was provided with intramuscular morphine (0.5 mg/kg). Data were analysed using analysis of variance, Tukey's test, Mann-Whitney U test and Friedman test (P<0.05). The pain scores were significantly lower in the BoNT-A than in the Control from 8 hours to 60 hours and from 12 hours to 60 hours after extubation, based on the VAS and modified-GCMPS, respectively. Rescue analgesia was required by significantly more dogs in the Control (7/8) compared with the BoNT-A (2/8) (P=0.022). Pre-emptive BoNT-A appears to be effective as an adjuvant for postoperative pain management in dogs undergoing bilateral radical mastectomy. PMID:26446882

  18. 76 FR 35162 - Service Dogs

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... AFFAIRS 38 CFR Part 17 RIN 2900-AN51 Service Dogs AGENCY: Department of Veterans Affairs. ACTION: Proposed... veterans in need of service dogs. Under current regulations, VA provides benefits to veterans with guide dogs, and this rulemaking would broaden and clarify those benefits. This rulemaking would...

  19. A Subset of Sinonasal Non-Intestinal Type Adenocarcinomas are Truly Seromucinous Adenocarcinomas: A Morphologic and Immunophenotypic Assessment and Description of a Novel Pitfall.

    PubMed

    Purgina, Bibianna; Bastaki, Jassem M; Duvvuri, Umamaheswar; Seethala, Raja R

    2015-12-01

    While sinonasal intestinal type adenocarcinoma (ITAC) is defined by an intestinal phenotype, non-intestinal type adenocarcinoma (non-ITAC) is traditionally viewed as a diagnosis of exclusion, despite previous implication of a seromucinous phenotype and similarity to sinonasal seromucinous hamartomas (SSH). We performed a comparison of clinicopathologic and immunophenotypic features of ITAC, non-ITAC and SSH using traditional discriminatory markers and new markers of seromucinous differentiation. Twenty-three non-ITAC, 17 ITAC, and 5 SSH were retrieved (1987-2014). As expected, ITAC occurred predominantly in the nasal cavity in elderly patients (mean age 65 years) with a striking male predilection (15:2). Regardless of grade/subtype, all ITAC were invariably CK20 and CDX2 positive, and many (11/15) showed some CK7 positivity. Non-ITAC occurred in younger individuals (mean age 51 years) with a slight female predilection (male to female ratio: 10:13) and showed diverse morphologic patterns and grades, some with morphologic similarity to SSH. SSH occurred in younger individuals (mean age 33 years). Non-ITAC and SSH were invariably CK7 positive and CK20 negative, however, 4/22 non-ITAC and 2/5 SSH showed squamoid morular metaplasia that aberrantly expressed CDX2 and co-expressed nuclear β-catenin. Markers of seromucinous differentiation (S100, DOG1, and SOX10) were essentially absent in ITAC, but present to varying degrees in the majority of non-ITAC and all SSH. Thus, the term 'seromucinous adenocarcinoma' is the more appropriate designation for non-ITAC. Squamoid morules in non-ITAC and SSH may be an immunophenotypic pitfall given the aberrant CDX2 expression. PMID:25690258

  20. [New WHO classification of lung adenocarcinoma and preneoplasia].

    PubMed

    Lantuejoul, Sylvie; Rouquette, Isabelle; Brambilla, Elisabeth; Travis, William D

    2016-01-01

    The 2015 WHO classification of tumors of the lung, pleura, thymus and heart has just been published with numerous important changes from the 2004 WHO classification. The most significant changes involve (1) use of immunohistochemistry throughout the classification, (2) integration of molecular testing for personalized strategies for advanced lung cancer patients, (3) a new classification for small biopsies and cytology, (4) a new classification of lung adenocarcinoma as proposed by the 2011 IASLC/ATS/ERS, (5) restriction of the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation. Regarding adenocarcinoma, the terms bronchioloalveolar carcinoma (BAC) and mixed subtype adenocarcinoma have been suppressed and replaced for the former by the term adenocarcinoma in situ (AIS) as a preinvasive lesion to join atypical adenomatous hyperplasia (AAH). A new category has been defined, the minimally invasive adenocarcinoma (MIA), and invasive adenocarcinomas are now classified according to the predominant subtype after subtyping by semi-quantitatively percentage of various subtypes present in 5% increments. The term "lepidic" is restricted to a non-invasive component (previously classified as BAC) present as part of an invasive adenocarcinoma. "Invasive mucinous adenocarcinoma" is used for formerly adenocarcinomas classified as mucinous BAC, excluding tumors that meet criteria for AIS or MIA. The subtypes of clear cell and signet ring adenocarcinoma are discontinued, as well the term of mucinous cystadenocarcinoma, included in the category of colloid adenocarcinoma. Thus new classification of lung adenocarcinoma is sustained by genetics and has clinical impact for therapeutic strategies. PMID:26791238

  1. CA 15–3 cell lines and tissue expression in canine mammary cancer and the correlation between serum levels and tumour histological grade

    PubMed Central

    2012-01-01

    Background Mammary tumours are the most common malignancy diagnosed in female dogs and a significant cause of mortality and morbidity in this species. Carbohydrate antigen (CA) 15–3 is a mucinous glycoprotein aberrantly over-expressed in human mammary neoplasms and one of the most widely used serum tumour markers in women with breast cancer. The aim of this study was to investigate the antigenic analogies of human and canine CA 15–3 and to assess its expression in canine mammary cancer tissues and cell lines. Immunohistochemical expression of CA 15–3 was evaluated in 7 canine mammary cancer cell lines and 50 malignant mammary tumours. As a positive control, the human breast carcinoma cell line MCF7 and tissue were used. To assess CA 15–3 staining, a semi-quantitative method was applied. To confirm the specificity and cross-reactivity of an anti-human CA 15–3 antibody to canine tissues, an immunoblot analysis was performed. We also investigated serum CA 15–3 activity to establish whether its expression could be assigned to several tumour characteristics to evaluate its potential use as a serum tumour marker in the canine mammary oncology field. Results Immunocytochemical analysis revealed CA 15–3 expression in all examined canine mammary cancer cell lines, whereas its expression was confirmed by immunoblot only in the most invasive cells (CMT-W1, CMT-W1M, CMT-W2 and CMT-W2M). In the tissue, an immunohistochemical staining pattern was observed in 34 (68%) of the malignant tumours. A high statistical correlation (p = 0.0019) between serum CA 15–3 levels and the degree of tumour proliferation and differentiation was shown, which indicates that the values of this serum marker increase as the tumour stage progresses. Conclusions The results of this study reveal that CA 15–3 is expressed in both canine mammary tumour cell lines and tissues and that serum levels significantly correlate with the histological grade of the malignancy. PMID:22726603

  2. Facial dog attack injuries.

    PubMed

    Lin, Wei; Patil, Pavan Manohar

    2015-02-01

    The exposed position of the face makes it vulnerable to dog bite injuries. This fact combined with the short stature of children makes them a high-risk group for such attacks. In contrast to wounds inflicted by assaults and accidents, dog bite wounds are deep puncture type wounds compounded by the presence of pathologic bacteria from the saliva of the attacking dog. This, combined with the presence of crushed, devitalized tissue makes these wounds highly susceptible to infection. Key to successful management of such wounds are meticulous cleansing of the wound, careful debridement, primary repair, appropriate antibiotic therapy, and rabies and tetanus immunization where indicated. This review presents an overview of the epidemiology, presentation, management of such emergencies, and the recent advances in the care of such patients. PMID:25829713

  3. Inhibition of the transient receptor potential melastatin-2 channel causes increased DNA damage and decreased proliferation in breast adenocarcinoma cells

    PubMed Central

    HOPKINS, MANDI M.; FENG, XIAOXING; LIU, MENGWEI; PARKER, LAUREN P.; KOH, DAVID W.

    2015-01-01

    Transient receptor potential, melastatin-2 (TRPM2) is a plasma membrane cation channel with important roles in sensory functions and promoting cell death. However, we demonstrated here that TRPM2 was present in the nuclei of MCF-7 and MDA-MB-231 human breast adenocarcinoma cells, and its pharmacologic inhibition or RNAi silencing caused decreased cell proliferation. Neither an effect on proliferation nor a localization of TRPM2 in the nucleus was observed in noncancerous HMEC and MCF-10A human mammary epithelial cells. Investigation of possible effects of TRPM2 function in the nucleus demonstrated that pharmacologic inhibition or RNAi silencing of TRPM2 in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells caused up to 4-fold increases in DNA damage levels, as compared to noncancerous breast cells after equivalent treatments. These results indicate that TRPM2 has a novel nuclear function in human breast adenocarcinoma cells that facilitates the integrity of genomic DNA, a finding that is distinct from its previously reported role as a plasma membrane cation channel in noncancerous cells. In summary, we report here a novel effect promoted by TRPM2, where it functions to minimize DNA damage and thus may have a role in the protection of genomic DNA in breast cancer cells. Our study therefore provides compelling evidence that TRPM2 has a unique role in breast adenocarcinoma cells. Accordingly, these studies suggest that TRPM2 is a potential therapeutic target, where its pharmacologic inhibition may provide an innovative strategy to selectively increase DNA damage levels in breast cancer cells. PMID:25760245

  4. An autoregulatory enhancer controls mammary-specific STAT5 functions

    PubMed Central

    Metser, Gil; Shin, Ha Youn; Wang, Chaochen; Yoo, Kyung Hyun; Oh, Sumin; Villarino, Alejandro V.; O'Shea, John J.; Kang, Keunsoo; Hennighausen, Lothar

    2016-01-01

    Signal Transducers and Activators of Transcription (STATs) are principal transcription factors downstream of cytokine receptors. Although STAT5A is expressed in most tissues it remains to be understood why its premier, non-redundant functions are restricted to prolactin-induced mammary gland development and function. We report that the ubiquitously expressed Stat5a/b locus is subject to additional lineage-specific transcriptional control in mammary epithelium. Genome-wide surveys of epigenetic status and transcription factor occupancy uncovered a putative mammary-specific enhancer within the intergenic sequences separating the two Stat5 genes. This region exhibited several hallmarks of genomic enhancers, including DNaseI hypersensitivity, H3K27 acetylation and binding by GR, NFIB, ELF5 and MED1. Mammary-specific STAT5 binding was obtained at two canonical STAT5 binding motifs. CRISPR/Cas9-mediated genome editing was used to delete these sites in mice and determine their biological function. Mutant animals exhibited an 80% reduction of Stat5 levels in mammary epithelium and a concomitant reduction of STAT5-dependent gene expression. Transcriptome analysis identified a class of mammary-restricted genes that was particularly dependent on high STAT5 levels as a result of the intergenic enhancer. Taken together, the mammary-specific enhancer enables a positive feedback circuit that contributes to the remarkable abundance of STAT5 and, in turn, to the efficacy of STAT5-dependent mammary physiology. PMID:26446995

  5. Bovine Mammary Epithelial Cell Lineages and Parenchymal Development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary development proceeds from an aggregation of cells in the ventral ectoderm to the establishment of an elaborate tree of alveoli, ducts, and cisternae. However, despite abundant data on endocrine regulation of ruminant mammary growth, we know comparatively little about cell lineages, express...

  6. Bovine mammary stem cells: Cell biology meets production agriculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...

  7. Mammary Development and Breast Cancer: A Wnt Perspective

    PubMed Central

    Yu, Qing Cissy; Verheyen, Esther M.; Zeng, Yi Arial

    2016-01-01

    The Wnt pathway has emerged as a key signaling cascade participating in mammary organogenesis and breast oncogenesis. In this review, we will summarize the current knowledge of how the pathway regulates stem cells and normal development of the mammary gland, and discuss how its various components contribute to breast carcinoma pathology. PMID:27420097

  8. Mammary Development and Breast Cancer: A Wnt Perspective.

    PubMed

    Yu, Qing Cissy; Verheyen, Esther M; Zeng, Yi Arial

    2016-01-01

    The Wnt pathway has emerged as a key signaling cascade participating in mammary organogenesis and breast oncogenesis. In this review, we will summarize the current knowledge of how the pathway regulates stem cells and normal development of the mammary gland, and discuss how its various components contribute to breast carcinoma pathology. PMID:27420097

  9. Pim-1 kinase expression during murine mammary development

    SciTech Connect

    Gapter, Leslie A.; Magnuson, Nancy S.; Ng, Ka-yun; Hosick, Howard L. . E-mail: hosick@wsu.edu

    2006-07-07

    Pim-1 kinase phosphorylates substrates whose activities are linked to proliferation, survival, differentiation, and apoptosis. Although pim-1 is induced by hormones and cytokines, the hormonal control and contribution of Pim-1 to mammary gland development have not been evaluated. We examined Pim-1 expression in mammary cell lines, investigated whether Pim-1 levels could be altered in breast epithelia by mammogenic hormones, and evaluated Pim-1 expression during mammary development. We found that Pim-1 was elevated in most mammary carcinoma cell lines and progesterone increased Pim-1 protein to some extent in non-tumorigenic mammary epithelia. Pim-1 expression in situ was consistent with the documented profile of progesterone activity in mouse mammary glands. Pim-1 nuclear localization correlated with cytoplasmic distribution for its substrate, p21{sup CIP/Waf1}, and we found that Pim-1 and p21 associate in vitro. Our results suggest that Pim-1 expression may be regulated by progesterone during mammary development and Pim-1 associates with p21 in mammary epithelial cells.

  10. Roles of Fas and Fas ligand during mammary gland remodeling

    PubMed Central

    Song, Joon; Sapi, Eva; Brown, Wendi; Nilsen, Jon; Tartaro, Karrie; Kacinski, Barry M.; Craft, Joseph; Naftolin, Frederick; Mor, Gil

    2000-01-01

    Mammary involution is associated with degeneration of the alveolar structure and programmed cell death of mammary epithelial cells. In this study, we evaluated the expression of Fas and Fas ligand (FasL) in the mammary gland tissue and their possible role in the induction of apoptosis of mammary cells. FasL-positive cells were observed in normal mammary epithelium from pregnant and lactating mice, but not in nonpregnant/virgin mouse mammary tissue. Fas expression was observed in epithelial and stromal cells in nonpregnant mice but was absent during pregnancy. At day 1 after weaning, high levels of both Fas and FasL proteins and caspase 3 were observed and coincided with the appearance of apoptotic cells in ducts and glands. During the same period, no apoptotic cells were found in the Fas-deficient (MRL/lpr) and FasL-deficient (C3H/gld) mice. Increase in Fas and FasL protein was demonstrated in human (MCF10A) and mouse (HC-11) mammary epithelial cells after incubation in hormone-deprived media, before apoptosis was detected. These results suggest that the Fas-FasL interaction plays an important role in the normal remodeling of mammary tissue. Furthermore, this autocrine induction of apoptosis may prevent accumulation of cells with mutations and subsequent neoplastic development. Failure of the Fas/FasL signal could contribute to tumor development. PMID:11086022

  11. Mammary Development and Breast Cancer: The Role of Stem Cells

    PubMed Central

    Ercan, C.; van Diest, P.J.; Vooijs, M.

    2014-01-01

    The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation and involution, a process controlled by stem cells. The last decade much progress has been made in the identification of signaling pathways that function in these stem cells to control self-renewal, lineage commitment and epithelial differentiation in the normal mammary gland. The same signaling pathways that control physiological mammary development and homeostasis are also often found deregulated in breast cancer. Here we provide an overview on the functional and molecular identification of mammary stem cells in the context of both normal breast development and breast cancer. We discuss the contribution of some key signaling pathways with an emphasis on Notch receptor signaling, a cell fate determination pathway often deregulated in breast cancer. A further understanding of the biological roles of the Notch pathway in mammary stem cell behavior and carcinogenesis might be relevant for the development of future therapies. PMID:21506923

  12. Huntingtin regulates mammary stem cell division and differentiation.

    PubMed

    Elias, Salah; Thion, Morgane S; Yu, Hua; Sousa, Cristovao Marques; Lasgi, Charlène; Morin, Xavier; Humbert, Sandrine

    2014-04-01

    Little is known about the mechanisms of mitotic spindle orientation during mammary gland morphogenesis. Here, we report the presence of huntingtin, the protein mutated in Huntington's disease, in mouse mammary basal and luminal cells throughout mammogenesis. Keratin 5-driven depletion of huntingtin results in a decreased pool and specification of basal and luminal progenitors, and altered mammary morphogenesis. Analysis of mitosis in huntingtin-depleted basal progenitors reveals mitotic spindle misorientation. In mammary cell culture, huntingtin regulates spindle orientation in a dynein-dependent manner. Huntingtin is targeted to spindle poles through its interaction with dynein and promotes the accumulation of NUMA and LGN. Huntingtin is also essential for the cortical localization of dynein, dynactin, NUMA, and LGN by regulating their kinesin 1-dependent trafficking along astral microtubules. We thus suggest that huntingtin is a component of the pathway regulating the orientation of mammary stem cell division, with potential implications for their self-renewal and differentiation properties. PMID:24749073

  13. Mammary Analogue Secretory Carcinoma (MASC) of salivary gland in four Mexican patients

    PubMed Central

    Mosqueda-Taylor, Adalberto; Domínguez-Malagón, Hugo; Michal, Michal

    2015-01-01

    The Clinco-pathological, immunohistochemical and molecular findings of four cases of Mammary Analogue Secretory Carcinoma (MASC) of salivary glands found in Mexico are described. The cases were extracted from 253 salivary gland tumors from a single institution in Mexico City. The 85 candidates for initial selection were: low grade mucoepidermoid carcinoma (MEC) (N=70 ), acinic cell cancinoma (AciCC) (N=14), papillary cystadenocarcinoma (N=1), and adenocarcinoma NOS (N=0). Tumors with some histological features consistent with MASC (N= 17, 6.7%) were studied by immunohistochemistry for mammaglobin, STAT5, and S-100 protein and four cases were positive (1.5%), thus the diagnosis of MASC was established, and these were submitted for molecular studies for ETV6-NTRK3. Fusion gene was demonstrated in three cases, two had been erroneously diagnosed as poorly granulated AciCC, and one as low grade MEC with microcystic pattern. Female gender predominated (3:1); one occurred in the parotid, two in minor salivary glands and one in the submaxillary gland; infiltrating borders, atypical mitosis and lymph node metastases were seen in the parotideal tumor. Two patients with major salivary gland tumors are alive and well at 10 and 20 months respectively, the two patients with minor salivary gland tumors are lost. It can be concluded that is important to think in MASC in poorly granulated AciCC and low grade MEC with microcystic pattern. Immunohistochemisty studies confirm the diagnosis, preferentially supported by molecular studies. MASC may follow aggressive behavior or transform into a high grade neoplasm. Key words:Acinic cell carcinoma, ETV6-NTRK3, Mammary Analogue Secretory Carcinoma, secretory breast carcinoma. PMID:25481229

  14. Carcinogenic responses to chemicals applied directly to rat mammary glands in situ

    SciTech Connect

    Holtzman, S.; Meade, M.; Stone, J.P.; Shellabarger, C.J.

    1985-01-01

    In four experiments, concentrated glycerin suspensions of 7,12-dimethylbenz(a)anthracene (DMBA), or the water-soluble compounds, N-methyl-N-nitrosourea (MNU), N-ethyl-N-nitrosourea (ENU), and 4-nitroquinoline-N-oxide (4-NQO) were delivered into pockets in the mammary fat pads in female Sprague-Dawley rats. In a 90-day experiment, each of three groups of 20-22 rats were treated with either 25, 50, or 100 ..mu..g DMBA delivered to each of four sites in each rat per group. Dose-related responses were detected for incidence of rats with mammary adenocarcinoma (MAC), and for number of MAC per treated site. In a 120-day study, each of three groups of 20 animals were treated with either 250, 500, or 1000 ..mu..g MNU at each of 80 sites per group. Dose-related MAC responses were detected for incidence of rats with MAC, number of MAC per treated site, and time to detection of MAC. In two experiments of 90 days duration, groups of 20 females were treated with either 1000 ..mu..g ENU or 1000 ..mu..g 4-NQO at each of 80 sites per group. ENU produced a total of 27 MAC sites in 65% of the rats, and 4-NQO produced a total of 26 MAC in 60% of the rats. A comparison of the time to detection of all MAC data for the three water-soluble compounds at the 1000 ..mu..g treatment level, or on the basis of moles per treatment, yielded a carcinogenic potency relationship of 4-NQO > ENU > MNU. 21 references, 2 figures, 1 table.

  15. Adenocarcinoma - chest x-ray (image)

    MedlinePlus

    This chest x-ray shows adenocarcinoma of the lung. There is a rounded light spot in the right upper lung (left side ... density. Diseases that may cause this type of x-ray result would be tuberculous or fungal granuloma, and ...

  16. Gene expression profiling analysis of lung adenocarcinoma

    PubMed Central

    Xu, H.; Ma, J.; Wu, J.; Chen, L.; Sun, F.; Qu, C.; Zheng, D.; Xu, S.

    2016-01-01

    The present study screened potential genes related to lung adenocarcinoma, with the aim of further understanding disease pathogenesis. The GSE2514 dataset including 20 lung adenocarcinoma and 19 adjacent normal tissue samples from 10 patients with lung adenocarcinoma aged 45-73 years was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the two groups were screened using the t-test. Potential gene functions were predicted using functional and pathway enrichment analysis, and protein-protein interaction (PPI) networks obtained from the STRING database were constructed with Cytoscape. Module analysis of PPI networks was performed through MCODE in Cytoscape. In total, 535 upregulated and 465 downregulated DEGs were identified. These included ATP5D, UQCRC2, UQCR11 and genes encoding nicotinamide adenine dinucleotide (NADH), which are mainly associated with mitochondrial ATP synthesis coupled electron transport, and which were enriched in the oxidative phosphorylation pathway. Other DEGs were associated with DNA replication (PRIM1, MCM3, and RNASEH2A), cell surface receptor-linked signal transduction and the enzyme-linked receptor protein signaling pathway (MAPK1, STAT3, RAF1, and JAK1), and regulation of the cytoskeleton and phosphatidylinositol signaling system (PIP5K1B, PIP5K1C, and PIP4K2B). Our findings suggest that DEGs encoding subunits of NADH, PRIM1, MCM3, MAPK1, STAT3, RAF1, and JAK1 might be associated with the development of lung adenocarcinoma. PMID:26840709

  17. Vanishing native American dog lineages

    PubMed Central

    2011-01-01

    Background Dogs were an important element in many native American cultures at the time Europeans arrived. Although previous ancient DNA studies revealed the existence of unique native American mitochondrial sequences, these have not been found in modern dogs, mainly purebred, studied so far. Results We identified many previously undescribed mitochondrial control region sequences in 400 dogs from rural and isolated areas as well as street dogs from across the Americas. However, sequences of native American origin proved to be exceedingly rare, and we estimate that the native population contributed only a minor fraction of the gene pool that constitutes the modern population. Conclusions The high number of previously unidentified haplotypes in our sample suggests that a lot of unsampled genetic variation exists in non-breed dogs. Our results also suggest that the arrival of European colonists to the Americas may have led to an extensive replacement of the native American dog population by the dogs of the invaders. PMID:21418639

  18. Mammary epithelial cells isolated from milk are a valuable, non-invasive source of mammary transcripts

    PubMed Central

    Boutinaud, Marion; Herve, Lucile; Lollivier, Vanessa

    2015-01-01

    Milk is produced in the udder by mammary epithelial cells (MEC). Milk contains MEC, which are gradually exfoliated from the epithelium during lactation. Isolation of MEC from milk using immunomagnetic separation may be a useful non-invasive method to investigate transcriptional regulations in ruminants’ udder. This review aims to describe the process of isolating MEC from milk, to provide an overview on the studies that use this method to analyze gene expression by qRT PCR and to evaluate the validity of this method by analyzing and comparing the results between studies. In several goat and cow studies, consistent reductions in alpha-lactalbumin mRNA levels during once-daily milking (ODM) and in SLC2A1 mRNA level during feed restriction are observed. The effect of ODM on alpha-lactalbumin mRNA level was similarly observed in milk isolated MEC and mammary biopsy. Moreover, we and others showed decreasing alpha-lactalbumin and increasing BAX mRNA levels with advanced stages of lactation in dairy cows and buffalo. The relevance of using the milk-isolated MEC method to analyze mammary gene expression is proven, as the transcript variations were also consistent with milk yield and composition variations under the effect of different factors such as prolactin inhibition or photoperiod. However, the RNA from milk-isolated MEC is particularly sensitive to degradation. This could explain the differences obtained between milk-isolated MEC and mammary biopsy in two studies where gene expression was compared using qRT-PCR or RNA Sequencing analyses. As a conclusion, when the RNA quality is conserved, MEC isolated from milk are a valuable, non-invasive source of mammary mRNA to study various factors that impact milk yield and composition (ODM, feeding level, endocrine status, photoperiod modulation, and stage of lactation). PMID:26579195

  19. Periampullary adenocarcinoma: analysis of 5-year survivors.

    PubMed Central

    Yeo, C J; Sohn, T A; Cameron, J L; Hruban, R H; Lillemoe, K D; Pitt, H A

    1998-01-01

    OBJECTIVE: This single-institution experience retrospectively reviews the outcomes in a group of patients treated 5 or more years ago by pancreaticoduodenectomy for periampullary adenocarcinoma. SUMMARY BACKGROUND DATA: Controversy exists regarding the benefit of resection for periampullary adenocarcinoma, particularly for pancreatic tumors. Many series report only Kaplan-Meier actuarial 5-year survival rates. There are believed to be discrepancies between the actuarial 5-year survival data and the actual 5-year survival rates. METHODS: From April 1970 through May 1992, 242 patients underwent pancreaticoduodenal resection for periampullary adenocarcinoma at The Johns Hopkins Hospital. Follow-up was complete through May 1997. All pathology specimens were reviewed and categorized. Actual 5-year survival rates were calculated. The demographic, intraoperative, pathologic, and postoperative features of patients surviving > or =5 years were compared with those of patients who survived <5 years. RESULTS: Of the 242 patients with resected periampullary adenocarcinoma, 149 (62%) were pancreatic primaries, 46 (19%) arose in the ampulla, 30 (12%) were distal bile duct cancers, and 17 (7%) were duodenal cancers. There was a 5.3% operative mortality rate during the 22 years of the review, with a 2% operative mortality rate in the last 100 patients. There were 58 5-year survivors, 28 7-year survivors, and 7 10-year survivors. The tumor-specific 5-year actual survival rates were pancreatic 15%, ampullary 39%, distal bile duct 27%, and duodenal 59%. When compared with patients who did not survive 5 years, the 5-year survivors had a significantly higher percentage of well-differentiated tumors (14% vs. 4%; p = 0.02) and higher incidences of negative resection margins (98% vs. 73%, p < 0.0001) and negative nodal status (62% vs. 31%, p < 0.0001). The tumor-specific 10-year actuarial survival rates were pancreatic 5%, ampullary 25%, distal bile duct 21%, and duodenal 59%. CONCLUSIONS

  20. Genistein-mediated inhibition of mammary stromal adipocyte differentiation limits expansion of mammary stem/progenitor cells by paracrine signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary adiposity may contribute to breast cancer development and progression by releasing cytokines and other inflammatory mediators that promote mammary epithelial proliferation. We evaluated the effects of soy isoflavone genistein (GEN) on the adipogenic differentiation of a SV40-immortalized mou...

  1. Early Effects of Blueberry and Concord Grape Intake on Rat Mammary Gland Development Suggest Potential Protective Mechanisms for Mammary Tumorigenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blueberries (BB) and Concord grapes (CG) are rich in anthocyanins and other polyphenols, which may be linked to reduced incidence of chemically induced mammary carcinogenesis in animal models. We evaluated the early effects of dietary exposure to BB and CG on mammary glands of female rat offspring. ...

  2. Chemoprevention of rat mammary carcinogenesis by black tea polyphenols: modulation of xenobiotic-metabolizing enzymes, oxidative stress, cell proliferation, apoptosis, and angiogenesis.

    PubMed

    Kumaraguruparan, R; Seshagiri, P B; Hara, Y; Nagini, S

    2007-09-01

    Chemoprevention of dietary constituents has emerged as a cost-effective approach to control the incidence of breast cancer. The present study was therefore designed to evaluate the chemopreventive efficacy of black tea polyphenols (Polyphenon-B) during the preinitiation phase of 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinogenesis using xenobiotic-metabolizing enzymes, cellular redox status, cell proliferation, apoptosis, and angiogenesis as biomarkers of chemoprevention. Intragastric administration of DMBA induced adenocarcinomas that showed enhanced activities of phase I carcinogen activation and phase II detoxification enzymes with increased lipid and protein oxidation and decrease in antioxidant status. This was associated with increased cell proliferation, angiogenesis, and evasion of apoptosis as revealed by upregulation of proliferating cell nuclear antigen (PCNA), Bcl-2, and vascular endothelial growth factor (VEGF), and downregulation of Bax, caspase 3, and poly(ADP-ribose) polymerase (PARP). Dietary administration of Polyphenon-B effectively suppressed the incidence of mammary tumors as evidenced by modulation of xenobiotic-metabolizing enzymes and oxidant-antioxidant status, inhibition of cell proliferation and angiogenesis, and induction of apoptosis. The present study provides evidence that Polyphenon-B exerts multifunctional inhibitory effects on DMBA-induced mammary carcinogenesis and suggests that it can be developed as a potential chemopreventive agent. PMID:17415784

  3. Whey Protein Hydrolysate but not Whole Whey Protein Protects Against 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumors in Rats.

    PubMed

    Ronis, Martin J; Hakkak, Reza; Korourian, Soheila; Badger, Thomas M

    2015-01-01

    Effects of intact and processed bovine milk proteins on development of chemically induced mammary tumors in female rats were compared. AIN-93G diets were made with 20% casein (CAS), casein hydrolysate (CASH), intact whey protein (IWP), or whey protein hydrolysate (WPH). Pregnant Sprague-Dawley rats were fed the diets starting at Gestational Day 4. Offspring were fed the same diet. At 50 days, female offspring (44-49/group) were gavaged with sesame oil containing 80 mg/kg of the mammary carcinogen dimethylbenzanthracene (DMBA) and euthanized 62 days posttreatment. Rats fed WPH had an adenocarcinoma incidence of 17% compared to the rats fed CAS, CASH, and IWP diets (34%, 33%, and 36% respectively) (P < 0.001). Median palpable tumor latency for rats fed WPH was greater (61 days, P < 0.001) compared to CAS (44 days), CASH (42 days) and IWP (45 days). Tumor multiplicity was also lower (1.5 vs. 3.0, P < 0.05) in rats fed WPH than in CAS and CASH fed groups. Results demonstrate that hydrolytic processing of whey protein is required for this diet to be effective in reducing DMBA-induced mammary tumors. The bioactive compounds produced during whey protein processing and mechanisms underlying the anticancer effects of WPH are yet to be identified. PMID:26168336

  4. Susceptibility of fetal, virgin, pregnant and lactating rats for the induction of mammary tumors by gamma rays

    SciTech Connect

    Inano, Hiroshi; Suzuki, Heiko; Onoda, Makoto; Yamanouchi, Hiroshi

    1996-06-01

    Pregnant Wistar-MS rats received a whole-body irradiation of 0-2.6 Gy {gamma} rays at day 20 of pregnancy. The mother rats were implanted with a diethylstilbestrol (DES) pellet 30 days after weaning, and the female pups delivered by the irradiated mother were treated with DES after maturation. Lactating rats were irradiated with {gamma} rays 21 days after parturition and then treated with DES. Virgin rats 70 days of age were also irradiated and then administered DES. The rats which received intrauterine irradiation did not develop mammary tumors in the mother rats and lactating rats increased in a dose-dependent manner with increasing doses of {gamma} rays up to 2.1 Gy. With 0.1-1 Gy, the incidence of adenocarcinoma in the mother rats was significantly lower than that observed in the lactating rats. However, the incidence in the mother rats irradiated with 1.0-1.5 Gy was significantly higher than that of virgin rats treated with the corresponding {gamma}-ray doses. These findings suggest that the susceptibility of the mammary glands to radiation depends upon the differentiation at the time of exposure. 22 refs., 4 figs., 2 tabs.

  5. Automatic imitation in dogs

    PubMed Central

    Range, Friederike; Huber, Ludwig; Heyes, Cecilia

    2011-01-01

    After preliminary training to open a sliding door using their head and their paw, dogs were given a discrimination task in which they were rewarded with food for opening the door using the same method (head or paw) as demonstrated by their owner (compatible group), or for opening the door using the alternative method (incompatible group). The incompatible group, which had to counterimitate to receive food reward, required more trials to reach a fixed criterion of discrimination performance (85% correct) than the compatible group. This suggests that, like humans, dogs are subject to ‘automatic imitation’; they cannot inhibit online the tendency to imitate head use and/or paw use. In a subsequent transfer test, where all dogs were required to imitate their owners' head and paw use for food reward, the incompatible group made a greater proportion of incorrect, counterimitative responses than the compatible group. These results are consistent with the associative sequence learning model, which suggests that the development of imitation depends on sensorimotor experience and phylogenetically general mechanisms of associative learning. More specifically, they suggest that the imitative behaviour of dogs is shaped more by their developmental interactions with humans than by their evolutionary history of domestication. PMID:20667875

  6. Zen Hot Dog Molecules

    ERIC Educational Resources Information Center

    Ryan, Dennis

    2009-01-01

    Substituted cycloalkanes with one branch illustrating each topic in an instructional unit can serve as summaries or reviews in courses of organic chemistry. The hungry Zen master told the hot dog vendor to make him one with everything. You can do the same for your students.

  7. Zen Hot Dog Molecules

    NASA Astrophysics Data System (ADS)

    Ryan, Dennis

    2009-04-01

    Substituted cycloalkanes with one branch illustrating each topic in an instructional unit can serve as summaries or reviews in courses of organic chemistry. The hungry Zen master told the hot dog vendor to make him one with everything. You can do the same for your students.

  8. Neosporosis in dogs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Neospora caninum is a protozoan parasite of animals. Until 1988, it was misdiagnosed as Toxoplasma gondii. Since its first recognition in 1984 and the description of a new genus and species Neospora caninum in 1988, neosporosis has emerged as a serious disease of dogs and cattle worldwide. Additiona...

  9. Sensitivity of locally recurrent rat mammary tumour cell lines to syngeneic polymorphonuclear cell, macrophage and natural killer cell cytolysis.

    PubMed

    Aeed, P A; Welch, D R

    1988-12-01

    Using a recently developed model for studying the biology of locally recurrent (LR) mammary tumours in the 13762NF rat mammary adenocarcinoma system, we examined the sensitivity to polymorphonuclear cell, macrophage and natural killer cell cytolysis. The parental MTF7(T20) cell line; the 'primary' tumours which arose following subcutaneous inoculation into the mammary fat pad, sc1 and sc3; and the local recurrences (following surgical excision) LR1 and LR1a from sc1, and LR3 from sc3 were all cells generally resistant to specific PMN cytolysis. LPS-activated macrophages caused 25.1%, 38.7% and 58.8% specific cytolysis in MTF7, sc1 and LR1 cells, respectively at E:T of 20:1 and 72 h co-incubation. LR1a, sc3 and LR3 lysis ranged from 0-4.4% under the same conditions. Non-activated macrophages did not lyse any of the cell lines. Locally recurrent and 'primary' tumour cell lines were also not lysed by naive NK cells (range 0.5-4.0% cytolysis). NK cells activated with bropirimine, a potent immunomodulator currently being studied in clinical trials, and/or interleukin-2 were mildly more effective at killing LR cells. Our results show that locally recurrent tumours exhibit heterogeneous sensitivities and are different from 'primary' tumour cells in sensitivities to immune cell killing, but they are not necessarily more or less sensitive. Results with bropirimine-activated or IL-2-activated NK cells emphasize that nonspecific activation is insufficient to eliminate all tumour subpopulations. PMID:3224080

  10. Peroxisome proliferator-activated receptor-binding protein null mutation results in defective mammary gland development.

    PubMed

    Jia, Yuzhi; Qi, Chao; Zhang, Zhongyi; Zhu, Yiwei Tony; Rao, Sambasiva M; Zhu, Yi-Jun

    2005-03-18

    A conditional null mutation of peroxisome proliferator-activated receptor-binding protein (PBP) gene was generated to understand its role in mammary gland development. PBP-deficient mammary glands exhibited retarded ductal elongation during puberty, and decreased alveolar density during pregnancy and lactation. PBP-deficient mammary glands could not produce milk to nurse pups during lactation. Both the mammary ductal elongation in response to estrogen treatment and the mammary lobuloalveolar proliferation stimulated by estrogen plus progesterone were attenuated in PBP-deficient mammary glands. The proliferation index was decreased in PBP-deficient mammary glands. PBP-deficient mammary epithelial cells expressed abundant beta-casein, whey acidic protein, and WDNM1 mRNA, indicating a relatively intact differentiated function. PBP-deficient epithelial cells were unable to form mammospheres, which were considered to be derived from mammary progenitor/stem cells. We conclude that PBP plays a pivotal role in the normal mammary gland development. PMID:15647257

  11. Raising gestational choline intake alters gene expression in DMBA-evoked mammary tumors and prolongs survival

    PubMed Central

    Kovacheva, Vesela P.; Davison, Jessica M.; Mellott, Tiffany J.; Rogers, Adrianne E.; Yang, Shi; O'Brien, Michael J.; Blusztajn, Jan Krzysztof

    2009-01-01

    Choline is an essential nutrient that serves as a donor of metabolic methyl groups used during gestation to establish the epigenetic DNA methylation patterns that modulate tissue-specific gene expression. Because the mammary gland begins its development prenatally, we hypothesized that choline availability in utero may affect the gland’s susceptibility to cancer. During gestational days 11–17, pregnant rats were fed a control, choline-supplemented, or choline-deficient diet (8, 36, and 0 mmol/kg of choline, respectively). On postnatal day 65, the female offspring received 25 mg/kg of a carcinogen 7,12-dimethylbenz[α]anthracene. Approximately 70% of the rats developed mammary adenocarcinomas; prenatal diet did not affect tumor latency, incidence, size, and multiplicity. Tumor growth rate was inversely related to choline content in the prenatal diet, resulting in 50% longer survival until euthanasia, determined by tumor size, of the prenatally choline-supplemented rats compared with the prenatally choline-deficient rats. This was accompanied by distinct expression patterns of ∼70 genes in tumors derived from the three dietary groups. Tumors from the prenatally choline-supplemented rats overexpressed genes that confer favorable prognosis in human cancers (Klf6, Klf9, Nid2, Ntn4, Per1, and Txnip) and underexpressed those associated with aggressive disease (Bcar3, Cldn12, Csf1, Jag1, Lgals3, Lypd3, Nme1, Ptges2, Ptgs1, and Smarcb1). DNA methylation within the tumor suppressor gene, stratifin (Sfn, 14-3-3σ), was proportional to the prenatal choline supply and correlated inversely with the expression of its mRNA and protein in tumors, suggesting that an epigenetic mechanism may underlie the altered molecular phenotype and tumor growth. Our results suggest a role for adequate maternal choline nutrition during pregnancy in prevention/alleviation of breast cancer in daughters.—Kovacheva, V. P., Davison, J. M., Mellott, T. J., Rogers, A. E., Yang, S., O’Brien, M

  12. Periareolar techniques for mammary reduction and elevation.

    PubMed

    de Benito, J; Sanza, I F

    1993-01-01

    Between June 1990 and June 1992 we carried out 56 breast operations: 18 reductions, 32 mastopexies, and 6 implant changes. The surgical techniques used in all cases basically consisted of three phases: the periareolar incision, the creation of the superior pedicle with two medial and lateral flaps, and the "anchoring," crossed by both flaps in order to hold up the mammary gland. The diameter of the "doughnut" of skin that we had to deepidermize varied between 5 and 15 cm, thus raising the nipple-areola complex by as much as 10 cm. The volume of tissue removed from the hypertrophic breast ranged from 70 to 520 g. In 24 of the 32 mastopexies, the use of a silicone implant was necessary in order to provide greater volume, texture, and better mammary contour. In these cases the size of the prostheses varied between 120 and 300 cc. All patients completed the postop followup in the normal way. Only three patients suffered a slight dehiscence of the periareolar suture, which was solved within a few days of the operation by means of a Friedreich. The periareolar cutaneous pleats and the hardness of the breast gradually disappeared, as predicted, within a period of 3-4 months; afterward the breast looked perfectly natural. PMID:8273533

  13. Progesterone induces adult mammary stem cell expansion.

    PubMed

    Joshi, Purna A; Jackson, Hartland W; Beristain, Alexander G; Di Grappa, Marco A; Mote, Patricia A; Clarke, Christine L; Stingl, John; Waterhouse, Paul D; Khokha, Rama

    2010-06-10

    Reproductive history is the strongest risk factor for breast cancer after age, genetics and breast density. Increased breast cancer risk is entwined with a greater number of ovarian hormone-dependent reproductive cycles, yet the basis for this predisposition is unknown. Mammary stem cells (MaSCs) are located within a specialized niche in the basal epithelial compartment that is under local and systemic regulation. The emerging role of MaSCs in cancer initiation warrants the study of ovarian hormones in MaSC homeostasis. Here we show that the MaSC pool increases 14-fold during maximal progesterone levels at the luteal dioestrus phase of the mouse. Stem-cell-enriched CD49fhi cells amplify at dioestrus, or with exogenous progesterone, demonstrating a key role for progesterone in propelling this expansion. In aged mice, CD49fhi cells display stasis upon cessation of the reproductive cycle. Progesterone drives a series of events where luminal cells probably provide Wnt4 and RANKL signals to basal cells which in turn respond by upregulating their cognate receptors, transcriptional targets and cell cycle markers. Our findings uncover a dynamic role for progesterone in activating adult MaSCs within the mammary stem cell niche during the reproductive cycle, where MaSCs are putative targets for cell transformation events leading to breast cancer. PMID:20445538

  14. Surface scanning: an application to mammary surgery

    NASA Astrophysics Data System (ADS)

    Rigotti, Camilla; Ferrigno, Giancarlo; Aliverti, Andrea; Pedotti, Antonio

    1998-04-01

    The possibility of mathematically describing the body surface represents a useful tool for several medical sectors, such as prosthetics or plastic surgery, and could improve diagnosis and objective evaluation of deformities and the follow-up of progressive diseases. The approach presented is based on the acquisition of a surface scanned by a laser beam. The 3D coordinates of the spot generated on the surface by the laser beam are computed by an automatic image analyzer. Using at least two different views of the subject, the 3D coordinates are obtained by stereophotogrammetry. A software package for graphic representation and extraction of linear superficial and volumetric features from the acquired surface has been developed and some preliminary results with mammary reconstruction are presented. A good mammary reconstruction after mastectomy must achieve two results. First, the reconstruction should follow the patients' wishes and second, the reconstructed breast should be as similar as possible to the contralateral one. To achieve these goals, a knowledge of breast volume, area, and shape features are essential for the surgeon. In such a context, this system could be a valuable tool in improving breast reconstructive surgery.

  15. STAT signaling in mammary gland differentiation, cell survival and tumorigenesis

    PubMed Central

    Haricharan, S; Li, Y

    2013-01-01

    The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. PMID:23541951

  16. Persistent mammary hyperplasia in FVB/N mice.

    PubMed

    Nieto, Ana I; Shyamala, G; Galvez, Jose J; Thordarson, Gudmundur; Wakefield, Lalage M; Cardiff, Robert D

    2003-08-01

    The inbred FVB/N mouse strain is widely used for creating transgenic mice. Over the past decade, persistent mammary hyperplasia has been detected in many multiparous FVB/N female mice sent to the University of California, Davis (UCD) Mutant Mouse Pathology Laboratory (MMPL) by a number of different laboratories. However, the experimental details concerning most specimens were not always available. To confirm these empiric findings, experiments were carried out to evaluate the mammary glands of FVB/N mice under controlled conditions. Persistent mammary hyperplasia that related to parity was found. Weeks after their first to fourth pregnancy, 10 FVB/N female mice from the Lawrence Berkeley National Laboratory (LBNL) colony were studied and the mammary glands were evaluated. The percentage of fat pad filled was estimated, using image analysis. Serum samples and the pituitary gland from other FVB/N mice from the LBNL were assayed for prolactin concentration. Multiparous FVB/N females consistently had persistent mammary hyperplasia. Four of seven females in the LBNL colony had hyperplasia after three pregnancies. A few foci of squamous nodules and sporadic carcinomas also were observed. Thus, some FVB/N females may have persistent mammary hyperplasia after three pregnancies without detectable pituitary abnormalities. Mammary carcinomas also may develop sporadically. These background phenotypes must be considered when interpreting the effect of genetic manipulation in FVB/N mice. PMID:14524420

  17. Mammary gland-specific ablation of focal adhesion kinase reduces the incidence of p53-mediated mammary tumour formation

    PubMed Central

    van Miltenburg, M H A M; van Nimwegen, M J; Tijdens, I; Lalai, R; Kuiper, R; Klarenbeek, S; Schouten, P C; de Vries, A; Jonkers, J; van de Water, B

    2014-01-01

    Background: Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in spontaneous mammary tumour development caused by loss of tumour suppressor genes such as p53 is lacking. Alterations in the tumour suppressor gene p53 have been implicated in over 50% of human breast cancers. Given that elevated FAK expression highly correlates with p53 mutation status in human breast cancer, we set out to investigate the importance of FAK in p53-mediated spontaneous mammary tumour development. Methods: To directly assess the role of FAK, we generated mice with conditional inactivation of FAK and p53. We generated female p53lox/lox/FAK+/+/WapCre, p53lox/lox/FAKflox/+/WapCre and p53lox/lox/FAKflox/−/WapCre mice, and mice with WapCre-mediated conditional expression of p53R270H, the mouse equivalent of human p53R273H hot spot mutation, together with conditional deletion of FAK, P53R270H/+/FAKlox/+/WapCre and p53R270H/+/FAKflox/−/WapCre mice. All mice were subjected to one pregnancy to induce WapCre-mediated deletion of p53 or expression of p53 R270H, and Fak genes flanked by two loxP sites, and subsequently followed the development of mammary tumours. Results: Using this approach, we show that FAK is important for p53-induced mammary tumour development. In addition, mice with the mammary gland-specific conditional expression of p53 point mutation R270H, the mouse equivalent to human R273H, in combination with conditional deletion of Fak showed reduced incidence of p53R270H-induced mammary tumours. In both models these effects of FAK were related to reduced proliferation in preneoplastic lesions in the mammary gland ductal structures. Conclusions: Mammary gland-specific ablation of FAK hampers p53-regulated spontaneous mammary tumour formation. Focal adhesion

  18. Radiographic liver size in Pekingese dogs versus other dog breeds.

    PubMed

    Choi, Jihye; Keh, Seoyeon; Kim, Hyunwook; Kim, Junyoung; Yoon, Junghee

    2013-01-01

    Differential diagnoses for canine liver disease are commonly based on radiographic estimates of liver size, however little has been published on breed variations. Aims of this study were to describe normal radiographic liver size in Pekingese dogs and to compare normal measurements for this breed with other dog breeds and Pekingese dogs with liver disease. Liver measurements were compared for clinically normal Pekingese (n = 61), normal non-Pekingese brachycephalic (n = 45), normal nonbrachycephalic (n = 71), and Pekingese breed dogs with liver disease (n = 22). For each dog, body weight, liver length, T11 vertebral length, thoracic depth, and thoracic width were measured on right lateral and ventrodorsal abdominal radiographs. Liver volume was calculated using a formula and ratios of liver length/T11 vertebral length and liver volume/body weight ratio were determined. Normal Pekingese dogs had a significantly smaller liver volume/body weight ratio (16.73 ± 5.67, P < 0.05) than normal non-Pekingese brachycephalic breed dogs (19.54 ± 5.03) and normal nonbrachycephalic breed dogs (18.72 ± 6.52). The liver length/T11 vertebral length ratio in normal Pekingese (4.64 ± 0.65) was significantly smaller than normal non-Pekingese brachycephalic breed dogs (5.16 ± 0.74) and normal nonbrachycephalic breed dogs (5.40 ± 0.74). Ratios of liver volume/body weight and liver length/T11 vertebral length in normal Pekingese were significantly different from Pekingese with liver diseases (P < 0.05). Findings supported our hypothesis that Pekingese dogs have a smaller normal radiographic liver size than other breeds. We recommend using 4.64× the length of the T11 vertebra as a radiographic criterion for normal liver length in Pekingese dogs. PMID:23094756

  19. Bilious Vomiting Syndrome in Dogs: Retrospective Study of 20 Cases (2002-2012).

    PubMed

    Ferguson, Leah; Wennogle, Sara A; Webb, Craig B

    2016-01-01

    Bilious vomiting syndrome (BVS) is a condition historically associated with early morning vomiting of bile, but it is otherwise poorly characterized. The vomiting is thought to result from a reflux of duodenal fluid into the gastric lumen causing mucosal irritation. Medical records from Colorado State University Veterinary Teaching Hospital (CSUVTH) were searched for "canine" and "bilious vomiting syndrome" between 2002 and 2012. Visual inspection confirmed a diagnosis of BVS during the case history. The diagnosis remained BVS for the duration of the dog's contact with the hospital in 17 cases. Therapy involved frequent feedings, late evening meals, gastric acid reducers, prokinetics, and gastroprotectants. Twelve dogs improved with therapy. Five dogs did not improve or were lost to follow-up. The diagnosis of BVS was supplanted in three cases with gastric adenocarcinoma, dietary indiscretion, and hepatopathy. The patient most likely given a diagnosis of BVS would be a young, mixed-breed, castrated male dog with a chronic history of vomiting bile. Response to therapy suggests abnormal gastrointestinal motility, local gastritis, gastric pH, or stimulation of the emetic center may be important factors in BVS. Dogs diagnosed with BVS rarely received a diagnostic evaluation sufficient to qualify it as a diagnosis of exclusion. PMID:27008323

  20. Sequencing the transcriptome of milk production: milk trumps mammary tissue

    PubMed Central

    2013-01-01

    Background Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. Results We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. Conclusions RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation. PMID:24330573

  1. FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Chemoradiotherapy in Patients With Esophageal Adenocarcinoma

    ClinicalTrials.gov

    2016-02-16

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Gastric Cardia; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer; Stage IIIC Esophageal Cancer

  2. Xylitol and Your Dog: Danger, Paws Off

    MedlinePlus

    ... Home For Consumers Consumer Updates Xylitol and Your Dog: Danger, Paws Off Share Tweet Linkedin Pin it ... back to top Why is Xylitol Dangerous to Dogs, but Not People? In both people and dogs, ...

  3. Bilateral internal mammary arteries: evidence and technical considerations

    PubMed Central

    Edelman, J. James B.; Wilson, Michael K.

    2013-01-01

    Bilateral internal mammary artery (BIMA) grafts are used for coronary revascularisation by only a minority of surgeons, despite a growing body of evidence suggesting improved survival when compared to use of only one internal mammary artery with additional saphenous vein grafts. Herein we review the evidence supporting revascularisation with BIMA and suggest reasons why the majority of surgeons use only one internal mammary artery. We discuss technical considerations, various graft combinations and the use of BIMA to facilitate anaortic off-pump coronary artery bypass (OPCAB). PMID:23977638

  4. Chemoprevention of mammary tumor virus-induced and chemical carcinogen-induced rodent mammary tumors by natural plant products.

    PubMed

    Bhide, S V; Azuine, M A; Lahiri, M; Telang, N T

    1994-01-01

    The natural plant products turmeric, beta-carotene, catechin, and betel leaf extract were evaluated for their antitumor effects on mammary tumorigenesis in murine mammary tumor expressing C3H (Jax) mice and in Wistar rats treated with the chemical carcinogen 7-12-dimethylbenz(a)anthracene (DMBA). Administration of turmeric through the diet and of beta-carotene, catechin, and betel leaf extract through the drinking water to virgin female C3H mice resulted in decreased tumor incidence and tumor burden. Administering 5% turmeric in the diet from 2 months of age showed suppression of mammary tumor virus-related reverse transcriptase activity and of preneoplastic changes in the mammary glands. Furthermore, feeding turmeric from 6 months of age resulted in a 100% inhibition of mammary tumors. In the DMBA model of rat mammary tumorigenesis, administration of turmeric, catechin, and betel leaf extract resulted in decreased tumor burden and tumor incidence, and a delay in the onset of mammary tumors. PMID:7526904

  5. FRY site-specific methylation differentiates pancreatic ductal adenocarcinoma from other adenocarcinomas.

    PubMed

    Srisuttee, Ratakorn; Ota, Jun; Muangsub, Tachapol; Keelawat, Somboon; Trirattanachat, Surang; Kitkumthorn, Nakarin; Mutirangura, Apiwat

    2016-06-01

    Adenocarcinoma is a type of cancer that occurs in the glandular cells throughout the body. There are several metastatic adenocarcinoma of unknown primary origin. Currently, there is no highly effective method to differentiate pancreatic ductal adenocarcinoma (PDAC) from other adenocarcinomas. Here, we identified pancreas tissue by site-specific methylation at FRY and found that it can also detect PDAC. The establishment of Combined Bisulphite Restriction Analysis (COBRA) and quantitative real-time PCR techniques of FRY revealed FRY hypermethylation in 21 out of 24 normal pancreatic tissue samples, whereas all other normal tissue samples from thirteen other organs (80 samples) remained totally unmethylated. Similarly in application to PDAC, this marker effectively indicated 25 PDAC among 151 other common adenocarcinomas with values of 100%, 98.7%, 92.6%, and 100% in sensitivity, specificity, positive predictive value and negative predictive value, respectively. In summary, we have demonstrated that this epigenetic site-specific marker has high potential for pancreatic tissue identification and can be applied in PDAC diagnosis. PMID:26990916

  6. Changing rates of adenocarcinoma of the lung.

    PubMed

    Burns, David M

    2014-08-18

    Over the past several decades, adenocarcinoma of the lung has been increasing as a fraction of all lung cancer. Examination of the available evidence led the 2014 Report of the Surgeon General to conclude that the increases in the rates of adenocarcinoma among smokers in the U.S. were a result of changes in cigarette design and composition over the past 6 decades. While a causal link to design and composition changes as a whole is clear, the changes that have been implemented over the past several decades are not uniformly applied across all cigarette brands in the current market, raising questions about differences in risks among users of different cigarette brands. Recognition of the increased risks resulting from design and composition changes offers a corollary opportunity to reduce current disease risks by identifying and regulating the specific compositional and design changes that produced the increase in risk. PMID:25036935

  7. Choroidal and cutaneous metastasis from gastric adenocarcinoma.

    PubMed

    Kawai, Shoichiro; Nishida, Tsutomu; Hayashi, Yoshito; Ezaki, Hisao; Yamada, Takuya; Shinzaki, Shinichiro; Miyazaki, Masanori; Nakai, Kei; Yakushijin, Takayuki; Watabe, Kenji; Iijima, Hideki; Tsujii, Masahiko; Nishida, Kohji; Takehara, Tetsuo

    2013-03-01

    Choroidal or cutaneous metastasis of gastric cancer is rare. Gastrointestinal cancer was found in only 4% in patients with uveal metastasis. Choroidal metastasis from gastric cancer was reported in two cases in earlier literature. The frequency of gastric cancer as a primary lesion was 6% in cutaneous metastasis of men, and cutaneous metastasis occurs in 0.8% of all gastric cancers. We report a patient with gastric adenocarcinoma who presented with visual disorder in his left eye and skin pain on his head as his initial symptoms. These symptoms were diagnosed to be caused by choroidal and cutaneous metastasis of gastric adenocarcinoma. Two cycles of chemotherapy consisted of oral S-1 and intravenous cisplatin (SPIRITS regimen); this was markedly effective to reduce the primary gastric lesion and almost all the metastatic lesions. PMID:23538460

  8. Adenocarcinoma associated with tail gut cyst

    PubMed Central

    Wise, Susannah; Maloney-Patel, Nell; Rezac, Craig; Poplin, Elizabeth

    2013-01-01

    Primary adenocarcinomas of the presacral (retrorectal) space are rare. The diagnosis is usually delayed because of non-specific symptoms, and is made after a biopsy or surgery. These carcinomas arise from cystic lesions developing from remnants of the embryological postanal gut containing mucous-secreting epithelium, known as tail gut cysts. The potential for infection, perianal fistulas and most importantly, malignant change warrants an early complete surgical resection. From an oncologist’s perspective, the management of these carcinomas has varied, and has included adjuvant chemotherapy and/or radiation therapy. We describe here a rare case of adenocarcinoma associated with a tail gut cyst that was discovered incidentally and resected by a posterior approach (Kraske procedure). The patient has had clinical and periodic radiologic surveillance without any evidence of cancer recurrence for over a year and a half. PMID:23450681

  9. Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis.

    PubMed

    Masri, Selma; Papagiannakopoulos, Thales; Kinouchi, Kenichiro; Liu, Yu; Cervantes, Marlene; Baldi, Pierre; Jacks, Tyler; Sassone-Corsi, Paolo

    2016-05-01

    The circadian clock controls metabolic and physiological processes through finely tuned molecular mechanisms. The clock is remarkably plastic and adapts to exogenous "zeitgebers," such as light and nutrition. How a pathological condition in a given tissue influences systemic circadian homeostasis in other tissues remains an unanswered question of conceptual and biomedical importance. Here, we show that lung adenocarcinoma operates as an endogenous reorganizer of circadian metabolism. High-throughput transcriptomics and metabolomics revealed unique signatures of transcripts and metabolites cycling exclusively in livers of tumor-bearing mice. Remarkably, lung cancer has no effect on the core clock but rather reprograms hepatic metabolism through altered pro-inflammatory response via the STAT3-Socs3 pathway. This results in disruption of AKT, AMPK, and SREBP signaling, leading to altered insulin, glucose, and lipid metabolism. Thus, lung adenocarcinoma functions as a potent endogenous circadian organizer (ECO), which rewires the pathophysiological dimension of a distal tissue such as the liver. PAPERCLIP. PMID:27153497

  10. Lactation stage-dependent expression of transporters in rat whole mammary gland and primary mammary epithelial organoids.

    PubMed

    Gilchrist, Samuel E; Alcorn, Jane

    2010-04-01

    Since solute carrier (SLC) and ATP-binding cassette (ABC) transporters play pivotal roles in the transport of both nutrients and drugs into breast milk, drug-nutrient transport interactions at the lactating mammary gland are possible. Our purpose was to characterize lactation stage-dependent changes in transporter expression in rat mammary gland and isolated mammary epithelial organoids (MEO) to provide additional insight for the safe use of maternal medications during breastfeeding. We used quantitative reverse transcription-polymerase chain reaction to assess the temporal expression patterns of SLC and ABC transporters in rat mammary gland and isolated MEO at different stages of lactation. In whole mammary gland five distinct patterns of expression emerged relative to late gestation: (i) decreasing throughout lactation (Mdr1a, Mdr1b, Mrp1, Octn2, Ent2, Ent3, Ncbt2, Mtx1); (ii) prominent increase in early lactation, which may remain elevated or decline with advancing lactation (Octn1, Cnt2, Cnt3, Ent1, Pept1, Pept2); (iii) constant but decreasing later in lactation (Octn3, Dmt1); (iv) increasing until mid-to-late lactation (Oct1, Cnt1); and (v) prominent increase late in lactation (Ncbt1). In isolated MEO (an enriched source of mammary epithelial cells) major differences in expression patterns were noted for Octn3, Ncbt1, and Mtx1, but otherwise were reasonably similar with the whole mammary gland. In conclusion our study augments existing data on transporter expression in the lactating mammary gland. These data should facilitate investigations into lactation-stage dependent changes in drug or nutrient milk-to-serum concentration ratios, the potential for drug- or disease-transporter interactions, and mechanistic studies of transporter function in the lactating mammary gland. PMID:19702690

  11. Appendiceal Adenocarcinoma Presenting as a Rectal Polyp

    PubMed Central

    Fitzgerald, Erin; Chen, Lilian; Guelrud, Moises; Allison, Harmony; Zuo, Tao; Suarez, Yvelisse; Yoo, James

    2016-01-01

    Appendiceal adenocarcinoma typically presents as an incidentally noted appendiceal mass, or with symptoms of right lower quadrant pain that can mimic appendicitis, but local involvement of adjacent organs is uncommon, particularly as the presenting sign. We report on a case of a primary appendiceal cancer initially diagnosed as a rectal polyp based on its appearance in the rectal lumen. The management of the patient was in keeping with standard practice for a rectal polyp, and the diagnosis of appendiceal adenocarcinoma was made intraoperatively. The operative strategy had to be adjusted due to this unexpected finding. Although there are published cases of appendiceal adenocarcinoma inducing intussusception and thus mimicking a cecal polyp, there are no reports in the literature describing invasion of the appendix through the rectal wall and thus mimicking a rectal polyp. The patient is a 75-year-old female who presented with spontaneous hematochezia and, on colonoscopy, was noted to have a rectal polyp that appeared to be located within a diverticulum. When endoscopic mucosal resection was not successful, she was referred to colorectal surgery for a low anterior resection. Preoperative imaging was notable for an enlarged appendix adjacent to the rectum. Intraoperatively, the appendix was found to be densely adherent to the right lateral rectal wall. An en bloc resection of the distal sigmoid colon, proximal rectum and appendix was performed, with pathology demonstrating appendiceal adenocarcinoma that invaded through the rectal wall. The prognosis in this type of malignancy weighs heavily on whether or not perforation and spread throughout the peritoneal cavity have occurred. In this unusual presentation, an en bloc resection is required for a complete resection and to minimize the risk of peritoneal spread. Unusual appearing polyps do not always originate from the bowel wall. Abnormal radiographic findings adjacent to an area of gastrointestinal pathology may

  12. Genetics and Biology of Pancreatic Ductal Adenocarcinoma.

    PubMed

    Dunne, Richard F; Hezel, Aram F

    2015-08-01

    Pancreatic ductal adenocarcinoma remains a clinical challenge. Thus far, enlightenment on the downstream activities of Kras, the tumor's unique metabolic needs, and how the stroma and immune system affect it have remained untranslated to the clinical practice. Given the numbers of diverse therapies in development and a growing knowledge about how to evaluate these systems preclinically and clinically, this is expected to change significantly and for the better over the next 5 years. PMID:26226899

  13. The update of prostatic ductal adenocarcinoma

    PubMed Central

    Liu, Tantan; Wang, Yingmei; Zhou, Ru; Li, Haiyang; Cheng, Hong

    2016-01-01

    Since initially described in 1967, prostatic ductal adenocarcinoma (PDA) has engendered a series of controversies on its origin, histological features, and biological behavior. Owing to the improvement of molecular biological technique, there are some updated findings on the characteristics of PDA. In the current review, we will mainly analyze its origin, clinical manifestations, morphological features, differential diagnosis, immunophenotype and molecular genetics, with the purpose of enhancing recognition of this tumor and making a correct diagnosis and treatment choice. PMID:27041926

  14. Do Dogs Provide Information Helpfully?

    PubMed Central

    Piotti, Patrizia; Kaminski, Juliane

    2016-01-01

    Dogs are particularly skilful during communicative interactions with humans. Dogs’ abilities to use human communicative cues in cooperative contexts outcompete those of other species, and might be the result of selection pressures during domestication. Dogs also produce signals to direct the attention of humans towards outside entities, a behaviour often referred to as showing behaviour. This showing behaviour in dogs is thought to be something dogs use intentionally and referentially. However, there is currently no evidence that dogs communicate helpfully, i.e. to inform an ignorant human about a target that is of interest to the human but not to the dog. Communicating with a helpful motive is particularly interesting because it might suggest that dogs understand the human’s goals and need for information. In study 1, we assessed whether dogs would abandon an object that they find interesting in favour of an object useful for their human partner, a random novel distractor, or an empty container. Results showed that it was mainly self-interest that was driving the dogs’ behaviour. The dogs mainly directed their behaviour towards the object they had an interest in, but dogs were more persistent when showing the object relevant to the human, suggesting that to some extent they took the humans interest into account. Another possibility is that dogs’ behaviour was driven by an egocentric motivation to interact with novel targets and that the dogs’ neophila might have masked their helpful tendencies. Therefore, in study 2 the dogs had initial access to both objects, and were expected to indicate only one (relevant or distractor). The human partner interacted with the dog using vocal communication in half of the trials, and remaining silent in the other half. Dogs from both experimental groups, i.e. indicating the relevant object or indicating the distractor, established joint attention with the human. However, the human’s vocal communication and the presence

  15. Carcinogenesis of Pancreatic Adenocarcinoma: Precursor Lesions

    PubMed Central

    Gnoni, Antonio; Licchetta, Antonella; Scarpa, Aldo; Azzariti, Amalia; Brunetti, Anna Elisabetta; Simone, Gianni; Nardulli, Patrizia; Santini, Daniele; Aieta, Michele; Delcuratolo, Sabina; Silvestris, Nicola

    2013-01-01

    Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy. PMID:24084722

  16. Comprehensive molecular profiling of lung adenocarcinoma.

    PubMed

    2014-07-31

    Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. PMID:25079552

  17. Predictors of Survival in Sinonasal Adenocarcinoma.

    PubMed

    Chen, Michelle M; Roman, Sanziana A; Sosa, Julie A; Judson, Benjamin L

    2015-06-01

    Objectives To identify factors associated with disease-specific survival (DSS) in intestinal and nonintestinal sinonasal adenocarcinoma. Design Retrospective review. Setting Surveillance Epidemiology and End Results database. Participants Adult patients with sinonasal adenocarcinoma. Main Outcome Measures DSS. Results We identified 325 patients; of these, 300 had the nonintestinal type and 25 had intestinal type histologies. The 5-year DSS rates for patients who had no treatment, radiation (RT), surgery, and surgery and postoperative RT were 42.5, 46.1, 85.6, and 72.6%, respectively (log-rank test; p < 0.001). Black race, age ≥ 75 years, paranasal sinus involvement, and high grade were independently associated with decreased DSS. Compared with RT, surgery (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.15-0.77), and adjuvant RT (HR: 0.47; 95% CI, 0.26-0.86) were associated with improved DSS. Conclusions There is no difference in prognosis between intestinal and nonintestinal subtypes of sinonasal adenocarcinoma. Treatment with surgery alone or adjuvant RT is associated with a more favorable prognosis. PMID:26225303

  18. Colorectal Adenocarcinoma Metastasis to the Tongue

    PubMed Central

    Gill, Kurren S.; Frattali, Mark A.

    2015-01-01

    This case presentation examines a rare clinical entity: colorectal adenocarcinoma (CRC) metastasis to the tongue. CRC is among the least common tumors to metastasize to the oral cavity. Objectives for this case report are to (1) maintain a high index of suspicion for oral cavity tumors representing metastatic disease, (2) consider appropriate surgical and adjunctive interventions, and (3) recognize the significance of identifying the primary tumor via immunohistochemical staining. We present a case of a 57-year-old male with a history of stage IV rectal adenocarcinoma metastatic to the lung who presented to our clinic with a painful mass of the right lateral tongue that he noticed one month before. MRI of the neck revealed a mass involving the anterior two-thirds of the right tongue with irregular margins and an ipsilateral enlarged right jugulodigastric lymph node. The patient underwent right partial glossectomy with primary reconstruction and right modified radical neck dissection. Pathology confirmed poorly differentiated adenocarcinoma consistent with a colorectal primary with lymphovascular and perineural invasion. The tumor was staged as T2N1, and the patient was referred for chemoradiation. In this report, we discuss the presentation, diagnosis, and treatment of this uncommon disease, with a thorough review of the world literature. PMID:26759728

  19. Targeting chemokine pathways in esophageal adenocarcinoma

    PubMed Central

    Shrivastava, Makardhwaj S; Hussain, Zulfiqar; Giricz, Orsolya; Shenoy, Niraj; Polineni, Rahul; Maitra, Anirban; Verma, Amit

    2014-01-01

    Esophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US and needs newer therapeutic and diagnostic strategies. Chronic inflammation plays a role in the pathogenesis of EAC and contributes to the dysplastic conversion of normal esophageal epithelium to Barrett's esophagus and frank adenocarcinoma. Chemokines play important roles in mediating inflammation and recent evidence implicates these ligands and their receptors in the development and spread of various tumors. We demonstrated that the chemokines IL8, CXCL1 and CXCL3 are significantly overexpressed during esophageal carcinogenesis and accompanied by amplification and demethylation of the chr4q21 gene locus. We also demonstrated that IL8 levels can be detected in serum of patients with EAC and can serve as potential biomarkers. We now demonstrate that inhibition of IL8 receptor, CXCR2, leads to decreased invasiveness of esophageal adenocarcinoma derived cells without affecting cellular proliferation. Taken together, these studies reveal the important roles that chemokines play in development of esophageal cancer and demonstrate that these pathways can serve as potential therapeutic targets. PMID:25485576

  20. Immunohistochemical Profile for Unknown Primary Adenocarcinoma

    PubMed Central

    Hashimoto, Kenji; Sasajima, Yuko; Ando, Masashi; Yonemori, Kan; Hirakawa, Akihiro; Furuta, Koh; Tsuda, Hitoshi; Fujiwara, Yasuhiro

    2012-01-01

    Background Development of tailored treatment based on immunohistochemical profiles (IPs) of tumors for cancers of unknown primary is needed. Methodology/Principal Findings We developed an algorithm based on primary known adenocarcinoma for testing sensitivity and specificity. Formalin-fixed paraffin-embedded tissue samples from 71 patients of unfavorable subsets of unknown primary adenocarcinoma were obtained. We examined 15 molecular markers using the algorithm incorporating these IPs and classified the tumours into 9 subsets based on the primary tumour site. The sensitivity and specificity of this algorithm were 80.3% and 97.6%, respectively. Apparent primary sites were lung in 17 patients, digestive organs in 13, gynecological organs in 9, prostate in 7, liver or kidney in 6, breast in 4, urothelial organ in 2, biliary tract and pancreatic profile in none, and unclassified in 13. The response rate to chemotherapy was highest for the gynecological IPs. Patients with gynecological or lung cancer IPs had longer median progression-free survival than those with others: 11.2 months for gynecological IPs (p<0.001) and 6.8 months for lung IPs (p = 0.05). Lung, digestive, prostate, and gynecological profiles were associated with significantly longer median survival time than the other profiles. Multivariate analysis confirmed that the IPs were independent prognostic factors for survival. Conclusions/Significance The IPs identified in this study can be used to further stratify patient prognosis for unfavorable subsets of unknown primary adenocarcinoma. PMID:22299055

  1. Quantitative PCR marker genes for endometrial adenocarcinoma.

    PubMed

    Kölbl, Alexandra C; Victor, Lisa-Marie; Birk, Amelie E; Jeschke, Udo; Andergassen, Ulrich

    2016-09-01

    Endometrial adenocarcinoma is a common malignancy in women worldwide, with formation of remote metastasis occurring following oncological treatment. Circulating tumor cells (CTCs) are regarded to be the origin of haematogenous metastasis formation. The present study aimed to identify suitable marker genes using a quantitative polymerase chain reaction (qPCR) approach to detect CTCs from blood samples of patients with endometrial carcinoma. Therefore, RNA was isolated from endometrial adenocarcinoma cell lines and from healthy endometrial tissue and reverse transcribed to cDNA, which was then used in qPCR on a number of marker genes. Cytokeratin 19 and claudin 4 were identified as suitable marker genes for CTCs in endometrial adenocarcinoma, due to their high expression in the majority of the cell lines investigated. The expression values of the genes examined varied widely between the different cell lines, which is similar to the variation in the patient samples. Therefore, the necessity for a set of genes for CTC detection and not one single marker gene is demonstrated. qPCR is a fast, cost‑efficient and easy to perform technique, which may be used in the detection of CTCs. Investigation of the occurrence of CTCs in cancer patients would aid in the prevention of metastasis and thereby refine treatment. PMID:27431566

  2. Predictors of Survival in Sinonasal Adenocarcinoma

    PubMed Central

    Chen, Michelle M.; Roman, Sanziana A.; Sosa, Julie A.; Judson, Benjamin L.

    2015-01-01

    Objectives To identify factors associated with disease-specific survival (DSS) in intestinal and nonintestinal sinonasal adenocarcinoma. Design Retrospective review. Setting Surveillance Epidemiology and End Results database. Participants Adult patients with sinonasal adenocarcinoma. Main Outcome Measures DSS. Results We identified 325 patients; of these, 300 had the nonintestinal type and 25 had intestinal type histologies. The 5-year DSS rates for patients who had no treatment, radiation (RT), surgery, and surgery and postoperative RT were 42.5, 46.1, 85.6, and 72.6%, respectively (log-rank test; p < 0.001). Black race, age ≥ 75 years, paranasal sinus involvement, and high grade were independently associated with decreased DSS. Compared with RT, surgery (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.15–0.77), and adjuvant RT (HR: 0.47; 95% CI, 0.26–0.86) were associated with improved DSS. Conclusions There is no difference in prognosis between intestinal and nonintestinal subtypes of sinonasal adenocarcinoma. Treatment with surgery alone or adjuvant RT is associated with a more favorable prognosis. PMID:26225303

  3. Comprehensive molecular profiling of lung adenocarcinoma

    PubMed Central

    2014-01-01

    Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. PMID:25079552

  4. [Ductal adenocarcinoma and unusual differential diagnosis].

    PubMed

    Haage, P; Schwartz, C A; Scharwächter, C

    2016-04-01

    Ductal pancreatic adenocarcinoma is by far the most common solid tumor of the pancreas. It has a very poor prognosis, especially in the more advanced stages which are no longer locally confined. Due to mostly unspecific symptoms, imaging is key in the diagnostic process. Because of the widespread use of imaging techniques, incidental findings are to a greater extent discovered in the pancreas, which subsequently entail further work-up. Ductal pancreatic adenocarcinoma can be mimicked by a large number of different lesions, such as anatomical variants, peripancreatic structures and tumors, rarer primary solid pancreatic tumors, cystic tumors, metastases or different variants of pancreatitis. Additionally, a number of precursor lesions can be differentiated. The correct classification is thus important as an early diagnosis of ductal pancreatic adenocarcinoma is relevant for the prognosis and because the possibly avoidable treatment is very invasive. All major imaging techniques are principally suitable for pancreatic imaging. In addition to sonography of the abdomen, usually the baseline diagnostic tool, computed tomography (CT) with its superior spatial resolution, magnetic resonance imaging (MRI) with its good soft tissue differentiation capabilities, possibly in combination with MR cholangiopancreatography (MRCP), endosonography with its extraordinary spatial resolution, conceivably with additional endoscopic retrograde CP or the option of direct biopsy and finally positron emission tomography CT (PET-CT) as a molecular imaging tool are all particularly useful modalities. The various techniques all have its advantages and disadvantages; depending on the individual situation they may need to be combined. PMID:27000276

  5. Gene expression profiling in sinonasal adenocarcinoma

    PubMed Central

    2009-01-01

    Background Sinonasal adenocarcinomas are uncommon tumors which develop in the ethmoid sinus after exposure to wood dust. Although the etiology of these tumors is well defined, very little is known about their molecular basis and no diagnostic tool exists for their early detection in high-risk workers. Methods To identify genes involved in this disease, we performed gene expression profiling using cancer-dedicated microarrays, on nine matched samples of sinonasal adenocarcinomas and non-tumor sinusal tissue. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors. Results Among the genes with significant differential expression we selected LGALS4, ACS5, CLU, SRI and CCT5 for further exploration. The overexpression of LGALS4, ACS5, SRI, CCT5 and the downregulation of CLU were confirmed by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4 (Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins: LGALS4 was highly up-regulated, particularly in the most differentiated tumors, while CLU was lost in all tumors. The expression of ACS5, was more heterogeneous and no correlation was observed with the tumor type. Conclusion Within our microarray study in sinonasal adenocarcinoma we identified two proteins, LGALS4 and CLU, that were significantly differentially expressed in tumors compared to normal tissue. A further evaluation on a new set of tissues, including precancerous stages and low grade tumors, is necessary to evaluate the possibility of using them as diagnostic markers. PMID:19903339

  6. Using dogs for tiger conservation and research.

    PubMed

    Kerley, Linda L

    2010-12-01

    This paper is a review of the history, development and efficacy of using dogs in wildlife studies and considers the use of dogs in the research and conservation of wild tigers (Panthera tigris Linnaeus, 1758). Using scat detection dogs, scent-matching dogs, law enforcement detection dogs and protection dogs are proven methods that can be effectively used on tigers. These methods all take advantage of the dog's extremely evolved sense of smell that allows them to detect animals or animal byproducts (often the focus of tiger studies). Dogs can be trained to communicate this information to their handlers. PMID:21392356

  7. Investigation of the local expression of the relaxin system in canine mammary tumours.

    PubMed

    Lamp, O; Honscha, K U; Jakob, J; Lamp, J; Schweizer, S; Reischauer, A; Gottschalk, J; Hahn, A; Ebert, M; Rothemund, S; Blaschzik, S; Einspanier, A

    2009-07-01

    While mammary tumours are the main reasons of death in bitches, early detection of tumours and metastases is crucial for survival of affected dogs. Invasiveness and angiogenesis, which are important processes of tumour growth and spreading, require connective tissue remodelling. This process is dominantly mediated by matrix metalloproteinases (MMP), which are well known to be positively regulated by relaxin (RLX) in various tissues, including human breast cancer. So far, the presence of RLX and its receptor RXFP-1 as well as their linkage with MMP in canine mammary tumours (CMT) is completely unknown. In the first part of the present study, concentrations of RLX, oestradiol and progesterone from plasma samples of bitches with CMT were compared with clinical and survival data to investigate the predictive value of these hormones. In the second part, the expressions of RLX, RXFP-1 and MMP-2, -9 and -13 were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in 31 CMT samples. Finally, relationships of systemic plasma RLX or locally expressed RLX with expression of MMP in CMT were analyzed for the first time. Comparison of hormone concentrations in 93 bitches in terms of benign or malignant nature of the CMT, lung metastases, recidivation and 12-month survival discovered no significances. The expressions of RLX, RXFP-1 and MMP were independent from plasma RLX, but expressions of local RLX and RXFP-1 showed a strong correlation (p = 0.00004, r = 0.671) as well as RXFP-1 and MMP-2 (p = 0.009, r = 0.463), indicating a possible significant role of the locally produced RLX in CMT pathogenesis as an inducer of connective tissue remodelling. PMID:19754574

  8. Solitary Psoas Muscle Metastasis of Gastroesphageal Junction Adenocarcinoma

    PubMed Central

    Azadeh, Payam; Yaghobi Joybari, Ali; Sarbaz, Samaneh; Ghiasi, Hosein Ali; Farasatinasab, Maryam

    2016-01-01

    Metastasis of gastroesphageal junction (GEJ) adenocarcinoma in skeletal muscle is rare and primary sites for skeletal muscle metastases are usually lung, renal and colorectal cancer. We have encountered with the first case report of solitary psoas muscle metastasis of GEJ adenocarcinoma. Here we describe a 65 years old man was diagnosed with GEJ adenocarcinoma in Gastroenterology Department, Imam Hussein Hospital, Tehran, Iran in February 2014. We were not able to use PET techniques due to lack of access. Staging CT scans demonstrated a small mass lateral to right psoas muscle. A CT-guided core needle biopsy of right psoas muscle was performed that supported a diagnosis of adenocarcinoma consistent with primary adenocarcinoma of the GEJ. Distant metastasis to skeletal muscle rarely occurs in patients with GEJ adenocarcinoma, but heightened awareness to these soft tissue lesions is warranted. CT or MR imaging could show findings suggestive of metastatic disease, although PET is preferable modality. PMID:26870148

  9. Metastatic lung adenocarcinoma to the bladder: A case report

    PubMed Central

    YE, HAI-JUN; MA, JIAN; LIU, YING-JIE; YE, XIAO-FEI; ZHANG, LI-WANG; LI, JIN-GE

    2015-01-01

    Urothelial cancer is the most frequently diagnosed type of malignant tumor in the bladder, of which primary adenocarcinoma accounts for a small percentage. Secondary malignancies, in particular metastatic adenocarcinoma from the lung, are exceedingly rare, with only six cases previously reported in the literature. The present study describes the case of a 71-year-old Chinese male patient with known lung cancer for >2 years, who was diagnosed with metastatic adenocarcinoma to the bladder. The histopathological characteristics and immunohistochemical features of the patient are reported. It was proposed that pathologists should consider the possibility of metastatic adenocarcinoma from the lung, rather than assume a diagnosis of primary adenocarcinoma of the bladder or direct invasion of adenocarcinoma from the surrounding organs. Furthermore, it is essential to determine the medical history of each patient and observe the immunohistochemical features of all tumors prior to diagnosis. PMID:26622730

  10. Developmental biology: cell fate in the mammary gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most breast cancers have their origin in the luminal epithelial cells of the mammary gland. Defining how a master regulator controls the development of this cell lineage could provide important hints about why this should be. ...

  11. Metabolic adaptations in goat mammary tissue during pregnancy and lactation.

    PubMed

    Wilde, C J; Henderson, A J; Knight, C H

    1986-01-01

    Metabolic adaptations of goat mammary tissue during pregnancy and lactation were monitored in serial biopsies of the tissue. Changes in the synthetic capacity of secretory cells were studied by combining measurements of enzyme activities with short-term culture of mammary explants to measure lactose, casein and total protein synthesis. By these criteria, the main phase of mammary differentiation began in late pregnancy and was essentially complete by Week 5 of lactation, coinciding with the achievement of peak milk yield. While milk yield declined after Week 5, the activities of key enzymes expressed per mg DNA and the rates of lactose and casein synthesis in mammary explants were maintained over a considerable period. The results suggest that changes in the synthetic capacity of epithelial cells may account for much of the rise in milk yield in early lactation, but are not responsible for the declining phase of milk production characteristic of lactation in ruminants. PMID:2868125

  12. Lessons Learned from Mouse Mammary Tumor Virus in Animal Models.

    PubMed

    Dudley, Jaquelin P; Golovkina, Tatyana V; Ross, Susan R

    2016-03-31

    Mouse mammary tumor virus (MMTV), which was discovered as a milk-transmitted, infectious, cancer-inducing agent in the 1930s, has been used as an animal model for the study of retroviral infection and transmission, antiviral immune responses, and breast cancer and lymphoma biology. The main target cells for MMTV infection in vivo are cells of the immune system and mammary epithelial cells. Although the host mounts an immune response to the virus, MMTV has evolved multiple means of evading this response. MMTV causes mammary tumors when the provirus integrates into the mammary epithelial and lymphoid cell genome during viral replication and thereby activates cellular oncogene expression. Thus, tumor induction is a by-product of the infection cycle. A number of important oncogenes have been discovered by carrying out MMTV integration site analysis, some of which may play a role in human breast cancer. PMID:27034391

  13. Primary Adenocarcinoma of an Ileostomy in Crohn's Disease

    PubMed Central

    Prasad, Meena A.; Lo, Amy; Bellaguarda, Emanuelle; Strong, Scott; Hanauer, Stephen B.

    2016-01-01

    Although Crohn's disease has been associated with an increased risk of small bowel adenocarcinoma, primary adenocarcinoma arising from an ileostomy is a complication that has been rarely documented in Crohn's disease. Chronic small bowel inflammation may lead to development of malignancy through the dysplasia-carcinoma sequence. We report a case of a 61-year-old woman with Crohn's ileocolitis diagnosed with a primary adenocarcinoma at the ileostomy with metastases to the liver 47 years after proctocolectomy, and review the literature.

  14. Mammary tumors induce select cognitive impairments.

    PubMed

    Pyter, Leah M; Cochrane, Sally F; Ouwenga, Rebecca L; Patel, Priyesh N; Pineros, Vanessa; Prendergast, Brian J

    2010-08-01

    Cancer, in addition to many other chronic diseases, is associated with serious and problematic behavioral symptoms, including cognitive impairments. In humans, various factors likely contribute to cancer-associated cognitive deficits including disease awareness and chemotherapy; however, the endogenous biological factors arising from tumor development may also play a causal role. In the present study, rats with mammary tumors exhibited impaired spatial reference memory on a radial arm maze and amnesia for familiar objects in an object recognition memory test. In contrast, their performance in the Morris water maze and in fear conditioning tests was comparable to that of controls. These select cognitive impairments were accompanied by elevations in hippocampal interleukin-1beta mRNA expression, but were not associated with decreases in hippocampal brain-derived neurotrophic factor gene expression. Together the results indicate that peripheral tumors alone are sufficient to induce increases in hippocampal cytokine expression and select deficits in hippocampal-dependent memory tasks. PMID:20188817

  15. Collection Development "Dog Care & Training": The Well-Behaved Dog

    ERIC Educational Resources Information Center

    Alpi, Kristine M.; Sherman, Barbara L.

    2008-01-01

    Dogs are indeed people's best friends. A majority of owners report that their dog is a "member of the family," and that acceptable canine behavior and optimal care are high priorities for them. The human-animal bond, the close connection between people and their pets, is forged by positive interactions, but unacceptable canine behaviors that…

  16. Chemoprevention of Radiation Induced Rat Mammary Neoplasms

    NASA Technical Reports Server (NTRS)

    Huso, David L.

    1999-01-01

    Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable

  17. Radiogenic neoplasia in thyroid and mammary clonogens

    SciTech Connect

    Clifton, K.H.

    1991-05-31

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process.

  18. Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli

    PubMed Central

    Blum, Shlomo E.; Heller, Elimelech D.; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

    2015-01-01

    Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study

  19. Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli.

    PubMed

    Blum, Shlomo E; Heller, Elimelech D; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

    2015-01-01

    Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study

  20. COX-2 expression in canine and feline invasive mammary carcinomas: correlation with clinicopathological features and prognostic molecular markers.

    PubMed

    Millanta, F; Citi, S; Della Santa, D; Porciani, M; Poli, A

    2006-07-01

    Cyclooxygenase (COX)-2 is an inducible enzyme linked to tumor growth and angiogenesis. Its expression occurs in a wide range of preneoplastic and neoplastic conditions in humans, including colon and breast carcinomas. We evaluated the role of COX-2 as a mediator of angiogenesis in feline and canine invasive carcinomas (IMCs) and its role as a prognostic indicator. COX-2 expression was assessed in neoplastic samples and healthy mammary glands by immunohistochemistry, and related to the following clinicopathological parameters: age, tumor size, histologic type, tumor grading, vessel invasion, estrogen (ER) and progesterone receptor (PR) status, Ki-67, HER-2 overexpression, microvessel density (MVD), VEGF expression and overall survival (OS). In both species, COX-2 immunoreactivity was not observed in healthy tissues, whereas 96% of feline and 100% of canine invasive carcinomas scored positive. In queens, COX-2 overexpression was significantly correlated to ER-negative status (p=0.04) and to increased PR (p=0.038) expression, and angiogenesis assessed by VEGF expression (p=0.002). In bitches an increased COX-2 expression was significantly correlated to HER-2 overexpression (p=0.013) and to tumor dedifferentiation (p=0.03). In both species increased levels of COX-2 were correlated to poorer prognosis (p=0.03 in dogs and p=0.002 in cats). COX-2 is expressed in mammary tissues during tumorigenesis and its expression is associated with a poorer prognosis in bitches and queens. The correlation of COX-2 expression and angiogenesis provides support for a potential role of COX-2 inhibitors for the prevention and the treatment of feline IMCs via their anti-angiogenic properties. In the canine species, moreover, COX-2 may be important for mediating HER-2 induced mammary tumors. PMID:16538539

  1. [Fighting dogs--dangerous dogs: legal situation in Bavaria].

    PubMed

    Breitsamer, F

    2001-03-01

    A report is given on eight years of experience with the Bavarian legal regulation for the protection against dangerous dogs of 10.7.1992. The implementation of the regulation was a success. Since then only two cases of biting accidents are reported. In one case the dogs were euthanatized, in the other case they were taken away and given to other owners. The advantages of the regulation are seen in the increased responsibility of the dog owner who has to give proof of the peaceful character of his dog in form of an expert testimony. This lowers the administration costs and has revealed a preventive effect, the dog owners are looking more carefully after their animals to avoid any security problems. PMID:11314462

  2. Downregulation of transforming growth factor β (TGFβ) and latent TGFβ binding protein (LTBP)-4 expression in late stage canine mammary tumours.

    PubMed

    Klopfleisch, R; Schütze, M; Gruber, A D

    2010-12-01

    Although canine mammary tumours (CMT) are the most common malignant tumours in bitches the pathogenesis is far from understood. To analyse the role of the transforming growth factor β (TGFβ) family in the carcinogenesis of CMT, relative mRNA and protein expression of TGFβ-1, -2 and -3, TGFβ receptor (TGFβR)-1 and -3, latent TGFβ-binding protein (LTBP)-1, -3 and -4, and oestrogen receptor α in CMT were quantified. mRNA expression concentrations were measured in laser-microdissected tissue samples of mammary adenomas, carcinomas and their lymph node metastases and normalised to the non-neoplastic mammary gland of the same dog. Carcinomas and metastases had significantly decreased expression levels of TGFβ-3, TGFβR-3 and LTBP-4, but increased LTBP-1 expression when compared to non-neoplastic glands or adenomas. Decreased TGFβ and LTBP-4 expression were confirmed immunohistochemically. The data suggested that loss of TGFβ-3 and LTBP-4 may have growth-stimulatory effects in late-stage tumours, and loss of their expression, together with reduced TGFβR-3 expression, may be associated with increased proliferative activity of CMT similar to findings in human breast cancer. PMID:19836277

  3. A Comparison of Fresh Frozen vs. Formalin-Fixed, Paraffin-Embedded Specimens of Canine Mammary Tumors via Branched-DNA Assay.

    PubMed

    Lüder Ripoli, Florenza; Mohr, Annika; Conradine Hammer, Susanne; Willenbrock, Saskia; Hewicker-Trautwein, Marion; Hennecke, Silvia; Murua Escobar, Hugo; Nolte, Ingo

    2016-01-01

    Mammary neoplasms are the tumors most affecting female dogs and women. Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable source of archived biological material. Fresh frozen (FF) tissue is considered ideal for gene expression analysis. However, strategies based on FFPE material offer several advantages. Branched-DNA assays permit a reliable and fast workflow when analyzing gene expression. The aim of this study was to assess the comparability of the branched-DNA assay when analyzing certain gene expression patterns between FF and FFPE samples in canine mammary tumors. RNA was isolated from 109 FFPE samples and from 93 FF samples of different canine mammary tissues. Sixteen (16) target genes (Tp53; Myc; HMGA1; Pik3ca; Mcl1; MAPK3; FOXO3; PTEN; GATA4; PFDN5; HMGB1; MAPK1; BRCA2; BRCA1; HMGA2; and Her2) were analyzed via branched-DNA assay (b-DNA). ACTB, GAPDH, and HPRT1 were used as data normalizers. Overall, the relative gene expression of the two different origins of samples showed an agreement of 63%. Still, care should be taken, as FFPE specimens showed lower expression of the analyzed targets when compared to FF samples. The fact that the gene expression in FFPE proved to be lower than in FF specimens is likely to have been caused by the effect of storage time. ACTB had the best performance as a data normalizer. PMID:27187374

  4. A Comparison of Fresh Frozen vs. Formalin-Fixed, Paraffin-Embedded Specimens of Canine Mammary Tumors via Branched-DNA Assay

    PubMed Central

    Lüder Ripoli, Florenza; Mohr, Annika; Conradine Hammer, Susanne; Willenbrock, Saskia; Hewicker-Trautwein, Marion; Hennecke, Silvia; Murua Escobar, Hugo; Nolte, Ingo

    2016-01-01

    Mammary neoplasms are the tumors most affecting female dogs and women. Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable source of archived biological material. Fresh frozen (FF) tissue is considered ideal for gene expression analysis. However, strategies based on FFPE material offer several advantages. Branched-DNA assays permit a reliable and fast workflow when analyzing gene expression. The aim of this study was to assess the comparability of the branched-DNA assay when analyzing certain gene expression patterns between FF and FFPE samples in canine mammary tumors. RNA was isolated from 109 FFPE samples and from 93 FF samples of different canine mammary tissues. Sixteen (16) target genes (Tp53; Myc; HMGA1; Pik3ca; Mcl1; MAPK3; FOXO3; PTEN; GATA4; PFDN5; HMGB1; MAPK1; BRCA2; BRCA1; HMGA2; and Her2) were analyzed via branched-DNA assay (b-DNA). ACTB, GAPDH, and HPRT1 were used as data normalizers. Overall, the relative gene expression of the two different origins of samples showed an agreement of 63%. Still, care should be taken, as FFPE specimens showed lower expression of the analyzed targets when compared to FF samples. The fact that the gene expression in FFPE proved to be lower than in FF specimens is likely to have been caused by the effect of storage time. ACTB had the best performance as a data normalizer. PMID:27187374

  5. Profile of Steroid Receptors and Increased Aromatase Immunoexpression in Canine Inflammatory Mammary Cancer as a Potential Therapeutic Target.

    PubMed

    De Andrés, P J; Cáceres, S; Clemente, M; Pérez-Alenza, M D; Illera, J C; Peña, L

    2016-04-01

    Canine inflammatory mammary cancer (IMC) has been proposed as a model for the study of human inflammatory breast cancer (IBC). The aims of this study were to compare the immunohistochemical expression of aromatase (Arom) and several hormone receptors [estrogen receptor α (ERα), estrogen receptor β (ERβ), progesterone receptor (PR) and androgen receptor (AR)], in 21 IMC cases vs 19 non-IMC; and to study the possible effect of letrozole on canine IMC and human inflammatory breast cancer (IBC) in vitro using IPC-366 and SUM-149 cell lines. Significant elevations of the means of Arom Total Score (TS), ERβ TS and PR TS were found in the IMC group (p = 0.025, p = 0.038 and p = 0.037, respectively). Secondary IMC tumours expressed higher levels of Arom than primary IMC (p = 0.029). Non-IMC PR- tumours contained higher levels of Arom than non-IMC PR+ tumours (p = 0.007). After the addition of letrozole, the number of IMC and IBC cells dropped drastically. The overexpression of Arom found and the results obtained in vitro further support canine IMC as a model for the study of IBC and future approaches to the treatment of dogs with mammary cancer, and especially IMC, using Arom inhibitors. PMID:26899138

  6. Effect of ovariohysterectomy in bitches with mammary neoplasms.

    PubMed

    Morris, J S; Dobson, J M; Bostock, D E; O'Farrell, E

    1998-06-13

    Ninety bitches with mammary tumours were studied for two years after the surgical removal of the primary tumour(s). Twenty-nine of the bitches had been spayed before the development of the mammary tumour, 22 were spayed when the tumours were removed and 39 were left entire. Fifty-eight of the bitches (64 per cent) had benign tumours and, of these, 15 (26 per cent) developed a new mammary tumour within two years, irrespective of whether the bitch was spayed. The other 32 bitches had malignant tumours which were grouped into 'invasive' and 'well defined' carcinomas. Sixty-three per cent of the spayed bitches and 57 per cent of the entire bitches, with invasive carcinoma were dead within two years of surgery as a result of their mammary tumours. For those with well defined carcinomas the tumour-related death rates were 18 per cent and 33 per cent respectively for the spayed and entire bitches. These findings suggest that ovariohysterectomy when mammary tumours are removed does not have a significant effect on the progression of malignant disease, and that about one in four bitches with a benign mammary tumour is likely to develop a further tumour in another gland. PMID:9670443

  7. Technical note: Isolation and characterization of porcine mammary epithelial cells.

    PubMed

    Dahanayaka, S; Rezaei, R; Porter, W W; Johnson, G A; Burghardt, R C; Bazer, F W; Hou, Y Q; Wu, Z L; Wu, G

    2015-11-01

    Within the mammary gland, functional synthesis of milk is performed by its epithelial (alveolar) cells. The availability of a stable mammary epithelial cell line is essential for biochemical studies to elucidate cellular and molecular mechanisms responsible for nutritional regulation of lactation. Therefore, porcine mammary epithelial cells (PMEC) were isolated from mammary glands of a 9-mo-old nonpregnant and nonlactating gilt and cultured to establish a nonimmortalized cell line. These cells were characterized by expression of cytokeratin-18 (an intermediate filament specific for epithelial cells), β-casein (a specific marker for mammary epithelial cells), and α-lactalbumin. In culture, the PMEC doubled in number every 24 h and maintained a cobblestone morphology, typical for cultured epithelial cells, for at least 15 passages. Addition of 0.2 to 2 μg/mL prolactin to culture medium for 3 d induced the production of β-casein and α-lactalbumin by PMEC in a dose-dependent manner. Thus, we have successfully developed a useful PMEC line for future studies of cellular and molecular regulation of milk synthesis by mammary epithelial cells of the sow. PMID:26641038

  8. TCDD exposure disrupts mammary epithelial cell differentiation and function

    PubMed Central

    Collins, Loretta L.; Lew, Betina J.; Lawrence, B. Paige

    2011-01-01

    Mammary gland growth and differentiation during pregnancy is a developmental process that is sensitive to the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a widespread environmental contaminant and a potent ligand for the aryl hydrocarbon receptor (AhR). We demonstrate reduced β-casein protein induction in mouse mammary glands and in cultured SCp2 mammary epithelial cells following exposure to TCDD. SCp2 cells exposed to TCDD also show reduced cell clustering and less alveolar-like structure formation. SCp2 cells express transcriptionally active AhR, and exposure to TCDD induces expression of the AhR target gene CYP1B1. Exposure to TCDD during pregnancy reduced expression of the cell adhesion molecule E-cadherin in the mammary gland and decreased phosphorylation of STAT5, a known regulator of β-casein gene expression. These data provide morphological and molecular evidence that TCDD-mediated AhR activation disrupts structural and functional differentiation of the mammary gland, and present an in vitro model for studying the effects of TCDD on mammary epithelial cell function. PMID:19490989

  9. Botulism in 2 urban dogs

    PubMed Central

    Uriarte, Ane; Thibaud, Jean-Laurent; Blot, Stéphane

    2010-01-01

    Two dogs from the same owner were referred for ascending weakness and paresis of 2 to 3 days duration. Electromyography and electroneurography determined that there were normal F-waves, decreased compound action potential, and decreased activity on repetitive nerve stimulation. These findings were valuable in diagnosing botulism in the dogs. PMID:21197207

  10. Neuromuscular disease in a dog.

    PubMed

    Bors, M; Valentine, B A; de Lahunta, A

    1988-10-01

    Diffuse neuromuscular disease occurs sporadically in dogs. The most commonly reported diffuse neuromuscular diseases are polyradiculoneuritis (coonhound paralysis), tick paralysis, botulism, and myasthenia gravis (1,2,12). This clinical report describes an atypical presentation of a diffuse neuromuscular disease in a dog. PMID:3168469

  11. Nodular panniculitis in the dog.

    PubMed

    Baker, B B; Stannard, A A

    1975-10-15

    Nodular panniculitis, a granulomatous inflammatory disease of the subcutaneous fat, was diagnosed in 11 dogs. Clinically, the disease was characterized by development of subcutaneous nodules and intermittent fever and anorexia. Short-term corticosteroid therapy was effective in 10 of the 11 dogs. PMID:1237484

  12. Ureteral fibropapilloma in a dog.

    PubMed

    Hattel, A L; Diters, R W; Snavely, D A

    1986-04-15

    A fibropapilloma was found to involve the left ureter in a 7-year-old castrated male Doberman Pinscher dog. Severe unilateral hydronephrosis and hydroureter were associated with the ureteral mass. Treatment consisted of unilateral nephrectomy and ureterectomy. This case represents an additional type of primary ureteral neoplasm found in the dog. PMID:3710881

  13. Retrobulbar chondrosarcoma in a dog

    PubMed Central

    Ralić, M.; Vasić, J.; Jovanović, M.; Cameron, B.

    2014-01-01

    This paper presents a review of a dog, with a retrobulbar chondrosarcoma, which was admitted for surgery for visible changes in his eye during inspection. Orbital neoplasia in dogs may be primary and secondary. Sixty percent of orbital neoplasia in dogs are primary, ninety percent of which are malignant. Retrobulbar neoplasms are rare and in their early stage represent a diagnostic challenge. Chondrosarcoma of the skull is a slow-progressing malignant disease which occurs locally, aggressive with invasion into the surrounding tissues. Dogs with chondrosarcoma of the skull have life expectancy between 210 and 580 days - in our case it was 180 days - after the first alterations on the eye of the dog occurred. PMID:26623338

  14. MDSCs Mediate Angiogenesis and Predispose Canine Mammary Tumor Cells for Metastasis via IL-28/IL-28RA (IFN-λ) Signaling

    PubMed Central

    Mucha, Joanna; Majchrzak, Kinga; Taciak, Bartłomiej; Hellmén, Eva; Król, Magdalena

    2014-01-01

    Background Myeloid-derived suppressor cells (MDSCs) function in immunosuppression and tumor development by induction of angiogenesis in a STAT3-dependent manner. Knowledge of MDSC biology is mainly limited to mice studies, and more clinical investigations using spontaneous tumor models are required. Here we performed in vitro experiments and clinical data analysis obtained from canine patients. Methods Using microarrays we examined changes in gene expression in canine mammary cancer cells due to their co-culture with MDSCs. Further, using Real-time rt-PCR, Western blot, IHC, siRNA, angiogenesis assay and migration/invasion tests we examined a role of the most important signaling pathway. Results In dogs with mammary cancer, the number of circulating MDSCs increases with tumor clinical stage. Microarray analysis revealed that MDSCs had significantly altered molecular pathways in tumor cells in vitro. Particularly important was the detected increased activation of IL-28/IL-28RA (IFN-λ) signaling. The highest expression of IL-28 was observed in stage III/IV mammary tumor-bearing dogs. IL-28 secreted by MDSCs stimulates STAT3 in tumor cells, which results in increased expression of angiogenic factors and subsequent induction of angiogenesis by endothelial cells, epithelial-mesenchymal transition (EMT) and increased migration of tumor cells in vitro. Knockdown of IL-28RA decreased angiogenesis, tumor cell invasion and migration. Conclusions We showed for the first time that MDSCs secrete IL-28 (IFN-λ), which promotes angiogenesis, EMT, invasion and migration of tumor cells. Thus, IL-28 may constitute an interesting target for further therapies. Moreover, the similarity in circulating MDSC levels at various tumor clinical stages between canine and human patients indicates canines as a good model for clinical trials of drugs targeting MDSCs. PMID:25075523

  15. Rotary slot dog

    DOEpatents

    Cutburth, Ronald W.; Smauley, David A.

    1987-01-01

    A clamp or dog is disclosed which preferably comprises a slotted stepped cylindrical body which is inserted into a hole in a workpiece and then fastened to a base or fixture using a screw which is inserted through the slot. The stepped configuration provides an annular clamping surface which securely clamps the workpiece against the base or fixture. The slotted cylindrical configuration permits adjustment of the workpiece and retaining clamp in any direction, i.e., over 360.degree., relative to the mounting position of the screw in the base or fixture.

  16. When You Meet a Dog Guide.

    ERIC Educational Resources Information Center

    Ulrey, Pauline

    1994-01-01

    Tips are offered for use in an encounter with a dog guide and its blind owner. Tips include approaching the person from the right side, not taking hold of the dog guide's harness, not offering food to the dog guide, and not petting the dog guide without the owner's permission. (JDD)

  17. Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma

    SciTech Connect

    Abelson, Jonathan A.; Murphy, James D.; Minn, Ann Yuriko; Chung, Melody; Fisher, George A.; Ford, James M.; Kunz, Pamela; Norton, Jeffrey A.; Visser, Brendan C.; Poultsides, George A.; Koong, Albert C.; Chang, Daniel T.

    2012-03-15

    Purpose: To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma. Methods and Materials: Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively. Results: The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%). Conclusions: Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

  18. Increased efficacy of photodynamic therapy of R3230AC mammary adenocarcinoma by intratumoral injection of Photofrin II.

    PubMed Central

    Gibson, S. L.; van der Meid, K. R.; Murant, R. S.; Hilf, R.

    1990-01-01

    Photodynamic therapy consists of the systemic administration of a derivative of haematoporphyrin (Photofrin II) followed 24-72 h later by exposure of malignant lesions to photoradiation. We investigated the efficacy of this treatment after direct intratumoral injection of Photofrin II. This direct treatment regimen resulted in higher rates of inhibition of mitochondrial cytochrome c oxidase (5.13% J-1 cm-2 x 10(-1) and succinate dehydrogenase (3.14% J-1 cm-2 x 10(-1] in vitro at 2 h after intratumoral injection compared to rates of inhibition obtained after intraperitoneal drug administration: 0.51 and 0.42% J-1 cm-2 x 10(-1), respectively. A significant delay in tumour growth in vivo was observed in animals that received intratumoral injections 2 h before photoradiation compared to animals injected intraperitoneally at either 2 or 24 h before photoradiation. The treatment protocols were compared with control groups, consisting of Photofrin II administration intratumorally or intraperitoneally without photoradiation, or photoradiation in the absence of Photofrin II. These data indicate that the intratumoral injection regimen with Photofrin II enhanced the efficacy of photodynamic therapy. The greater delay in tumour growth observed after intratumoral administration of Photofrin II suggests a mechanism favouring direct cell damage. PMID:2139578

  19. Diagnostic and prognostic impact of cytochemically assessed nuclear DNA contents in human adenocarcinomas of the mammary gland.

    PubMed

    Askensten, U

    1988-01-01

    Cytochemical assessments of the nuclear DNA contents in carcinomas of the breast can be used for both prognostic and diagnostic purposes. Two main techniques are currently being used, viz. flow cytometry (FCM) and microspectrophotometry (MSP). An account of their advantages and disadvantages is given. In addition, an old, rather crude, cytophotometric technique can be used for histopathological sections of paraffin-embedded specimens. The principal sampling procedures are fine-needle aspiration biopsy and the so-called imprint technique, where the specimens are made from the cut surface of the freshly excised operation specimen. Paraffin-embedded histopathological material can also be used, applying a newly developed MSP procedure, where isolated nuclei from deparaffinized/disintegrated specimens are analyzed. Most important is that intact cell nuclei, representative for the whole tumour nodule, can be obtained. The simultaneous use of FCM and MSP is also of utmost importance for the reliability in the interpretation of the results. Then, a kind of "DNA malignancy grading" is obtained that in several investigations has proven itself to be an excellent prognosticating tool that can be used for making an adequate choice of therapy for the individual patient. The diagnostic value of the results of the cytochemically assessed nuclear DNA distribution patterns is not so high as the prognostic one. Tumours with a diploid type of nuclear DNA content can be found both among benign and malignant neoplasms. However, a neoplasm with an aneuploid DNA distribution pattern can almost certainly be considered highly malignant. PMID:3066302

  20. Biosynthesis of ascites sialoglycoprotein-1, the major O-linked glycoprotein of 13762 rat mammary adenocarcinoma ascites cells

    SciTech Connect

    Spielman, J.

    1987-01-01

    The present studies were undertaken to determine the timing of the major events in biosynthesis, and to characterize the contributions of chain initiation and elongation in maturation of the glycoprotein. Initiation of the earliest O-linked chains was detected by analysis of conversion of {sup 3}H-thr to {sup 3}H 2-aminobutyrate following mild alkaline borohydride elimination of O-linked sugars from peanut lectin-precipitated ASGP-1. Initiation was detected within 5 min of translation; amino sugar analysis of GlcNH{sub 2}-labeled, trypsinized cells also showed that GalNAc was added as late as 5 min prior to arrival of ASGP-1 at the cell surface. Thus initiation occurs throughout biosynthesis. Maturation of the glycoprotein from a lightly-glycosylated immature form to the heavily-glycosylated mature from involved both continued initiation of new chains and chain elongation, and occurred with a half-time of about 30 min. Analysis of labeled ASGP-1 released from the cell surface by trypsinization showed that although some newly-synthesized ASGP-1 reached the cell surface within 70-80 min of protein synthesis, the half-time for appearance of mature glycoprotein was in excess of 4 hr, indicating that most molecules reside in an intracellular compartment(s) for a considerable time.

  1. Parathyroid adenocarcinoma in a nephropathic Persian cat.

    PubMed

    Cavana, Paola; Vittone, Valentina; Capucchio, Maria T; Farca, Anna M

    2006-10-01

    This report describes an uncommon clinical case of cystic parathyroid adenocarcinoma. A 17-year-old male Persian cat was presented for evaluation of a ventral cervical mass. The cat was inappetent and showed weight loss, polydipsia and vomiting. Serum biochemistry and urinalysis revealed moderate hypercalcaemia, a mild increase of creatinine, isosthenuria and proteinuria. Sodium dodecyl sulphate-agarose gel electrophoresis showed a mixed tubular proteinuric pattern, in accordance with histological examination that revealed interstitial nephritis and glomerulonephritis. Diagnosis of parathyroid carcinoma was based on histopathological findings. PMID:16651017

  2. Bony metaplasia in a caecum adenocarcinoma.

    PubMed

    Mogoantă, S S; Meşină, C; Streba, Liliana; Predescu, Anca; Mateescu, Garofiţa Olivia; Muţiu, Gabriela; Mogoantă, L

    2012-01-01

    Ectopic bone formation in the digestive tract is a very rare phenomenon in pathology. Most cases of bone metaplasia were found in distal colon tumors, rectum and sigmoid respectively. We present a case of well-differentiated adenocarcinoma of the caecum (the second case of literature) associated with bone metaplasia, which debuted atypical, with symptoms of infectious enterocolitis, in a 72-year-old female patient, with no history of digestive pathology. Highlighting bone metaplasia was achieved by current histological techniques. Patient's evolution was favorable with surgical treatment and chemotherapy. PMID:23188448

  3. Cytogenetic findings in a large bowel adenocarcinoma.

    PubMed

    Ferti-Passantonopoulou, A; Panani, A; Avgerinos, A; Raptis, S

    1986-04-15

    Cytogenetic analysis of a biopsy specimen taken during sigmoidoscopy from an adenocarcinoma of the large bowel revealed a hypodiploid karyotype with numerical and structural abnormalities identified as trisomy 7, t(3;12), t(1;17), interstitial deletion of the long arm of a chromosome #5 and loss of the Y chromosome with double X chromosomes. The possibility of this karyotype being a further evolutionary step in a subgroup of large bowel cancers and the clinical value of the above findings are discussed. PMID:3456826

  4. Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

    ERIC Educational Resources Information Center

    Jaffe, J. S.; Chambers, J. T.

    2005-01-01

    Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. Conclusion:…

  5. P53 expression in invasive pancreatic adenocarcinoma and precursor lesions.

    PubMed

    Norfadzilah, M Y; Pailoor, Jayalakshmi; Retneswari, M; Chinna, K; Noor, Laili M M

    2011-12-01

    Patients with pancreatic adenocarcinoma are known to have a high mortality rate. The 5-year survival rate still remains low even now compared to that of the 1960's despite new advances in management including surgery, chemotherapy, pathological classification and molecular diagnostic technologies. Precursors to invasive pancreatic adenocarcinoma have been identified in the last ten years that include mucinous cystic neoplasm, intraductal papillary mucinous neoplasm and pancreatic intraepithelial neoplasia. p53 protein accumulation in the nuclei is a common molecular event in most human neoplasms. Our objective is to investigate p53 expression in pancreatic adenocarcinoma and precursor lesions and their significance. The selected study material encompassed 31 invasive ductal adenocarcinoma, 15 mucinous cystic neoplasm and papillary mucinous neoplasm, and 27 cases of pancreatic intraepithelial neoplasia including grade 1, 2 and 3. Immunoscore was given for each case based on intensity of staining and percentage of cells positive and compared between precursor lesions and invasive adenocarcinoma. A score of 50 and above was considered significant. The results showed that p53 expression increased progressively and significantly with the grade of pancreatic intraepithelial neoplasia and adenocarcinoma (p-value < 0.001). These findings support the concept of multistep carcinogenesis in pancreatic adenocarcinoma and suggest that p53 inactivation occurs in the progression of precursors to pancreatic adenocarcinoma. PMID:22299208

  6. Dimethylarginine dimethylaminohydrolase 2 promotes tumor angiogenesis in lung adenocarcinoma.

    PubMed

    Shiozawa, Toshihiro; Iyama, Shinji; Toshima, Shotaro; Sakata, Akiko; Usui, Shingo; Minami, Yuko; Sato, Yukio; Hizawa, Nobuyuki; Noguchi, Masayuki

    2016-02-01

    Although embryonal proteins have been used as tumor marker, most are not useful for detection of early malignancy. In the present study, we developed mouse monoclonal antibodies against fetal lung of miniature swine, and screened them to find an embryonal protein that is produced at the early stage of malignancy, focusing on lung adenocarcinoma. We found an antibody clone that specifically stained stroma of lung adenocarcinoma. LC-MS/MS identified the protein recognized by this clone as dimethylarginine dimethylaminohydrolase 2 (DDAH2), an enzyme known for antiatherosclerotic activity. DDAH2 was found to be expressed in fibroblasts of stroma of malignancies, with higher expression in minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma than in adenocarcinoma in situ (AIS). Moreover, tumors with high stromal expression of DDAH2 had a poorer prognosis than those without. In vitro analysis showed that DDAH2 increases expression of endothelial nitric oxide synthase (eNOS), inducing proliferation and capillary-like tube formation of vascular endothelial cells. In resected human tissues, eNOS also showed higher expression in invasive adenocarcinoma than in AIS and normal lung, similarly to DDAH2. Our data indicate that expression of DDAH2 is associated with invasiveness of lung adenocarcinoma via tumor angiogenesis. DDAH2 expression might be a prognostic factor in lung adenocarcinoma. PMID:26515557

  7. Cervical adenocarcinoma identification by testing for chromosomal abnormalities.

    PubMed

    Dittus, Janet L; Dudley, Bunyan S; Upender, Madhvi; Endress, Gregory A

    2013-12-01

    We report on a case of cervical adenocarcinoma in situ in a 42-year-old woman with a history of human papillomavirus infection. Repeat cytology, human papillomavirus testing, and colposcopy failed to identify the lesion. Testing of the cervical cell DNA identified chromosomal abnormalities, prompting a cervical cone biopsy, which identified adenocarcinoma in situ. PMID:24283864

  8. Neuropilin-2 promotes branching morphogenesis in the mouse mammary gland.

    PubMed

    Goel, Hira Lal; Bae, Donggoo; Pursell, Bryan; Gouvin, Lindsey M; Lu, Shaolei; Mercurio, Arthur M

    2011-07-01

    Although the neuropilins were characterized as semaphorin receptors that regulate axon guidance, they also function as vascular endothelial growth factor (VEGF) receptors and contribute to the development of other tissues. Here, we assessed the role of NRP2 in mouse mammary gland development based on our observation that NRP2 is expressed preferentially in the terminal end buds of developing glands. A floxed NRP2 mouse was bred with an MMTV-Cre strain to generate a mammary gland-specific knockout of NRP2. MMTV-Cre;NRP2(loxP/loxP) mice exhibited significant defects in branching morphogenesis and ductal outgrowth compared with either littermate MMTV-Cre;NRP2(+/loxP) or MMTV-Cre mice. Mechanistic insight into this morphological defect was obtained from a mouse mammary cell line in which we observed that VEGF(165), an NRP2 ligand, induces branching morphogenesis in 3D cultures and that branching is dependent upon NRP2 as shown using shRNAs and a function-blocking antibody. Epithelial cells in the mouse mammary gland express VEGF, supporting the hypothesis that this NRP2 ligand contributes to mammary gland morphogenesis. Importantly, we demonstrate that VEGF and NRP2 activate focal adhesion kinase (FAK) and promote FAK-dependent branching morphogenesis in vitro. The significance of this mechanism is substantiated by our finding that FAK activation is diminished significantly in developing MMTV-Cre;NRP2(loxP/loxP) mammary glands compared with control glands. Together, our data reveal a VEGF/NRP2/FAK signaling axis that is important for branching morphogenesis and mammary gland development. In a broader context, our data support an emerging hypothesis that directional outgrowth and branching morphogenesis in a variety of tissues are influenced by signals that were identified initially for their role in axon guidance. PMID:21693513

  9. Progesterone receptor isoform analysis by quantitative real-time polymerase chain reaction in formalin-fixed, paraffin-embedded canine mammary dysplasias and tumors.

    PubMed

    Guil-Luna, S; Stenvang, J; Brünner, N; Sánchez-Céspedes, R; Millán, Y; Gómez-Laguna, J; de las Mulas, J Martín

    2014-09-01

    Cloning and sequencing of the progesterone receptor gene in dogs have revealed 2 isoforms, A and B, transcribed from a single gene. Distribution of isoforms A and B in canine mammary lesions has hitherto been investigated only by Western blot analysis. This study analyzed progesterone receptor and its isoforms in formalin-fixed, paraffin-embedded tissue samples from canine mammary lesions (4 dysplasias, 10 benign tumors, and 46 carcinomas) using 1-step SYBR Green quantitative real-time polymerase chain reaction (RT-qPCR). Progesterone receptor was expressed in 75% of dysplasias, all benign tumors, and 59% of carcinomas. Carcinomas, and particularly simple epithelial-type carcinomas, displayed the lowest levels of expression. A high rate of agreement was recorded between RT-qPCR and immunohistochemical labeling. Isoforms A and B were successfully amplified, with correlation coefficients of 0.99 and amplification efficiencies close to 2, and were expressed in all lesion types analyzed. Predominance of A over B expression was observed in carcinomas and complex adenomas. Low-grade tumors exhibited higher progesterone receptor messenger RNA (mRNA) levels, but no difference was observed in the expression of isoform A versus B. Analysis of progesterone receptor mRNA isoforms by RT-qPCR was successful in routinely formalin-fixed, paraffin-embedded tissue samples and enabled the distribution of isoforms A and B to be identified for the first time in dysplasias, benign tumors, and malignant tumors of the canine mammary gland. These findings will facilitate future research into the role of progesterone receptor isoforms in the progression of canine mammary tumors. PMID:24249219

  10. INDUCTION OF MAMMARY GLAND DEVELOPMENT IN ESTROGEN RECEPTOR-ALPHA KNOCKOUT MICE

    EPA Science Inventory

    Mammary glands from the estrogen receptor knockout ( ERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted Er signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute t...

  11. Use of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Adrenal Tumors in Dogs.

    PubMed

    Bargellini, Paolo; Orlandi, Riccardo; Dentini, Alfredo; Paloni, Chiara; Rubini, Giuseppe; Fonti, Paolo; Diana, Alessia; Peterson, Mark E; Boiti, Cristiano

    2016-01-01

    We evaluated the diagnostic accuracy of the contrast-enhanced ultrasonography (CEUS), using a second-generation microbubble contrast agent, in differentiating the different types of adrenal mass lesions in 24 dogs. At B-mode ultrasound, 9 lesions involved the right adrenal gland, 14 the left, and 1 was bilateral. Each dog received a bolus of the contrast agent into the cephalic vein, immediately followed by a 5-mL saline flush. The first contrast enhancement of each adrenal lesion was evaluated qualitatively to assess the degree of enhancement and its distribution during the wash-in and wash-out phases, as well as the presence of non-vascularized areas and specific vascular patterns. Pathological diagnoses were determined in all dogs by histopathology or by cytology. Combining enhancement degree and vascularity resulted in the best predictive model, allowing CEUS to differentiate adrenocortical adenoma (n=10), adenocarcinoma (n=7), and pheochromocytoma (n=7) with an accuracy of 91.7% (P < 0.001). Combining enhancement degree and vascularity, CEUS can discriminate malignant versus benign adrenal lesions with a sensitivity of 100.0%, a specificity of 80.0%, and an accuracy of 91.7% (P < 0.001). In conclusion, results of this study confirm that CEUS is useful for differentiating between the different types of adrenal tumors in dogs. PMID:27008325

  12. Chemoradiation in pancreatic adenocarcinoma: a literature review.

    PubMed

    Roy, Rajarshi; Maraveyas, Anthony

    2010-01-01

    Adenocarcinoma of the exocrine pancreas has an annual incidence of 7,400 cases in the U.K. In comparison with other common cancers of solid organs, namely, breast, colorectal, and prostate cancer, pancreatic cancer has a high morbidity and mortality. Radical resection is possible in only 15%-20% of patients, and only 3%-4% of all patients presenting with this condition achieve long-term control and cure. Various strategies in the form of neoadjuvant and adjuvant treatment have been employed over the years to improve outcome, with limited success. Systemic chemotherapy remains the gold standard in the metastatic setting in good performance status patients, and adjuvant chemotherapy after resection of localized and locally advanced cancer has been found to improve outcome. The role of radiotherapy, however, remains controversial and is an area that merits further investigation in well-conducted multicenter trials at various stages of the disease in combination with systemic agents and exploiting recent advances in the delivery of radiotherapy. In this article, we review the published literature on the use of chemoradiation as a modality in various stages of pancreatic adenocarcinoma and highlight areas that future trials in this field should target for a way forward in this malignancy. PMID:20203172

  13. Neoadjuvant treatment for resectable pancreatic adenocarcinoma.

    PubMed

    Wong, John; Solomon, Naveenraj L; Hsueh, Chung-Tsen

    2016-02-10

    Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress. PMID:26862486

  14. Aggressive papillary adenocarcinoma on atypical localization

    PubMed Central

    Balci, Mecdi Gurhan; Tayfur, Mahir; Deger, Ayse Nur; Cimen, Orhan; Eken, Huseyin

    2016-01-01

    Abstract Introduction: Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland tumor that is found on the fingers, toes, and the digits. To date, <100 cases have been reported in the literature. Apart from 1 case reported in the thigh, all of them were on digital or nondigital acral skin. Case presentation: A 67-year-old Caucasian woman was admitted to the hospital due to a mass on the scalp. This lesion was present for almost a year. It was a semimobile cyctic mass that elevated the scalp. There was no change in the skin color. Its dimensions were 1.5 × 1 × 0.6 cm. The laboratory, clinic, and radiologic findings (head x-ray) of the patient were normal. It was evaluated as a benign lesion such as lipoma or epidermal cyst by a surgeon due to a small semimobile mass and no erosion of the skull. It was excised by a local surgery excision. The result of the pathologic examination was aggressive papillary adenocarcinoma. This diagnosis is synonymous with ADPA. Conclusion: In our case, localization was scalp. This localization is the first for this tumor in the literature. In addition, another atypical localization of this tumor (ADPA) is thigh in the literature. This case was presented due to both the rare and atypical localizations. That is why, in our opinion, revision of “digital” term in ADPA is necessary due to seem in atypical localizations like thigh and scalp. PMID:27428196

  15. Neoadjuvant treatment for resectable pancreatic adenocarcinoma

    PubMed Central

    Wong, John; Solomon, Naveenraj L; Hsueh, Chung-Tsen

    2016-01-01

    Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress. PMID:26862486

  16. Modeling mechanical interactions between cancerous mammary acini

    NASA Astrophysics Data System (ADS)

    Wang, Jeffrey; Liphardt, Jan; Rycroft, Chris

    2015-03-01

    The rules and mechanical forces governing cell motility and interactions with the extracellular matrix of a tissue are often critical for understanding the mechanisms by which breast cancer is able to spread through the breast tissue and eventually metastasize. Ex vivo experimentation has demonstrated the the formation of long collagen fibers through collagen gels between the cancerous mammary acini responsible for milk production, providing a fiber scaffolding along which cancer cells can disorganize. We present a minimal mechanical model that serves as a potential explanation for the formation of these collagen fibers and the resultant motion. Our working hypothesis is that cancerous cells induce this fiber formation by pulling on the gel and taking advantage of the specific mechanical properties of collagen. To model this system, we employ a new Eulerian, fixed grid simulation method to model the collagen as a nonlinear viscoelastic material subject to various forces coupled with a multi-agent model to describe individual cancer cells. We find that these phenomena can be explained two simple ideas: cells pull collagen radially inwards and move towards the tension gradient of the collagen gel, while being exposed to standard adhesive and collision forces.

  17. Expression of cyclooxygenase-2 in neoplasms of the mammary gland in bitches.

    PubMed

    Badowska-Kozakiewicz, A M; Malicka, E

    2010-01-01

    The aim of the study was to investigate the cyclooxygenase-2 expression in correlation with other neoplasm traits such as: histological type, the differentiation grade, proliferative activity, estrogenic receptor, as well as Hsp70 and p53 proteins expression. Material for the investigation comprised mammary gland tumours, collected from dogs, the patients of veterinary clinics, during surgical procedures. All together 14 adenomas, 66 complex carcinomas, 47 simple carcinomas and 6 solid carcinomas were studied. Evaluations were conducted with histopathological and immunohistochemical methods using suitable antibodies. Expression of COX-2 was observed in 95% of cancers, in case of which, the complex cancers constituted the highest percentage (48.4%). The highest expression of COX-2 was revealed in simple and complex cancers and in cancers with the 3rd degree of histological malignancy. The significant correlation between expression of COX-2 and high mean value of the mitotic index was found. The high expression of COX-2 was also correlated with the expression of protein p53 and expression of the protein Hsp 70. Obtained results suggest that cyclooxygenase-2 may be a prognostic factor, but it requires detailed clinical confirmation. PMID:20731190

  18. Immunohistochemical expression of protein p53 in neoplasms of the mammary gland in bitches.

    PubMed

    Rodo, A; Malicka, E

    2008-01-01

    The aim of the study was to investigate the presence of protein p53 in correlation with other tumor traits: histological type, tumor grade and proliferative activity. Material for the investigation comprised mammary gland tumours collected from dogs, the patients of veterinary clinics, during surgical procedures, and archival samples. Alltogether 21 adenomas, 31 complex carcinomas, 35 simple carcinomas and 12 solid carcinomas were qualified for further investigation. No protein p53 expression was found in adenomas. Cancers show positive reaction in 32.5%. The highest percent of p53 positive neoplasms was observed in solid carcinomas and neoplasms with the highest degree of histological malignancy. The smallest number showing this expression was observed in adenomas and the highest was characteristic for solid carcinomas. Considering the tumour grading, it was found that an increase in neoplasm malignancy was positively correlated with the number of the cells showing the expression of protein p53. The differences were statistically significant. Statistically significant positive correlations were observed between the proliferative activity and protein p53 expression. Higher accumulation of protein p53 in more malignant neoplasms suggests that mutations of protein p53 can be responsible for higher proliferation in neoplasms with advanced progression of malignancy. PMID:18683536

  19. Oncolytic reovirus synergizes with chemotherapeutic agents to promote cell death in canine mammary gland tumor.

    PubMed

    Igase, Masaya; Hwang, Chung Chew; Kambayashi, Satoshi; Kubo, Masato; Coffey, Matt; Miyama, Takako Shimokawa; Baba, Kenji; Okuda, Masaru; Noguchi, Shunsuke; Mizuno, Takuya

    2016-01-01

    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. PMID:26733729

  20. Isolation of Endoplasmic Reticulum Fractions from Mammary Epithelial Tissue.

    PubMed

    Chanat, Eric; Le Parc, Annabelle; Lahouassa, Hichem; Badaoui, Bouabid

    2016-06-01

    In the mammary glands of lactating animals, the mammary epithelial cells that surround the lumen of the acini produce and secrete copious amounts of milk. Functional differentiation of these mammary epithelial cells depends on the development of high-efficiency secretory pathways, notably for protein and lipid secretion. Protein secretion is a fundamental process common to all animal cells that involves a subset of cellular organelles, including the endoplasmic reticulum and the Golgi apparatus. In contrast, en masse secretion of triglycerides and cholesterol esters in the form of milk fat globules is a unique feature of the mammary epithelial cell. Cytoplasmic lipid droplets, the intracellular precursors of milk fat globules, originate from the endoplasmic reticulum, as do most milk-specific proteins. This organelle is therefore pivotal in the biogenesis of milk components. Fractionation of the cell into its subcellular parts is an approach that has proven very powerful for understanding organelle function and for studying the specific role of an organelle in a given cell activity. Here we describe a method for the purification of both smooth and rough microsomes, the membrane-bound endoplasmic reticulum fragments that form from endoplasmic reticulum domains when cells are broken up, from mammary gland tissue at lactation. PMID:27048289

  1. Classification and grading of canine malignant mammary tumors

    PubMed Central

    Tavasoly, Abbas; Golshahi, Hannaneh; Rezaie, Annahita; Farhadi, Mohammad

    2013-01-01

    Histological grading is a good parameter to stratify tumors according to their biological aggressiveness. The Elston and Ellis grading method in humans, invasive ductal breast carcinomas and other invasive tumors are routinely used. The aims of this study were classification of mammary gland tumors and also application of a human grading method in canine mammary carcinoma. The samples included 37 tumors of mammary glands. Mammary tumors were carcinomas (n = 32) and sarcomas (n = 5). The carcinomas were classified as simple carcinoma 56.8% (n = 21), complex carcinoma 13.5% (n = 5), carcinoma arising from benign tumor 10.8% (n= 4) and special type of carcinoma 5.4% (n = 2). Out of 32 carcinomas studied, 37.5% (n = 12) grade I, 46.9% (n = 15) grade II and 15.6% (n = 5) grade III. This study demonstrated that the Elston and Ellis method of histological grading in canine mammary tumor is a reliable prognostic factor which is correlated with histopathological classification. PMID:25593682

  2. Pulmonary-type adenocarcinoma and signet ring mucinous adenocarcinoma arising in an ovarian dermoid cyst: report of a unique case.

    PubMed

    Boyd, Clinton; Patel, Kaushik; O'Sullivan, Brendan; Taniere, Philippe; McCluggage, W Glenn

    2012-11-01

    Dermoid cysts are common benign ovarian germ cell neoplasms. Occasionally, one of the mature elements undergoes malignant transformation resulting in the formation of a somatic malignancy; most commonly this is squamous carcinoma. We report a unique case where 2 separate malignancies arose within a dermoid cyst, one a signet ring mucinous adenocarcinoma and the other a pulmonary-type adenocarcinoma. There have been only occasional earlier case reports of a possible pulmonary-type adenocarcinoma arising in a dermoid cyst. In the case we report, the pulmonary-type adenocarcinoma was closely associated with a bronchial structure and exhibited diffuse positive immunohistochemical staining with TTF1, PE10, and napsin A. Molecular studies revealed no evidence of epidermal growth factor receptor mutation, a molecular alteration which may be found in primary pulmonary adenocarcinoma. PMID:23026196

  3. Misregulation of Stromelysin-1 in Mouse Mammary Tumor Cells Accompanies Acquisition of Stromelysin-1 dependent Invasive Properties

    SciTech Connect

    Lochter, A.; Srebrow, A.; Sympson, C.J.; Terracio, N.; Werb, Z.; Bissell, M.J.

    1997-02-21

    Stromelysin-1 is a member of the metalloproteinase family of extracellular matrix-degrading enzymes that regulates tissue remodeling. We previously established a transgenic mouse model in which rat stromelysin-1 targeted to the mammary gland augmented expression of endogenous stromelysin-1, disrupted functional differentiation, and induced mammary tumors. A cell line generated from an adenocarcinoma in one of these animals and a previously described mammary tumor cell line generated in culture readily invaded both a reconstituted basement membrane and type I collagen gels, whereas a nonmalignant, functionally normal epithelial cell line did not. Invasion of Matrigel by tumor cells was largely abolished by metalloproteinase inhibitors, but not by inhibitors of other proteinase families. Inhibition experiments with antisense oligodeoxynucleotides revealed that Matrigel invasion of both cell lines was critically dependent on stromelysin-1 expression. Invasion of collagen, on the other hand, was reduced by only 40-50%. Stromelysin-1 was expressed in both malignant and nonmalignant cells grown on plastic substrata. Its expression was completely inhibited in nonmalignant cells, but up-regulated in tumor cells, in response to Matrigel. Thus misregulation of stromelysin-1 expression appears to be an important aspect of mammary tumor cell progression to an invasive phenotype. The matrix metalloproteinases (MMPs) are a family of extracellular matrix (ECM)-degrading enzymes that have been implicated in a variety of normal developmental and pathological processes, including tumorigenesis. The MMP family comprises at least 15 members with different, albeit overlapping, substrate specificities. During activation of latent MMPs, their propeptides are cleaved and they are converted to a lower molecular weight form by other enzymes, including serine proteinases, and by autocatalytic cleavage. Among the MMPs, stromelysin-1 (SL1) possesses the broadest substrate specificity. Despite

  4. In vitro expansion of the mammary stem/progenitor cell population by xanthosinetreatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Mammary stem cells are critical for growth and maintenance of the mammary gland and therefore of considerable interest for improving productivity and efficiency of dairy animals. Xanthosine (Xs) treatment has been demonstrated to promote expansion of putative mammary stem cells in vivo ...

  5. p62: a hub of multiple signaling pathways in HER2-induced mammary tumorigenesis

    PubMed Central

    Cai-McRae, Xiaofeng; Karantza, Vassiliki

    2015-01-01

    We recently reported that depletion of p62 in the background of human epidermal growth factor receptor 2 (HER2) overexpression sensitizes mammary tumor cells to amino acid deprivation, abolishes cellular transformation in vitro, and suppresses mammary tumorigenesis in vivo. Extensive investigation on the underlying molecular mechanisms has revealed a multifaceted role for p62 in HER2-associated mammary tumorigenesis. PMID:27308451

  6. Expression of novel, putative stem cell markers in prepubertal and lactating mammary glands of bovine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary stem cells (MaSC) are essential for growth and maintenance of the mammary epithelium. Two main phases of mammary growth include ductal elongation prior to puberty and lobulo-alveolar growth and development during pregnancy. Some studies have utilized morphological characteristics and retenti...

  7. Bovine mammary stem cells: Transcriptome profiling and the stem cell niche

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Identification and transcriptome analysis of mammary stem cells (MaSC) are important steps toward understanding the molecular basis of mammary epithelial growth, homeostasis and tissue repair. Our objective was to evaluate the molecular profiles of four categories of cells within the bovine mammary ...

  8. Enrichment of Mammary Basal and Luminal Cells for Cell-of-Origin Metastasis Studies.

    PubMed

    Kabeer, Farhia; Podsypanina, Katrina; Darrasse-Jèze, Guillaume

    2016-01-01

    The mammary gland is an important model system in metastasis research. Mammary epithelial stem cells are of particular interest because of their capacity for regeneration and their role in cancer initiation. This protocol describes how to enrich for mammary basal and luminal epithelial cells using fluorescence-activated cell sorting (FACS). PMID:26832681

  9. Cutaneous mastocytosis with a mutation in the juxtamembrane domain of c-kit in a young laboratory beagle dog

    PubMed Central

    Kato, Yuki; Kashiwagi, Emi; Masuno, Koichi; Fujisawa, Kae; Tsuchiya, Noriko; Matsushima, Shuuichi; Torii, Mikinori; Takasu, Nobuo

    2015-01-01

    Cutaneous mastocytosis, which resembles a subset of urticaria pigmentosa in humans, is rare in dogs. We herein report unrepresentative neoplastic proliferation of mast cells in ventral skin removed routinely from a nine-month-old female laboratory beagle dog at necropsy. A histological examination revealed diffuse extensive cellular infiltration from the superficial to deep dermis in most parts of the skin around the fourth and fifth mammary papilla without nodule formation. Tumor cells were fairly monomorphic, well-differentiated mast cells with round nuclei of small distinct nucleoli and moderate to abundant, slightly eosinophilic and granular cytoplasm. A perivascular arrangement of mast cells was noted at the margin of the lesions. Infiltration of eosinophils and degeneration of collagen were not observed in the dermis. Cutaneous mastocytosis was diagnosed based on these features. A sequence analysis of lesions revealed the deletion of Gln555 to Ile570 within the juxtamembrane domain of c-kit (exon 11). PMID:26989302

  10. Cutaneous mastocytosis with a mutation in the juxtamembrane domain of c-kit in a young laboratory beagle dog.

    PubMed

    Kato, Yuki; Kashiwagi, Emi; Masuno, Koichi; Fujisawa, Kae; Tsuchiya, Noriko; Matsushima, Shuuichi; Torii, Mikinori; Takasu, Nobuo

    2016-01-01

    Cutaneous mastocytosis, which resembles a subset of urticaria pigmentosa in humans, is rare in dogs. We herein report unrepresentative neoplastic proliferation of mast cells in ventral skin removed routinely from a nine-month-old female laboratory beagle dog at necropsy. A histological examination revealed diffuse extensive cellular infiltration from the superficial to deep dermis in most parts of the skin around the fourth and fifth mammary papilla without nodule formation. Tumor cells were fairly monomorphic, well-differentiated mast cells with round nuclei of small distinct nucleoli and moderate to abundant, slightly eosinophilic and granular cytoplasm. A perivascular arrangement of mast cells was noted at the margin of the lesions. Infiltration of eosinophils and degeneration of collagen were not observed in the dermis. Cutaneous mastocytosis was diagnosed based on these features. A sequence analysis of lesions revealed the deletion of Gln555 to Ile570 within the juxtamembrane domain of c-kit (exon 11). PMID:26989302

  11. Infertility in the male dog.

    PubMed

    Wallace, M S

    1992-09-01

    The diagnosis and characterization of infertility in the male dog depends largely on the initial history and semen evaluation and on following the course of infertility over time. The diagnostic testing described here is helpful for guiding therapy, but the prognosis in serious cases of infertility is usually poor. Cases of subfertility that are not progressive have a better prognosis with optimal breeding management. Finally, the clinician should remember that some insults to the testes are reversible with time so it is important not to administer therapy that will interfere with the dog's ability to recover. Client education is an important part of the management of male dog infertility because it is not uncommon for various drugs to be administered by the breeder, or at the breeder's request, without a sufficient diagnostic work-up. In addition, errors of breeding management may play a role in male dog infertility or limit the success of treatment. PMID:1421819

  12. Pseudoketogenesis in hepatectomized dogs.

    PubMed

    Des Rosiers, C; Montgomery, J A; Garneau, M; David, F; Mamer, O A; Daloze, P; Toffolo, G; Cobelli, C; Landau, B R; Brunengraber, H

    1990-03-01

    Overestimation of ketone body turnover in vivo, measured by tracer kinetics, could occur if specific activity or molar percent enrichment is diluted in extrahepatic tissues by label exchange via reversal of 3-oxoacid-CoA transferase, a process we call pseudoketogenesis. To test this hypothesis, euglycemic hepatectomized dogs were injected with a bolus of acetoacetate (0.8 mmol/kg), 32% enriched in [3,4-13C2]acetoacetate. Concentrations and labeling patterns of blood acetoacetate and R-3-hydroxybutyrate were measured by selected ion-monitoring gas chromatography-mass spectrometry. During the 60 min after bolus injection of [3,4-13C2]acetoacetate, the molar percent enrichment of blood [3,4-13C2]acetoacetate decreased to 73 +/- 3% (n = 5) in controls and to 11.5 +/- 0.8% (n = 3) during infusion of dichloroacetate, an activator of pyruvate dehydrogenase. The enrichment of R-3-hydroxy-[3,4-13C2]butyrate followed closely that of [3,4-13C2]acetoacetate. These dilutions occurred despite a net uptake of ketone bodies. Concomitantly, 10.6 +/- 2.2 (n = 5) and 6.0 +/- 2.9% (n = 3) of [13C]acetoacetate molecules were labeled on all four carbons in control and dichloroacetate-treated dogs, respectively. This uniformly labeled acetoacetate arises from partial equilibration between [3,4-13C2]acetoacetate and [1,2-13C2]acetyl-CoA via the reactions catalyzed by 3-oxoacid-CoA transferase and acetoacetyl-CoA thiolase. Our data demonstrate the reversibility of the 3-oxoacid-CoA transferase in intact extrahepatic tissues and support the concept of pseudoketogenesis. This phenomenon has been quantitated by kinetic analysis of the data. PMID:2316645

  13. Cranial mediastinal carcinomas in nine dogs.

    PubMed

    Liptak, J M; Kamstock, D A; Dernell, W S; Ehrhart, E J; Rizzo, S A; Withrow, S J

    2008-03-01

    Nine dogs were diagnosed with cranial mediastinal carcinomas. Based on histological and immunohistochemical analysis, four dogs were diagnosed with ectopic follicular cell thyroid carcinomas, one dog with ectopic medullary cell thyroid carcinoma, two dogs with neuroendocrine carcinomas and two dogs with anaplastic carcinomas. Clinical signs and physical examination findings were associated with a space-occupying mass, although one dog was diagnosed with functional hyperthyroidism. Surgical resection was attempted in eight dogs. The cranial mediastinal mass was invasive either into the heart or into the cranial vena cava in three dogs. Resection was complete in six dogs and unresectable in two dogs. All dogs survived surgery, but four dogs developed pulmonary thromboembolism and two dogs died of respiratory complications postoperatively. Adjunctive therapies included pre-operative radiation therapy (n=1) and postoperative chemotherapy (n=3). Three dogs had metastasis at the time of diagnosis, but none developed metastasis following surgery. The overall median survival time was 243 days. Local invasion, pleural effusion and metastasis did not have a negative impact on survival time in this small case series. PMID:19178660

  14. Mammary blood flow regulation in the nursing rabbit

    SciTech Connect

    Katz, M.; Creasy, R.K.

    1984-11-01

    Cardiac output and mammary blood flow distribution prior to and after suckling were studied in 10 nursing rabbits by means of radionuclide-labeled microspheres. Suckling was followed by a 5.8% rise in cardiac output and a 20.4% rise in mammary blood flow. Determinations of intraglandular blood flow distribution have shown that there was a 43% increase in blood flow to the glands suckled from as compared to a 22.7% rise to the contralateral untouched glands and a 4.9% rise in the remainder of untouched glands. The conclusion is that a local mechanism may be involved in the regulation of mammary blood flow in the nursing rabbit.

  15. Survivin and related proteins in canine mammary tumors: immunohistochemical expression.

    PubMed

    Bongiovanni, L; Romanucci, M; Malatesta, D; D'Andrea, A; Ciccarelli, A; Della Salda, L

    2015-03-01

    Survivin is reexpressed in most human breast cancers, where its expression has been associated with tumor aggressiveness, poor prognosis, and poor response to therapy. Survivin expression was evaluated in 41 malignant canine mammary tumors (CMTs) by immunohistochemistry, in relation to histological grade and stage, and correlated with that of some related molecules (β-catenin, caspase 3, heat shock proteins) to understand their possible role in canine mammary tumorigenesis. An increase in nuclear survivin expression, compared with healthy mammary glands, was observed in CMTs, where nuclear immunolabeling was related to the presence of necrosis. No statistically significant relation was found between the expression of the investigated molecules and the histological grade or stage. The present study may suggest an important involvement of survivin in CMT tumorigenesis. Its overexpression in most of the cases evaluated might suggest that targeting survivin in CMTs may be a valid anticancer therapy. PMID:24686389

  16. Oxytocin binding by myoepithelial cell membranes from involuted mammary tissue.

    PubMed

    Ruberti, A; Olins, G M; Eakle, K A; Bremel, R D

    1983-04-29

    Oxytocin binding activity of myoepithelial cell membranes from mammary tissue was measured under a variety of different experimental conditions. Mammary tissue from non-lactating rats bound oxytocin with a Kd of 9.2 +/- 1.6 nM (+/- S.E.) and indicates that receptors are retained by the myoepithelial cells in a non-lactating state. Ovariectomy of non-lactating rats did not depress the binding activity of the membranes. Administration of the estrogenic compounds estradiol-17 beta and diethylstibestrol at doses which affect uterine weight and are known to increase uterine oxytocin binding did not influence the binding activity of the myoepithelial cells. This indicates that the oxytocin receptors of the mammary gland are not under the same endocrine control as the uterine receptors. PMID:6303330

  17. Are dogs just like us?

    PubMed

    Gross, Michael

    2015-08-31

    Dogs have evolved to become the animal species most integrated with human society. Surprisingly, the origins and mechanisms of the remarkable co-evolution are still obscure and provide fuel for debates. Brain imaging studies showing up similarities and recent results implicating the hormone oxytocin also suggest that it makes sense to compare the social mind of dogs to our own. Michael Gross reports. PMID:26561653

  18. Why do adult dogs 'play'?

    PubMed

    Bradshaw, John W S; Pullen, Anne J; Rooney, Nicola J

    2015-01-01

    Among the Carnivora, play behaviour is usually made up of motor patterns characteristic of predatory, agonistic and courtship behaviour. Domestic dogs are unusual in that play is routinely performed by adults, both socially, with conspecifics and with humans, and also asocially, with objects. This enhanced playfulness is commonly thought to be a side effect of paedomorphosis, the perpetuation of juvenile traits into adulthood, but here we suggest that the functions of the different types of play are sufficiently distinct that they are unlikely to have arisen through a single evolutionary mechanism. Solitary play with objects appears to be derived from predatory behaviour: preferred toys are those that can be dismembered, and a complex habituation-like feedback system inhibits play with objects that are resistant to alteration. Intraspecific social play is structurally different from interspecific play and may therefore be motivationally distinct and serve different goals; for example, dogs often compete over objects when playing with other dogs, but are usually more cooperative when the play partner is human. The majority of dogs do not seem to regard competitive games played with a human partner as "dominance" contests: rather, winning possession of objects during games appears to be simply rewarding. Play may be an important factor in sociality, since dogs are capable of extracting social information not only from games in which they participate, but also from games that they observe between third parties. We suggest that the domestic dog's characteristic playfulness in social contexts is an adaptive trait, selected during domestication to facilitate both training for specific purposes, and the formation of emotionally-based bonds between dog and owner. Play frequency and form may therefore be an indicator of the quality of dog-owner relationships. PMID:25251020

  19. The Epigenetic Landscape of Mammary Gland Development and Functional Differentiation

    PubMed Central

    Rijnkels, Monique; Kabotyanski, Elena; Montazer-Torbati, Mohamad B.; Beauvais, C. Hue; Vassetzky, Yegor; Rosen, Jeffrey M.; Devinoy, Eve

    2010-01-01

    Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conformation initiated by DNA methylation, histone variants, post-translational modifications of histones, non-histone chromatin proteins, and non-coding RNAs. Epigenetics plays a key role in development. However, very little is known about its role in the developing mammary gland or how it might integrate the many signalling pathways involved in mammary gland development and function that have been discovered during the past few decades. An inverse relationship between marks of closed (DNA methylation) or open chromatin (DnaseI hypersensitivity, certain histone modifications) and milk protein gene expression has been documented. Recent studies have shown that during development and functional differentiation, both global and local chromatin changes occur. Locally, chromatin at distal regulatory elements and promoters of milk protein genes gains a more open conformation. Furthermore, changes occur both in looping between regulatory elements and attachment to nuclear matrix. These changes are induced by developmental signals and environmental conditions. Additionally, distinct epigenetic patterns have been identified in mammary gland stem and progenitor cell sub-populations. Together, these findings suggest that epigenetics plays a role in mammary development and function. With the new tools for epigenomics developed in recent years, we now can begin to establish a framework for the role of epigenetics in mammary gland development and disease. PMID:20157770

  20. Secondhand Tobacco Smoke Exposure and Lung Adenocarcinoma In Situ/Minimally Invasive Adenocarcinoma (AIS/MIA).

    PubMed

    Kim, Claire H; Lee, Yuan-Chin Amy; Hung, Rayjean J; Boffetta, Paolo; Xie, Dong; Wampfler, Jason A; Cote, Michele L; Chang, Shen-Chih; Ugolini, Donatella; Neri, Monica; Le Marchand, Loic; Schwartz, Ann G; Morgenstern, Hal; Christiani, David C; Yang, Ping; Zhang, Zuo-Feng

    2015-12-01

    The aim of this study was to estimate the effect of exposure to secondhand tobacco smoke on the incidence of lung adenocarcinoma in situ/minimally invasive adenocarcinoma (AIS/MIA). Data from seven case-control studies participating in the International Lung Cancer Consortium (ILCCO) were pooled, resulting in 625 cases of AIS/MIA and 7,403 controls, of whom 170 cases and 3,035 controls were never smokers. Unconditional logistic regression was used to estimate adjusted ORs (ORadj) and 95% confidence intervals (CI), controlling for age, sex, race, smoking status (ever/never), and pack-years of smoking. Study center was included in the models as a random-effects intercept term. Ever versus never exposure to secondhand tobacco smoke was positively associated with AIS/MIA incidence in all subjects (ORadj = 1.48; 95% CI, 1.14-1.93) and in never smokers (ORadj = 1.45; 95% CI, 1.00-2.12). There was, however, appreciable heterogeneity of ORadj across studies (P = 0.01), and the pooled estimates were largely influenced by one large study (40% of all cases and 30% of all controls). These findings provide weak evidence for an effect of secondhand tobacco smoke exposure on AIS/MIA incidence. Further studies are needed to assess the impact of secondhand tobacco smoke exposure using the newly recommended classification of subtypes of lung adenocarcinoma. PMID:26503035

  1. Periductal mastitis and mammary duct ectasia in a male.

    PubMed Central

    Ashworth, M. T.; Corcoran, G. D.; Haqqani, M. T.

    1985-01-01

    A case of periductal mastitis and mammary duct ectasia is presented in a 50 year old male, with presenting symptoms similar to those of females, namely subareolar breast lump and mastalgia. As far as can be ascertained only 4 cases of mammary duct ectasia and periductal mastitis in males have been reported previously. Since this entity is not well known in males it is possible that it may be underdiagnosed or misdiagnosed clinically and histologically. Images Figure 1 Figure 2 Figure 3 PMID:4040633

  2. Polyurethane-covered mammary implants: a 12-year experience.

    PubMed

    Gasperoni, C; Salgarello, M; Gargani, G

    1992-10-01

    Polyurethane-covered mammary implants are the implants of choice in aesthetic and reconstructive mammary surgery. These implants give very good results in regard to breast contour and consistency, and have a very low complication rate. We present our 12-year experience using polyurethane-covered prostheses. We place the implant mostly in the subglandular or subcutaneous site, and their capsular contracture rate is extremely low (3.3%). Based on our experience, we also review the other complications and side effects occurring with polyurethane prostheses and discuss them in detail. PMID:1466525

  3. Cadherin Cell Adhesion System in Canine Mammary Cancer: A Review

    PubMed Central

    Gama, Adelina; Schmitt, Fernando

    2012-01-01

    Cadherin-catenin adhesion complexes play important roles by providing cell-cell adhesion and communication in different organ systems. Abnormal expression of cadherin adhesion molecules constitutes a common phenomenon in canine mammary cancer and has been frequently implicated in tumour progression. This paper summarizes the current knowledge on cadherin/catenin adhesion molecules (E-cadherin, β-catenin, and P-cadherin) in canine mammary cancer, focusing on the putative biological functions and clinical significance of these molecules in this disease. This paper highlights the need for further research studies in this setting in order to elucidate the role of these adhesion molecules during tumour progression and metastasis. PMID:22973534

  4. [Physiology of secretory cells in the mouse mammary gland].

    PubMed

    Tolkunov, Iu A; Markov, A G

    2000-08-01

    Secretory cells' membrane potential and transepithelial potential difference in the mouse mammary gland diminish within 2.5 hours following breast-feeding of the litter. The transepithelial resistance for up to 20 hours after the feeding did not drop below 40-70 k omega. The secret pressure in the mammary gland does not grow during this period. Therefore an increase of interval between litter feeding up to 20 hours does not entail any mechanical lesion of the secretory epithelium. The latter's cells seem to secrete organic and inorganic substances in concentrations which do not change significantly during their transfer along the outgoing ducts. PMID:11059022

  5. Coronary bypass using bilateral internal mammary arteries in an achondroplast.

    PubMed

    Alassal, Mohamed Abdulwahab; Youssef, Mostafa; Koudieh, Mohammed

    2015-01-01

    Coronary bypass grafting for ischemic heart disease in achondroplastic dwarfs is very rare. Shortage of veins and inadequate vein quality may cause difficulties during surgery. Only 2 cases of coronary bypass surgery in an achondroplastic dwarf, in which the left internal mammary artery and vein grafts were used, have been reported. We describe the case of a 55-year-old male achondroplastic dwarf who had triple-vessel coronary disease and underwent successful coronary bypass surgery using one saphenous vein graft and bilateral internal mammary artery grafts. The anatomic and surgical challenges in achondroplasia are highlighted. PMID:24887865

  6. Mammary-type myofibroblastoma with the nephrotic syndrome

    PubMed Central

    Vankawala, Preksha; Kuperman, Michael B.; Mennel, Robert G.

    2016-01-01

    We describe a 23-year-old white man who presented with anasarca and a new periumbilical mass. He had preserved kidney function and laboratory findings consistent with nephrotic syndrome, including 9.7 g/day albuminuria. Serum serologies were positive for anti-SSa and anti-SSb and low complements but were negative for antinuclear antibody. Pathologic findings of the abdominal mass showed a mammary-type myofibroblastoma. A kidney biopsy revealed a diffuse proliferative and membranous immune-mediated glomerulonephritis with 10% interstitial fibrosis. This is a novel case of mammary-type myofibroblastoma associated with nephrotic syndrome mimicking a proliferative lupus pattern. PMID:27365885

  7. Modeling mammary gland morphogenesis as a reaction-diffusion process.

    PubMed

    Grant, Mark R; Hunt, C Anthony; Xia, Lan; Fata, Jimmie E; Bissell, Mina J

    2004-01-01

    Mammary ducts are formed through a process of branching morphogenesis. We present results of experiments using a simulation model of this process, and discuss their implications for understanding mammary duct extension and bifurcation. The model is a cellular automaton approximation of a reaction-diffusion process in which matrix metalloproteinases represent the activator, inhibitors of matrix metalloproteinases represent the inhibitor, and growth factors serve as a substrate. We compare results from the simulation model with those from in-vivo experiments as part of an assessment of whether duct extension and bifurcation during morphogenesis may be a consequence of a reaction-diffusion mechanism mediated by MMPs and TIMPs. PMID:17271768

  8. Radiogenic neoplasia in thyroid and mammary clonogens

    SciTech Connect

    Clifton, K.H.

    1992-05-20

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process.

  9. Hydrated nucleus pulposus herniation in seven dogs.

    PubMed

    Manunta, M L; Evangelisti, M A; Bergknut, N; Grinwis, G C M; Ballocco, I; Meij, B P

    2015-03-01

    The clinical signs, magnetic resonance imaging (MRI) findings, treatment and follow-up in seven dogs with hydrated nucleus pulposus extrusion (HNPE) are reported. All dogs had tetraparesis or tetraplegia. T2-weighted MRI revealed extradural hyperintense homogeneous material compressing the cervical spinal cord. After conservative treatment (five dogs) or surgical decompression (two dogs), all dogs returned to ambulatory function within 1 month. Follow-up MRI in conservatively treated dogs revealed complete disappearance of the extruded material. Histopathological examination of surgical specimens confirmed that the retrieved material was extruded nucleus pulposus with evidence of early degeneration. PMID:25599897

  10. Bilateral breast adenocarcinomas with EML4–ALK fusion in a patient with multiple metastases successfully treated with crizotinib: is lung the primary site?

    PubMed Central

    Liu, Chao; Ding, Lijuan; Sun, Bing; Wu, Shikai

    2016-01-01

    Breast metastases from non-mammary cancers are rare, especially when they appear synchronously. Clinically, it is vitally important to accurately diagnose these patients, as this will directly influence their treatment and survival. We present a very rare and complex case of bilateral breast adenocarcinomas with an EML4–ALK fusion, which was diagnosed as bilateral breast metastases of non-small-cell lung cancer by immunohistochemistry and comprehensive genomic investigation. The patient was successfully treated with an ALK inhibitor (crizotinib); symptoms improved quickly after initiation of crizotinib therapy, and a partial response was observed after 3 months. The experience of diagnosis and treatment of this case indicates the importance and necessity of genomic investigations in such patients, and suggests that we need to consider the rare possibility of this kind of metastasis in order to provide optimal treatment. PMID:27366096

  11. A human gallbladder adenocarcinoma cell line.

    PubMed

    Morgan, R T; Woods, L K; Moore, G E; McGavran, L; Quinn, L A; Semple, T U

    1981-06-01

    A continuous cell line, COLO 346, was established from a liver metastasis in a patient with adenocarcinoma of the gallbladder. COLO 346 grew as an adherent monolayer of pleomorphic epithelioid cells. COLO 346 cells produced esterone, but no estradiol, progesterone, or cortisol. No adrenocorticotropic hormones, beta-subunit of human chorionic gonadotropin, carcinoembryonic antigen, or alpha-fetoprotein production by the cells was detected. Cell doubling time was 36 h. Seven allelic isozymes were assayed. COLO 346 had a chromosome mode of 74 at 21 months postestablishment with 6 marker chromosomes present in 100% of the cells analyzed. COLO 346 has been in continuous culture for over 2 yr and is available to other investigators for their studies. PMID:7262900

  12. Clear cell adenocarcinoma arising from adenomyosis.

    PubMed

    Hirabayashi, Kenichi; Yasuda, Masanori; Kajiwara, Hiroshi; Nakamura, Naoya; Sato, Shigeru; Nishijima, Yoshihiro; Mikami, Mikio; Osamura, Robert Yoshiyuki

    2009-05-01

    A 73-year-old postmenopausal Japanese woman presented with a complaint of slight fever and weight loss. An elevated level of CA125 in the blood favored a diagnosis of malignant uterine body tumor, but was not confirmed by endometrial cytology and biopsy. Resection of the uterus revealed a solid whitish tumor in the myometrium that was diagnosed as clear cell adenocarcinoma (CCA) arising from adenomyosis. There were transitions between endometrial epithelium of adenomyosis, noninvasive CCA, and invasive CCA. Immunohistochemical expression of hepatocyte nuclear factor-1beta supported the diagnosis of CCA. Only one other English language document pertaining to CCA arising from adenomyosis exists. Malignant tumor arising from adenomyosis should be considered as a differential diagnosis when the serum level of tumor markers such as CA125 is high and when the tumor is intramyometrial. PMID:19620944

  13. Targeting cancer cell metabolism in pancreatic adenocarcinoma

    PubMed Central

    Cohen, Romain; Neuzillet, Cindy; Tijeras-Raballand, Annemilaï; Faivre, Sandrine; de Gramont, Armand; Raymond, Eric

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer death by 2030. Current therapeutic options are limited, warranting an urgent need to explore innovative treatment strategies. Due to specific microenvironment constraints including an extensive desmoplastic stroma reaction, PDAC faces major metabolic challenges, principally hypoxia and nutrient deprivation. Their connection with oncogenic alterations such as KRAS mutations has brought metabolic reprogramming to the forefront of PDAC therapeutic research. The Warburg effect, glutamine addiction, and autophagy stand as the most important adaptive metabolic mechanisms of cancer cells themselves, however metabolic reprogramming is also an important feature of the tumor microenvironment, having a major impact on epigenetic reprogramming and tumor cell interactions with its complex stroma. We present a comprehensive overview of the main metabolic adaptations contributing to PDAC development and progression. A review of current and future therapies targeting this range of metabolic pathways is provided. PMID:26164081

  14. Adenocarcinoma of the pigmented ciliary epithelium

    PubMed Central

    Sukeda, Aoi; Mori, Taisuke; Suzuki, Shigenobu; Ochiai, Atsushi

    2014-01-01

    Adenocarcinoma of the pigmented ciliary epithelium is an exceptionally rare eye tumour, with only a few cases reported to date. We encountered such a case in a 50-year-old woman who reported seeing floaters in her right eye. Fundus examination and MRI revealed an elevated lesion located in the ciliary body compressing the lens. The ciliary body was resected under the diagnosis of ciliary adenoma. On histological examination, the tumour exhibited epithelial features with glandular formation and moderate nuclear pleomorphism. The tumour invaded the subepithelial stroma of the ciliary body. Immunohistochemical findings were positive for cytokeratin OSCAR, AE1/AE3, CK7, EMA, S100, Melan A, HMB45, and microphthalmia-associated transcription factor. PMID:25015166

  15. Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

    NASA Astrophysics Data System (ADS)

    Cruz-Monserrate, Zobeida; Roland, Christina L.; Deng, Defeng; Arumugam, Thiruvengadam; Moshnikova, Anna; Andreev, Oleg A.; Reshetnyak, Yana K.; Logsdon, Craig D.

    2014-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.

  16. Apoptotic pathways in pancreatic ductal adenocarcinoma

    PubMed Central

    Hamacher, Rainer; Schmid, Roland M; Saur, Dieter; Schneider, Günter

    2008-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes of cancer related death. Despite the advances in understanding of the molecular pathogenesis, pancreatic cancer remains a major unsolved health problem. Overall, the 5-year survival rate is less than 5% demonstrating the insufficiency of current therapies. Most cytotoxic therapies induce apoptosis and PDAC cells have evolved a plethora of molecular mechanisms to assure survival. We will present anti-apoptotic strategies working at the level of the death receptors, the mitochondria or involving the caspase inhibitors of the IAP family. Furthermore, the survival function of the phosphotidylinositol-3' kinase (PI3K)/AKT- and NF-kappaB-pathways are illustrated. A detailed molecular knowledge of the anti-apoptotic mechanisms of PDAC cells will help to improve therapies for this dismal disease and therapeutic strategies targeting the programmed cell death machinery are in early preclinical and clinical development. PMID:18652674

  17. Effect of anthralin on cell viability in human prostate adenocarcinoma.

    PubMed

    Raevskaya, A A; Gorbunova, S L; Savvateeva, M V; Severin, S E; Kirpichnikov, M P

    2012-07-01

    The study revealed the key role of serine protease hepsin activity in transition of in situ prostate adenocarcinoma into the metastasizing form. Inhibition of hepsin activity suppresses the invasive growth of the tumor. Hepsin is an convenient target for pharmacological agents, so the study of its inhibitory mechanisms is a promising avenue in drug development. Assay of proteolytic activity in various tumor cell lines in vitro showed that this activity in prostate adenocarcinoma cells significantly surpasses proteolytic activity in other examined tumor cell lines. Selective cytotoxic action of anthralin, an inhibitor of hepsin activity, on human adenocarcinoma cells was demonstrated in comparison with other tumor cell lines. PMID:22866312

  18. The mammary glands of the Amazonian manatee, Trichechus inunguis (Mammalia: Sirenia): morphological characteristics and microscopic anatomy.

    PubMed

    Rodrigues, Fernanda Rosa; da Silva, Vera Maria Ferreira; Barcellos, José Fernando Marques

    2014-08-01

    The mammaries from carcasses of two female Amazonian manatees were examined. Trichechus inunguis possesses two axillary mammaries beneath the pectoral fins, one on each side of the body. Each papilla mammae has a small hole on its apex--the ostium papillare. The mammaries are covered by a stratified squamous keratinized epithelium. The epithelium of the mammary ducts became thinner more deeply in the tissue and varied from stratified to simple cuboidal. There was no evidence of glandular activity or secretion into the ducts of the mammary glands. PMID:24920139

  19. 9 CFR 93.600 - Importation of dogs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Importation of dogs. 93.600 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Dogs § 93.600 Importation of dogs. (a) All dogs. Dogs from any region of...) Dogs must be accompanied by a certificate signed by a full-time salaried veterinary official of...

  20. 9 CFR 93.600 - Importation of dogs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Importation of dogs. 93.600 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Dogs § 93.600 Importation of dogs. (a) All dogs. Dogs from Angola... applicable requirements of this part: (1) Dogs must be accompanied by a certificate signed by a...

  1. 9 CFR 93.600 - Importation of dogs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Importation of dogs. 93.600 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Dogs § 93.600 Importation of dogs. (a) All dogs. Dogs from Angola... applicable requirements of this part: (1) Dogs must be accompanied by a certificate signed by a...

  2. 9 CFR 93.600 - Importation of dogs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Importation of dogs. 93.600 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Dogs § 93.600 Importation of dogs. (a) All dogs. Dogs from any region of...) Dogs must be accompanied by a certificate signed by a full-time salaried veterinary official of...

  3. 9 CFR 93.600 - Importation of dogs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Importation of dogs. 93.600 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Dogs § 93.600 Importation of dogs. (a) All dogs. Dogs from Angola... applicable requirements of this part: (1) Dogs must be accompanied by a certificate signed by a...

  4. Adenocarcinoma of the anal canal: A report of two cases with review of literature.

    PubMed

    Kulkarni, Medha Pradip; Momin, Yasmin Altaf; Pandav, Amitkumar Bapuso; Sulhyan, Kalpana Ranjitsingh

    2016-01-01

    Adenocarcinoma of the anal canal accounts for about 20% of all anal canal cancers. It is subclassified into two types. (1) Colorectal type, which arises from the mucosa above dentate line and (2) extramucosal type, which includes adenocarcinoma arising in anorectal fistulae and adenocarcinoma arising from anal glands. Anal gland adenocarcinomas are extremely rare. In this article, we present two cases of anal adenocarcinoma, one colorectal type, and other anal gland carcinoma along with review of literature. PMID:27510691

  5. An in vitro model of epithelial cell growth stimulation in the rodent mammary gland.

    PubMed

    Ehmann, U K; DeVries, J T; Chen, M S C; Adamos, A A; Guzman, R C; Omary, M B

    2003-08-01

    Mouse mammary epithelial cell cultures previously described bring about extensive proliferation and a cell population with the appropriate markers for luminal ductal epithelial cells, and also the ability to form normal tissue after implantation into mice. This success may result from a culture environment that resembles certain aspects of the environment in the mammary gland. Mouse mammary epithelial cells, whose proliferation is limited when plated alone, can be stimulated to multiply by contact with lethally irradiated cells of the LA7 rat mammary tumour line. Most of the proliferative stimulus is imparted by direct cell contact between LA7 and mouse mammary cells. Junctions, including adherens junctions, form among all cells in the culture, much as junctions form in the mammary gland. LA7 cells secrete TGFalpha and bFGF, factors found in the mammary gland, and factors to which mouse mammary cells respond in culture. Mouse mammary cells express keratins 8 and 18, markers for luminal cells of the mammary duct. LA7 cells express keratin 14 and vimentin, markers for myoepithelial cells. These facts, taken together, fit a model of cell replacement in an epithelial tissue and also imitate the relationship between luminal ductal cells and myoepithelial cells in the mammary gland. This method of culturing cells is useful, not only for in vitro-in vivo carcinogenesis studies, but also for the study of mechanisms by which growth signals are imparted from one cell to another. PMID:12950387

  6. Effect of tunicamycin on sialomucin and natural killer susceptibility of rat mammary tumor ascites cells.

    PubMed

    Bharathan, S; Moriarty, J; Moody, C E; Sherblom, A P

    1990-09-01

    The MAT-B1 and MAT-C1 ascites sublines of the 13762 rat mammary adenocarcinoma contain a dominant cell surface "complex" consisting of two glycoproteins: ascites sialoglycoprotein (ASGP)-1, a Mr 600,000-700,000 peanut agglutinin-binding sialomucin, and ASGP-2, a Mr 120,000 concancavalin A-binding glycoprotein (Sherblom et al., J. Biol. Chem., 255: 783-790, 1980; Sherblom and Carraway, J. Biol. Chem., 255: 12051-12059, 1980). Although both cell lines are resistant to lysis by natural killer cells, treatments which result in loss of cell surface ASGP-1 render the cells susceptible to natural killer cell lysis (Sherblom and Moody, Cancer Res., 46:4543-4546, 1986). Treatment of the ascites cells with 5 micrograms/ml tunicamycin for 24 h effectively inhibits glycosylation of ASGP-2 without affecting cell viability or total protein synthesis. Under these conditions, expression of ASGP-1 is depressed by at least 50% in both cell lines, as monitored by [3H]glucosamine incorporation and by binding of peanut agglutinin to intact cells. The size distribution of O-linked oligosaccharides in ASGP-1 from tunicamycin-treated versus control MAT-B1 cells is indistinguishable, as determined by Bio-Gel P-4 chromatography following alkaline-borohydride treatment. Complex isolated from either treated or control cells bands at the same density in a CsCl gradient containing Triton X-100 and contains a diffuse band corresponding to ASGP-2 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tunicamycin-treated cells, consistent with the reduced expression of ASGP-1, are significantly more susceptible to natural killer cell-mediated lysis, when compared to untreated controls. The results suggest that N-linked glycosylation is a prerequisite for sialomucin synthesis and/or complex formation. PMID:2386935

  7. Diet-induced obesity disrupts ductal development in the mammary glands of nonpregnant mice.

    PubMed

    Kamikawa, Akihiro; Ichii, Osamu; Yamaji, Daisuke; Imao, Takeshi; Suzuki, Chiharu; Okamatsu-Ogura, Yuko; Terao, Akira; Kon, Yasuhiro; Kimura, Kazuhiro

    2009-05-01

    Mammary glands develop postnatally in response to the hypothalamic-pituitary-gonadal axis. Obesity-induced changes in the local environment, however, retard mammary gland development during late pregnancy and lactation. To clarify the effects of obesity on fundamental duct development, we compared the mammary glands of nulliparous nonpregnant obese mice fed a high-fat diet with those of lean mice fed a normal diet. Obese mice had enlarged mammary glands, reflecting fat pad size, whereas the ducts in obese mice showed a less dense distribution with less frequent branching. Additionally, the ducts were surrounded by thick collagen layers, and were incompletely lined with myoepithelium. Because leptin receptors were localized in the epithelium region and leptin that was highly expressed in the obese glands suppressed mammary epithelial cell proliferation in vitro, the present results suggest that obesity disrupts mammary ductal development, possibly by remodeling the mammary microenvironment and promoting the expression of such paracrine factors as leptin. PMID:19384959

  8. [Dangerous dogs in Berlin in comparison to the dog population--ways to reduce the dangerousness of dogs].

    PubMed

    Kuhne, Franziska; Struwe, Rainer

    2006-01-01

    The law for handling and control of dogs in Berlin of September 29, 2004 was enacted to prevent the risks for humans and animals when ever they have contact with dogs. "Dangerous dogs" are defined by this law. There are 10 breeds of dogs supposed to be dangerous due to specific characteristics of their breed ("listed breeds"). The dangerousness of a dog's breed is not identical with the dangerousness of an individual dog. The subject of this study is to examine the potential dangerousness of dog breeds and not the individual dangerousness of a dog. This study refers to statistics of incidents between dogs and humans in Berlin for the years 1998 to 2004. The population density of a breed is based on the dogs assessed for tax purposes in Berlin of January 1, 2005 and on the dog registrations maintained at veterinary hospitals. The fourfold-table-test was used to compare the quantity of the recorded incidents of two statistically independent dog breeds. Of the total population of 107,804 tax assessed dogs in Berlin in 2004, 0.9% was documented as dogs involved in incidents with humans. The incidents per year decreased in the "listed breeds"about 68% and in the "unlisted breeds" about 41% during the last 7 years in Berlin. Therefore, the probability (the odds ratio) of a breed to be conspicuous was analysed. The values for the calculation of this probability were the number of dogs of a breed having been involved in incidents compared to the population of this breed based on tax records. The comparison of the probability of a breed with another to be conspicuous was used to compile a cluster of breeds which had the same probability to be conspicuous in 2004. A cluster was assessed for dogs of the following breeds: Sheep dogs, Rottweiler, Doberman, Pitbull Terrier and American Staffordshire Terrier. A listing of breeds is not the right way to reduce the potential dangerousness of a dog, especially in the private domain of their owners. Most incidents with dogs occur in

  9. Quantification of mammary organoid toxicant response and mammary tissue motility using OCT fluctuation spectroscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Yu, Xiao; Blackmon, Richard L.; Carabas-Hernendez, Patricia; Fuller, Ashley; Troester, Melissa A.; Oldenburg, Amy L.

    2016-03-01

    Mammary epithelial cell (MEC) organoids in 3D culture recapitulate features of breast ducts in vivo. OCT has the ability to monitor the evolution of MEC organoids non-invasively and longitudinally. The anti-cancer drug Doxorubicin (Dox) is able to inhibit proliferation of cancer cells and has been widely used for chemotherapy of breast cancers; while environmental toxins implicated in breast cancer such as estrogen regulates mammary tumor growth and stimulates the proliferation and metastatic potential of breast cancers. Here we propose a quantitative method for measuring motility of breast cells in 3D cultures based upon OCT speckle fluctuation spectroscopy. The metrics of the inverse power-law exponent (α) and fractional modulation amplitude (M) were extracted from speckle fluctuation spectra. These were used to quantify the responses of MEC organoids to Dox, and estrogen. We investigated MEC organoids comprised of two different MEC lines: MCF10DCIS.com exposed to Dox, and MCF7 exposed to estrogen. We found an increase (p<0.001) in α of MEC along time (t=0, 1 hour, 24 hours, 48 hours and 6 days) at each dose of Dox (0, 1 μM and 10 μM), indicating lower fluctuation intensity at higher frequencies. We also observed a decrease (p<0.001) in M for increasing time. However, both α and M of MCF7 treated with estrogen (0, 1 nM and 10 nM) exhibited the opposite trend along time. This novel technology provides rapid and non-invasive measurements of the effects of toxicants on MEC motility for understanding breast cancer development and assessing anti-cancer drugs.

  10. Assisting Handlers Following Attacks on Dog Guides: Implications for Dog Guide Teams

    ERIC Educational Resources Information Center

    Godley, Cheryl A.; Gillard, Marc A.

    2011-01-01

    Attacks by dogs on dog guides are traumatic for dog guide teams. One variable that affects a team's recovery is how handlers cope with emotional responses to the attack. This article presents a three-stage model for assisting handlers that is useful for handlers and dog guide instructors.

  11. Angiosarcoma of the Prostate Gland following Brachytherapy for Prostatic Adenocarcinoma

    PubMed Central

    Gupta, Arjun; Patnaik, Mrinal M.; Naina, Harris V.

    2015-01-01

    Prostatic adenocarcinoma is the most common cancer in men, but only a handful of cases of prostatic angiosarcoma have been reported in the literature. Prior radiation therapy for prostatic adenocarcinoma has been hypothesized to be a risk factor for angiosarcoma. The increasing practice of prostate cancer screening and the use of radiation therapy for management of prostatic adenocarcinoma will likely lead to more cases of prostatic angiosarcoma. Diagnosis is made by tissue sampling. Optimal management of these aggressive tumors remains to be defined and outcomes are poor with a high 1-year mortality. Primary care physicians and urologists should be aware of this rare entity and refer these patients to specialist centers where they can be managed by a multidisciplinary team. We report a case of angiosarcoma of the prostate gland diagnosed in a male presenting with lower urinary tract symptoms 5 years after brachytherapy for prostate adenocarcinoma. PMID:26889128

  12. Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas

    ClinicalTrials.gov

    2014-03-28

    Adenocarcinoma of the Pancreas; Advanced Solid Tumors; Cancer; Cancer of Pancreas; Cancer of the Pancreas; Metastases; Metastatic Cancer; Metastatic Pancreatic Cancer; Pancreas Cancer; Pancreatic Cancer; Bone Metastases; Endocrine Cancer; Oncology; Oncology Patients; Solid Tumors; Advanced Malignancy

  13. Plasma Creatinine Clearance in the Dog

    ERIC Educational Resources Information Center

    Frazier, Loy W.

    1977-01-01

    Lists materials and methods for an experiment that demonstrates the concept of glomerular filtration rate (GFR) using anesthesized dogs. In the dog, GFR is equivalent to the renal plasma clearance of exogenous creatinine. (CS)

  14. [Imported infestations of nasopharyngeal parasites in dogs].

    PubMed

    Gothe, R; Barutzki, D; Schöl, H; Heinen, H

    1991-02-01

    In this paper infestations of the nasal cavity with Myxobdella annandalei in a dog after a sojourn in Nepal and with Linguatula serrata in 2 stray dogs from Turkey, which were imported to Germany, are described. PMID:2048114

  15. Extradural spinal synovial cysts in nine dogs.

    PubMed

    Dickinson, P J; Sturges, B K; Berry, W L; Vernau, K M; Koblik, P D; Lecouteur, R A

    2001-10-01

    Nine dogs presenting for investigation of cervical or thoracolumbar myelopathies were diagnosed with extradural spinal synovial cysts. Degenerative disease affecting the articular facets or intervertebral discs was present on plain spinal radiographs in all cases. Myelography was consistent with dorsolateral, extradural spinal cord compression. Two groups of dogs were identified: (1) young, giant breed dogs with multiple cysts involving one or more levels of the cervical spinal cord; and (2) older, large breed dogs with solitary cysts involving the thoracolumbar spinal cord. The synovial cysts constituted the major compressive lesions in four of the dogs. Analysis of lumbar cerebrospinal fluid demonstrated albuminocytological dissociation, consistent with chronic compressive myelopathy, in six dogs. All dogs underwent decompressive surgery and the diagnosis of synovial cysts was confirmed histologically. The mean follow-up period was 17 months (range four to 36 months). At the time of follow-up, all dogs were fully ambulatory with improved neurological function compared with that at initial presentation. PMID:11688527

  16. Military Dog Training for Law Enforcement

    ERIC Educational Resources Information Center

    Atwell, Lou E.

    1977-01-01

    Describes five courses involved in the intensive training that dogs and their handlers go through in the Military Dog Studies Branch at Lackland Air Force Base (San Antonio, Texas) in preparation for duties in law enforcement. (HD)

  17. Dog allergen levels in homes with hypoallergenic compared with nonhypoallergenic dogs

    PubMed Central

    Wegienka, Ganesa R.; Havstad, Suzanne L.; Zoratti, Edward M.; Ownby, Dennis R.; Johnson, Christine Cole

    2011-01-01

    Background: Despite the public interest in hypoallergenic dogs, few scientific, including epidemiological studies have attempted to evaluate claims of hypoallergenicity. This study was designed to determine whether dog breeds reported as hypoallergenic correspond to lower dog allergen in the home versus nonhypoallergenic dogs. Methods: A web search was conducted to identify breeds cited as hypoallergenic. Four separate classification schemes using combinations of purebred and mixed breed dogs were used to compare the levels of Canis familiaris 1 in dust samples collected from homes with hypoallergenic versus nonhypoallergenic dogs from an established birth cohort. Results: No classification scheme showed that the level of dog allergen in homes with hypoallergenic dogs differed from other homes. Conclusion: Dog-allergic individuals should have access to scientifically valid information on the level of allergen shedding of different breeds of dogs. PMID:21819763

  18. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  19. Selective transport of IgE into ovine mammary secretions.

    PubMed

    Hine, B C; Hunt, P W; Beasley, A M; Windon, R G; Glover, S A; Colditz, I G

    2010-10-01

    Immunoglobulin (Ig) E is actively transported into ovine colostrum. Here we examine the degree of selectivity and the mechanism by which this transfer occurs in sheep. Results indicate that during colostrogenesis in sheep, transfer of immunoglobulins was most selective for IgG1 and IgA followed by IgE, IgM and IgG2. In milk, selectivity was greatest for IgA, followed by IgM, IgE, IgG1 and IgG2. The neonatal Fc receptor (FcRn) and poly immunoglobulin receptor (pIgR) mediate the transport of IgG1 and IgA across the ovine mammary epithelium respectively. In primates and rodents, the low-affinity IgE receptor, Fc epsilonRII, functions to transport IgE across the intestinal epithelium. We therefore investigated the expression of the low-affinity IgE receptor (CD23), pIgR and FcRn transcripts in the ovine mammary gland. The expression profiles of FcRn, pIgR and CD23 mRNA reflected concentrations of their Ig ligands in mammary secretions. These findings suggest a role for CD23 in transport of IgE across the mammary epithelium of sheep. PMID:20226487

  20. The dynamics of murine mammary stem/progenitor cells

    PubMed Central

    DONG, Qiaoxiang; SUN, Lu-Zhe

    2014-01-01

    The stem/progenitor cells in the murine mammary gland are a highly dynamic population of cells that are responsible for ductal elongation in puberty, homeostasis maintenance in adult, and lobulo-alveolar genesis during pregnancy. In recent years understanding the epithelial cell hierarchy within the mammary gland is becoming particularly important as these different stem/progenitor cells were perceived to be the cells of origin for various subtypes of breast cancer. Although significant advances have been made in enrichment and isolation of stem/progenitor cells by combinations of antibodies against cell surface proteins together with flow cytometry, and in identification of stem/progenitor cells with multi-lineage differentiation and self-renewal using mammary fat pad reconstitution assay and in vivo genetic labeling technique, a clear understanding of how these different stem/progenitors are orchestrated in the mammary gland is still lacking. Here we discuss the different in vivo and in vitro methods currently available for stem/progenitor identification, their associated caveats, and a possible new hierarchy model to reconcile various putative stem/progenitor cell populations identified by different research groups. PMID:25580105

  1. FEEDING GENISTEIN TO PREPUBERTAL GILTS STIMULATES THEIR MAMMARY DEVELOPMENT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The possible role of dietary genistein on mammary development of prepubertal gilts was investigated. Forty-five gilts were fed one of three diets from 90 d of age until slaughter (day 183 ± 1). Diets were: without soya (CTL0, n=15); soya-based commercial (CTLS, n=15); and soya-based commercial with ...

  2. Laminin Mediates Tissue-specific Gene Expression in Mammary Epithelia

    SciTech Connect

    Streuli, Charles H; Schmidhauser, Christian; Bailey, Nina; Yurchenco, Peter; Skubitz, Amy P. N.; Roskelley, Calvin; Bissell, Mina J

    1995-04-01

    Tissue-specific gene expression in mammary epithelium is dependent on the extracellular matrix as well as hormones. There is good evidence that the basement membrane provides signals for regulating beta-casein expression, and that integrins are involved in this process. Here, we demonstrate that in the presence of lactogenic hormones, laminin can direct expression of the beta-casein gene. Mouse mammary epithelial cells plated on gels of native laminin or laminin-entactin undergo functional differentiation. On tissue culture plastic, mammary cells respond to soluble basement membrane or purified laminin, but not other extracellular matrix components, by synthesizing beta-casein. In mammary cells transfected with chloramphenicol acetyl transferase reporter constructs, laminin activates transcription from the beta-casein promoter through a specific enhancer element. The inductive effect of laminin on casein expression was specifically blocked by the E3 fragment of the carboxy terminal region of the alpha 1 chain of laminin, by antisera raised against the E3 fragment, and by a peptide corresponding to a sequence within this region. Our results demonstrate that laminin can direct tissue-specific gene expression in epithelial cells through its globular domain.

  3. Pten in Stromal Fibroblasts Suppresses Mammary Epithelial Tumors

    PubMed Central

    Trimboli, Anthony J.; Cantemir-Stone, Carmen Z.; Li, Fu; Wallace, Julie A.; Merchant, Anand; Creasap, Nicholas; Thompson, John C.; Caserta, Enrico; Wang, Hui; Chong, Jean-Leon; Naidu, Shan; Wei, Guo; Sharma, Sudarshana M.; Stephens, Julie A.; Fernandez, Soledad A.; Gurcan, Metin N.; Weinstein, Michael B.; Barsky, Sanford H.; Yee, Lisa; Rosol, Thomas J.; Stromberg, Paul C.; Robinson, Michael L.; Pepin, Francois; Hallett, Michael; Park, Morag; Ostrowski, Michael C.; Leone, Gustavo

    2009-01-01

    SUMMARY The tumor stroma is believed to contribute to some of the most malignant characteristics of epithelial tumors. However, signaling between stromal and tumor cells is complex and remains poorly understood. Here we show that the genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands accelerated the initiation, progression and malignant transformation of mammary epithelial tumors. This was associated with the massive remodeling of the extra-cellular matrix (ECM), innate immune cell infiltration and increased angiogenesis. Loss of Pten in stromal fibroblasts led to increased expression, phosphorylation (T72) and recruitment of Ets2 to target promoters known to be involved in these processes. Remarkably, Ets2 inactivation in Pten stroma-deleted tumors ameliorated disruption of the tumor microenvironment and was sufficient to decrease tumor growth and progression. Global gene expression profiling of mammary stromal cells identified a Pten-specific signature that was highly represented in the tumor stroma of breast cancer patients. These findings identify the Pten-Ets2 axis as a critical stroma-specific signaling pathway that suppresses mammary epithelial tumors. PMID:19847259

  4. Mechanisms of suberoylanilide hydroxamic acid inhibition of mammary cell growth

    PubMed Central

    Said, Thenaa K; Moraes, Ricardo CB; Sinha, Raghu; Medina, Daniel

    2001-01-01

    The mechanism of suberoylanilide hydroxamic acid in cell growth inhibition involved induction of pRb-2/p130 interaction and nuclear translocation with E2F-4, followed by significant repression in E2F-1 and PCNA nuclear levels, which led to inhibition in DNA synthesis in mammary epithelial cell lines. PMID:11250759

  5. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol

    PubMed Central

    CRUZ, PAMELA; TORRES, CRISTIAN; RAMÍREZ, MARÍA EUGENIA; EPUÑÁN, MARÍA JOSÉ; VALLADARES, LUIS EMILIO; SIERRALTA, WALTER DANIEL

    2010-01-01

    The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E2) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E2, and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E2 in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E2-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels. PMID:22993572

  6. Precursors of hexoneogenesis within the human mammary gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The human mammary gland is capable of de novo synthesis of glucose and galactose (hexoneogenesis); however, the carbon source is incompletely understood. In this study, we investigated the role of acetate, glutamine, lactate and glycerol as potential carbon sources for hexoneogenesis. Healthy breast...

  7. Internal mammary sentinel lymph node biopsy: abandon or persist?

    PubMed Central

    Qiu, Peng-Fei; Liu, Yan-Bing; Wang, Yong-Sheng

    2016-01-01

    Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been little change in surgical practice patterns due to the low visualization rate of internal mammary sentinel lymph nodes with the traditional injection technique. Meanwhile, as internal mammary lymph nodes (IMLN) metastases are mostly found concomitantly with axillary lymph nodes (ALN) metastases, previous IM-SLNB clinical trials fail to evaluate the status of IMLN in patients who are really in need (only in clinically ALN negative patients). Our modified injection technique (periareolar intraparenchymal, high volume, and ultrasonographic guidance) significantly improved the visualization rate of internal mammary sentinel lymph nodes, making the routine IM-SLNB possible in daily practice. IM-SLNB could provide individual minimally invasive staging, prognosis, and decision-making for breast cancer patients, especially for patients with clinically positive ALN. Moreover, IMLN radiotherapy should be tailored and balanced between the potential benefit and toxicity, and IM-SLNB-guided IMLN radiotherapy could achieve this goal. In the era of effective adjuvant therapy, within the changing treatment approach – more systemic therapy, less loco-regional therapy – clinicians should deliberate the application of regional IMLN therapy. PMID:27390528

  8. Internal mammary sentinel lymph node biopsy: abandon or persist?

    PubMed

    Qiu, Peng-Fei; Liu, Yan-Bing; Wang, Yong-Sheng

    2016-01-01

    Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been little change in surgical practice patterns due to the low visualization rate of internal mammary sentinel lymph nodes with the traditional injection technique. Meanwhile, as internal mammary lymph nodes (IMLN) metastases are mostly found concomitantly with axillary lymph nodes (ALN) metastases, previous IM-SLNB clinical trials fail to evaluate the status of IMLN in patients who are really in need (only in clinically ALN negative patients). Our modified injection technique (periareolar intraparenchymal, high volume, and ultrasonographic guidance) significantly improved the visualization rate of internal mammary sentinel lymph nodes, making the routine IM-SLNB possible in daily practice. IM-SLNB could provide individual minimally invasive staging, prognosis, and decision-making for breast cancer patients, especially for patients with clinically positive ALN. Moreover, IMLN radiotherapy should be tailored and balanced between the potential benefit and toxicity, and IM-SLNB-guided IMLN radiotherapy could achieve this goal. In the era of effective adjuvant therapy, within the changing treatment approach - more systemic therapy, less loco-regional therapy - clinicians should deliberate the application of regional IMLN therapy. PMID:27390528

  9. The epigenetic landscape of mammary gland development and functional differentiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conf...

  10. Comparison of computed tomographic and pathologic findings in 17 dogs with primary adrenal neoplasia.

    PubMed

    Gregori, Tommaso; Mantis, Panagiotis; Benigni, Livia; Priestnall, Simon L; Lamb, Christopher R

    2015-01-01

    The CT appearance of canine adrenal masses has been reported, but associations between imaging features and pathologic features of these lesions have not been investigated in detail. The purpose of this study was to test associations between different types of adrenal neoplasia and their CT and pathologic features. A retrospective cross-sectional study was performed and inclusion criteria were histologic diagnosis of primary adrenal neoplasia, contrast-enhanced CT examination of the abdomen and surgical resection of the mass or necropsy examination. For all included dogs, CT images and histopathologic specimens were reviewed independently by two veterinary radiologists and a veterinary pathologist, respectively. Seventeen dogs met inclusion criteria. Diagnoses were adenocarcinoma in nine (53%) dogs, pheochromocytoma in five (29%) dogs, and adenoma in three (18%) dogs. Pheochromocytoma was associated with CT signs of vascular invasion (likelihood ratio = 4.8, 95% CI = 1.3-18.3, P = 0.03) and macroscopic vascular invasion (likelihood ratio = 9.6, 95% CI = 1.4-65.9, P = 0.02). There was excellent agreement between signs of vascular invasion in CT images and vascular invasion at surgery or necropsy (kappa = 0.86, P = 0.001). A peripheral contrast-enhancing rim in delayed postcontrast CT images was associated with fibrous encapsulation of the tumor (kappa = 0.53, P = 0.05), and a heterogeneous pattern of contrast distribution in delayed postcontrast CT images was associated with adrenal hemorrhage or infarction on histological examination (kappa = 0.45, P = 0.05). Findings indicated that CT enabled assessment of adrenal neoplasia features that reflected their biological behavior and pathological findings, however overlapping characteristics between tumor types limited the potential for reliably distinguishing them based on CT alone. PMID:25139015

  11. Three-Dimensional Cultures of Mouse Mammary Epithelial Cells

    PubMed Central

    Mroue, Rana; Bissell, Mina J.

    2013-01-01

    The mammary gland is an ideal “model organism” for studying tissue specificity and gene expression in mammals: it is one of the few organs that develop after birth and it undergoes multiple cycles of growth, differentiation and regression during the animal’s lifetime in preparation for the important function of lactation. The basic “functional differentiation” unit in the gland is the mammary acinus made up of a layer of polarized epithelial cells specialized for milk production surrounded by myoepithelial contractile cells, and the two-layered structure is surrounded by basement membrane. Much knowledge about the regulation of mammary gland development has been acquired from studying the physiology of the gland and of lactation in rodents. Culture studies, however, were hampered by the inability to maintain functional differentiation on conventional tissue culture plastic. We now know that the microenvironment, including the extracellular matrix and tissue architecture, plays a crucial role in directing functional differentiation of organs. Thus, in order for culture systems to be effective experimental models, they need to recapitulate the basic unit of differentiated function in the tissue or organ and to maintain its three-dimensional (3D) structure. Mouse mammary culture models evolved from basic monolayers of cells to an array of complex 3D systems that observe the importance of the microenvironment in dictating proper tissue function and structure. In this chapter, we focus on how 3D mouse mammary epithelial cultures have enabled investigators to gain a better understanding of the organization, development and function of the acinus, and to identify key molecular, structural, and mechanical cues important for maintaining mammary function and architecture. The accompanying chapter of Vidi et al. describes 3D models developed for human cells. Here, we describe how mouse primary epithelial cells and cell lines—essentially those we use in our

  12. DNA testing and domestic dogs.

    PubMed

    Mellersh, Cathryn

    2012-02-01

    There are currently about 80 different DNA tests available for mutations that are associated with inherited disease in the domestic dog, and as the tools available with which to dissect the canine genome become increasingly sophisticated, this number can be expected to rise dramatically over the next few years. With unrelenting media pressure focused firmly on the health of the purebred domestic dog, veterinarians and dog breeders are turning increasingly to DNA tests to ensure the health of their dogs. It is ultimately the responsibility of the scientists who identify disease-associated genetic variants to make sensible choices about which discoveries are appropriate to develop into commercially available DNA tests for the lay dog breeder, who needs to balance the need to improve the genetic health of their breed with the need to maintain genetic diversity. This review discusses some of the factors that should be considered along the route from mutation discovery to DNA test and some representative examples of DNA tests currently available. PMID:22071879

  13. 49 CFR 236.743 - Dog, swing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Dog, swing. 236.743 Section 236.743 Transportation... OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.743 Dog, swing. A locking dog mounted in such a manner that it is free to rotate on a trunnion which is riveted to a...

  14. 49 CFR 236.743 - Dog, swing.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Dog, swing. 236.743 Section 236.743 Transportation... OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.743 Dog, swing. A locking dog mounted in such a manner that it is free to rotate on a trunnion which is riveted to a...

  15. 50 CFR 216.82 - Dogs prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Dogs prohibited. 216.82 Section 216.82... Pribilof Islands Administration § 216.82 Dogs prohibited. In order to prevent molestation of fur seal herds, the landing of any dogs at Pribilof Islands is prohibited....

  16. 49 CFR 236.743 - Dog, swing.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Dog, swing. 236.743 Section 236.743 Transportation... OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.743 Dog, swing. A locking dog mounted in such a manner that it is free to rotate on a trunnion which is riveted to a...

  17. 50 CFR 216.82 - Dogs prohibited.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 10 2014-10-01 2014-10-01 false Dogs prohibited. 216.82 Section 216.82... Pribilof Islands Administration § 216.82 Dogs prohibited. In order to prevent molestation of fur seal herds, the landing of any dogs at Pribilof Islands is prohibited....

  18. 49 CFR 236.743 - Dog, swing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Dog, swing. 236.743 Section 236.743 Transportation... OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.743 Dog, swing. A locking dog mounted in such a manner that it is free to rotate on a trunnion which is riveted to a...

  19. 49 CFR 236.743 - Dog, swing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Dog, swing. 236.743 Section 236.743 Transportation... OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Definitions § 236.743 Dog, swing. A locking dog mounted in such a manner that it is free to rotate on a trunnion which is riveted to a...

  20. 50 CFR 216.82 - Dogs prohibited.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Dogs prohibited. 216.82 Section 216.82... Pribilof Islands Administration § 216.82 Dogs prohibited. In order to prevent molestation of fur seal herds, the landing of any dogs at Pribilof Islands is prohibited....

  1. 50 CFR 216.82 - Dogs prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Dogs prohibited. 216.82 Section 216.82... Pribilof Islands Administration § 216.82 Dogs prohibited. In order to prevent molestation of fur seal herds, the landing of any dogs at Pribilof Islands is prohibited....

  2. 50 CFR 216.82 - Dogs prohibited.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Dogs prohibited. 216.82 Section 216.82... Pribilof Islands Administration § 216.82 Dogs prohibited. In order to prevent molestation of fur seal herds, the landing of any dogs at Pribilof Islands is prohibited....

  3. Dipylidium (Dog and Cat Flea Tapeworm) FAQs

    MedlinePlus

    ... the most common kind of tapeworm dogs and cats get? The most common tapeworm of dogs and cats in the United States is called Dipylidium caninum . ... infected with a tapeworm larvae. A dog or cat may swallow a flea while self-grooming. Once ...

  4. Hendra Virus Infection in Dog, Australia, 2013.

    PubMed

    Kirkland, Peter D; Gabor, Melinda; Poe, Ian; Neale, Kristie; Chaffey, Kim; Finlaison, Deborah S; Gu, Xingnian; Hick, Paul M; Read, Andrew J; Wright, Therese; Middleton, Deborah

    2015-12-01

    Hendra virus occasionally causes severe disease in horses and humans. In Australia in 2013, infection was detected in a dog that had been in contact with an infected horse. Abnormalities and viral RNA were found in the dog's kidney, brain, lymph nodes, spleen, and liver. Dogs should be kept away from infected horses. PMID:26583697

  5. ATG proteins mediate efferocytosis and suppress inflammation in mammary involution

    PubMed Central

    Teplova, Irina; Lozy, Fred; Price, Sandy; Singh, Sukhwinder; Barnard, Nicola; Cardiff, Robert D.; Birge, Raymond B.; Karantza, Vassiliki

    2013-01-01

    Involution is the process of post-lactational mammary gland regression to quiescence and it involves secretory epithelial cell death, stroma remodeling and gland repopulation by adipocytes. Though reportedly accompanying apoptosis, the role of autophagy in involution has not yet been determined. We now report that autophagy-related (ATG) proteins mediate dead cell clearance and suppress inflammation during mammary involution. In vivo, Becn1+/− and Atg7-deficient mammary epithelial cells (MECs) produced ‘competent’ apoptotic bodies, but were defective phagocytes in association with reduced expression of the MERTK and ITGB5 receptors, thus pointing to defective apoptotic body engulfment. Atg-deficient tissues exhibited higher levels of involution-associated inflammation, which could be indicative of a tumor-modulating microenvironment, and developed ductal ectasia, a manifestation of deregulated post-involution gland remodeling. In vitro, ATG (BECN1 or ATG7) knockdown compromised MEC-mediated apoptotic body clearance in association with decreased RAC1 activation, thus confirming that, in addition to the defective phagocytic processing reported by other studies, ATG protein defects also impair dead cell engulfment.   Using two different mouse models with mammary gland-associated Atg deficiencies, our studies shed light on the essential role of ATG proteins in MEC-mediated efferocytosis during mammary involution and provide novel insights into this important developmental process. This work also raises the possibility that a regulatory feedback loop exists, by which the efficacy of phagocytic cargo processing in turn regulates the rate of engulfment and ultimately determines the kinetics of phagocytosis and dead cell clearance. PMID:23380905

  6. Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells

    SciTech Connect

    Hirai, H.; Lochter, A.; Galosy, S.; Koshida, S.; Niwa, S.; Bissell, M.J.

    1997-10-13

    Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.

  7. Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology

    PubMed Central

    Ferri, María José; Saez, Marc; Figueras, Joan; Fort, Esther; Sabat, Miriam; López-Ben, Santiago; de Llorens, Rafael; Aleixandre, Rosa Núria; Peracaula, Rosa

    2016-01-01

    Background There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19–9 (CA 19–9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. Methods CA 19–9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. Results The combination of CA 19–9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19–9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. Conclusions Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis. PMID:26808421

  8. Association of pancreatic adenocarcinoma up-regulated factor expression in ovarian mucinous adenocarcinoma with poor prognosis.

    PubMed

    Kim, Sang Kyum; Song, Si Young; Kim, Sunghoon; Cho, Nam Hoon; Yim, Ga Won; Kim, Sang Wun; Kim, Young Tae; Nam, Eun Ji

    2014-01-01

    Pancreatic adenocarcinoma up-regulated factor (PAUF) expression is elevated in both ovarian tumors and pancreatic adenocarcinoma. However, PAUF expression in ovarian tumors according to histologic subtype and grade has not been investigated. In this study, we examined various clinicopathologic features of 24 patients with mucinous cystadenoma (MCA), 36 with mucinous borderline tumors (MBTs), and 46 with mucinous adenocarcinomas (MACs) according to PAUF expression status assessed using immunohistochemistry. We found that MACs more frequently stained positive for PAUF than did MCAs and MBTs (P < 0.0001). Although there was no significant differences with respect to other clinicopathologic characteristics of MACs according to PAUF expression status, patients with PAUF-weakly positive and PAUF-strongly positive MACs tended to have a shorter overall survival (OS) than those with PAUF-negative MAC, determined using a Kaplan-Meier analysis (P = 0.1885). After adjusting for various clinicopathologic parameters, PAUF positivity of MACs was a significant predictive factor for disease-free survival (DFS) (negative vs. weakly positive: P = 0.045, hazard ratio [HR] = 57.406, 95% confidence interval [CI]: 1.090-3022.596; and negative vs. strongly positive: P = 0.034, HR = 97.890, 95% CI: 1.412-6785.925). In conclusion, PAUF was more frequently expressed in MAC than in its benign and borderline counterparts, and was associated with a poor OS and DFS in MAC patients. Therefore, we suggest that PAUF may be a practical biomarker for histopathological categorization and a prognostic marker for patients with an ovarian mucinous tumor. PMID:25197383

  9. Functional characterization of Mammary Gland Protein-40, a chitinase-like glycoprotein expressed during mammary gland apoptosis.

    PubMed

    Anand, Vijay; Jaswal, Shalini; Singh, Surender; Kumar, Sudarshan; Jena, Manoj Kumar; Verma, Arvind Kumar; Yadav, Munna Lal; Janjanam, Jagadeesh; Lotfan, Masoud; Malakar, Dhruba; Dang, Ajay Kumar; Mohanty, Tushar Kumar; Kaushik, Jai Kumar; Mohanty, Ashok Kumar

    2016-02-01

    MGP-40 is a chitinase-like protein which is over expressed during mammary gland involution. However, its physiological function in the mammary gland is poorly understood. In the present investigation, we have reported the functional significance of buffalo specific MGP-40 in the mammary gland by using an in vitro model of the buffalo mammary epithelial cell (BuMEC) line. MGP-40 was highly up regulated in BuMECs in serum starved condition as well as after treatment with prolactin suggesting its role in the stress response. Subsequently, to study the effect of MGP-40 on BuMECs, the cells were transfected with a mammalian expression construct of pCI neo harboring MGP-40 gene. It was observed that over expression of MGP-40 enhanced proliferation of BuMECs and protected the cells from apoptosis under serum free condition. In contrast, MGP-40 attenuated the mitogenic effect of insulin in BuMECs. Besides, over expression of the MGP-40 reduced dome formation, acinar polarization and casein synthesis in BuMECs in the presence of lactogenic hormones, it also induced Stat3 phosphorylation and epithelial to mesenchymal transition (EMT) -like features. Together, our data suggest that MGP-40 is involved in protection of BuMECs under stress conditions, inhibits cellular differentiation and induces EMT-like features. A schematic diagram depicting possible association of MGP-40 in various molecular pathways has been presented. PMID:26659075

  10. Enhanced mammary progesterone receptor-A isoform activity in the promotion of mammary tumor progression by dietary soy in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary contribution to breast cancer risk, recurrence, and progression remains incompletely understood. Increased consumption of soy and soy isoflavones is associated with reduced mammary cancer susceptibility in women and in rodent models of carcinogenesis. In rats treated with N-Methyl-N-Nitrosou...

  11. Regulation of adipocyte lipid homeostasis by genistein alters mammary epithelial cell differentiation: a paracrine mechanism for mammary tumor protection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological and animal studies have shown a negative correlation between breast cancer incidence and intake of soy rich foods. Our laboratory has studied soy protein isolate (SPI), the primary component of soy infant formula, as a paradigm to evaluate diet as a risk factor in mammary cancer. We ...

  12. Atlas of experimentally-induced neoplasia in beagle dogs

    SciTech Connect

    Dagle, G.E.; Watson, C.R.

    1996-10-01

    Beagle dogs have been utilized extensively in biomedical research. The US Department of Energy`s (DOE) Office of Health and Environmental Research (OHER) has sponsored life-span dose-effect radiation studies in beagles at various laboratories. Because results from studies in the various laboratories were to be compared, all the investigators strove to use similar nomenclature and criteria to describe biological effects. For this reason, pathologists from these laboratories met on five occasions between 1976 and 1977 to discuss nomenclature and histologic criteria for diagnoses. At these meeting, criteria were discussed for histopathologic description of lesions in bone, liver, lung, hematopoietic and lymphoid tissues, mammary gland, pituitary, testis, and thyroid. To provide further assurance of cooperation among the DOE laboratories involved, DOE organized several Task Groups in 1985, composed of staff members from the laboratories. The Task Group on Biological Effects was asked to standardize nomenclature and diagnostic criteria for pathology; this beagle pathology atlas is the result of that request. The atlas describes target organs of particular interest: lungs for radionuclides delivered by inhalation; bones for bone-seeking radionuclides; and hematopoietic and other soft tissues for external irradiation.

  13. Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway.

    PubMed

    Voutilainen, Maria; Lindfors, Päivi H; Trela, Ewelina; Lönnblad, Darielle; Shirokova, Vera; Elo, Teresa; Rysti, Elisa; Schmidt-Ullrich, Ruth; Schneider, Pascal; Mikkola, Marja L

    2015-11-01

    Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia on each flank of the embryo. It is thought that mammary cell fate can only be induced along the mammary line, a narrow region of the ventro-lateral skin running from the axilla to the groin. Ectodysplasin (Eda) is a tumor necrosis factor family ligand that regulates morphogenesis of several ectodermal appendages. We have previously shown that transgenic overexpression of Eda (K14-Eda mice) induces formation of supernumerary mammary placodes along the mammary line. Here, we investigate in more detail the role of Eda and its downstream mediator transcription factor NF-κB in mammary cell fate specification. We report that K14-Eda mice harbor accessory mammary glands also in the neck region indicating wider epidermal cell plasticity that previously appreciated. We show that even though NF-κB is not required for formation of endogenous mammary placodes, it is indispensable for the ability of Eda to induce supernumerary placodes. A genome-wide profiling of Eda-induced genes in mammary buds identified several Wnt pathway components as potential transcriptional targets of Eda. Using an ex vivo culture system, we show that suppression of canonical Wnt signalling leads to a dose-dependent inhibition of supernumerary placodes in K14-Eda tissue explants. PMID:26581094

  14. Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway

    PubMed Central

    Voutilainen, Maria; Lönnblad, Darielle; Shirokova, Vera; Elo, Teresa; Rysti, Elisa; Schmidt-Ullrich, Ruth; Schneider, Pascal; Mikkola, Marja L.

    2015-01-01

    Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia on each flank of the embryo. It is thought that mammary cell fate can only be induced along the mammary line, a narrow region of the ventro-lateral skin running from the axilla to the groin. Ectodysplasin (Eda) is a tumor necrosis factor family ligand that regulates morphogenesis of several ectodermal appendages. We have previously shown that transgenic overexpression of Eda (K14-Eda mice) induces formation of supernumerary mammary placodes along the mammary line. Here, we investigate in more detail the role of Eda and its downstream mediator transcription factor NF-κB in mammary cell fate specification. We report that K14-Eda mice harbor accessory mammary glands also in the neck region indicating wider epidermal cell plasticity that previously appreciated. We show that even though NF-κB is not required for formation of endogenous mammary placodes, it is indispensable for the ability of Eda to induce supernumerary placodes. A genome-wide profiling of Eda-induced genes in mammary buds identified several Wnt pathway components as potential transcriptional targets of Eda. Using an ex vivo culture system, we show that suppression of canonical Wnt signalling leads to a dose-dependent inhibition of supernumerary placodes in K14-Eda tissue explants. PMID:26581094

  15. Expression and Diagnostic Value of HE4 in Pancreatic Adenocarcinoma

    PubMed Central

    Huang, Tianhe; Jiang, Shi-Wen; Qin, Liangyi; Senkowski, Christopher; Lyle, Christian; Terry, Karen; Brower, Steven; Chen, Haibin; Glasgow, Wayne; Wei, Yongchang; Li, Jinping

    2015-01-01

    Human epididymis protein 4 (HE4) is a recognized biomarker in ovarian and endometrial cancer and over-expressed in pancreatic adenocarcinoma. The diagnostic value of HE4 in pancreatic adenocarcinoma remains unknown. Here we elucidate mRNA, protein and serum level of HE4 in pancreatic adenocarcinoma. HE4 mRNA level in tumor adjacent tissues and pancreatic adenocarcinoma tissues were tested by real time-PCR. Tissue microarray containing normal, adenocarcinoma, and adjacent pancreatic tissue was tested by immunohistochemistry (IHC). Serum level of HE4, carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3) and carbohydrate antigen 125 (CA125) were detected by ELISA assay in control and tumor patients. Further we compared the sensitivity and specificity of determining HE4, CA19-9, CA15-3, and CA125 for diagnosis of pancreatic adenocarcinoma and assessed the complementary diagnostic value of HE4, CA19-9, CA15-3 and CA125. Real time PCR showed significantly increased HE4 mRNA level in pancreatic adenocarcinoma compared with control. Result of IHC showed that HE4 significantly higher expressed in the human pancreatic carcinoma tissues than in both normal and adjacent non-tumorous pancreatic tissues, and the staining intensity is inversely correlated with the clinical stage. HE4 was highly expressed in early stage of pancreatic adenocarcinoma. Serum HE4 level is higher in cases with pancreatic adenocarcinoma than in the controls. Serum HE4 levels could research to a sensitivity of 45.83% and specificity of 93.75% when the Cutoff was set at 4.59 ng/mL. The Combined HE4 and CA19-9 increased the sensitivity to 83.33%; and interestingly, the combination of HE4 with CA15-3 led to the most powerful sensitivity of 87.5%. Combined with CA19-9 and CA15-3, HE4 could be a potential biomarker to improve the diagnostic power for pancreatic adenocarcinoma. PMID:25642754

  16. The Swiss Canine Cancer Registry: a retrospective study on the occurrence of tumours in dogs in Switzerland from 1955 to 2008.

    PubMed

    Grüntzig, K; Graf, R; Hässig, M; Welle, M; Meier, D; Lott, G; Erni, D; Schenker, N S; Guscetti, F; Boo, G; Axhausen, K; Fabrikant, S; Folkers, G; Pospischil, A

    2015-01-01

    Diagnostic records are a key feature of any cancer epidemiology, prevention or control strategy for man and animals. Therefore, the information stored in human and animal cancer registries is essential for undertaking comparative epidemiological, pathogenic and therapeutic research. This study presents the Swiss Canine Cancer Registry, containing case data compiled between 1955 and 2008. The data consist of pathology diagnostic records issued by three veterinary diagnostic laboratories in Switzerland. The tumours were classified according to the guidelines of the International Classification of Oncology for Humans on the basis of tumour type, malignancy and body location. The dogs were classified according to breed, age, sex, neuter status and place of residence. The diagnostic data were correlated with data on the Swiss general dog population and the incidence of cancer in dogs was thus investigated. A total of 67,943 tumours were diagnosed in 121,963 dogs and 47.07% of these were malignant. The most common tumour location was the skin (37.05%), followed by mammary glands (23.55%) and soft tissue (13.66%). The most common tumour diagnoses were epithelial (38.45%), mesenchymal (35.10%) and lymphoid tumours (13.23%). The results are compared with data in other canine registries and similarities in tumour distribution and incidence are noted. It is hoped that this study will mark the beginning of continuous registration of dog tumours in Switzerland, which, in turn, will serve as a reference for research in the fields of animal and human oncology. PMID:25824119

  17. Prevalence of Giardia and Cryptosporidium species in dog park attending dogs compared to non-dog park attending dogs in one region of Colorado.

    PubMed

    Wang, Andrea; Ruch-Gallie, Rebecca; Scorza, Valeria; Lin, Philip; Lappin, Michael R

    2012-03-23

    Dog parks are very popular in urban areas, but there are no current studies attempting to correlate visits to dog parks and risk of colonization by enteric parasites. The purpose of this study was to determine whether dog park visitation is associated with an increased prevalence of enteric parasites or an increase in prevalence of gastrointestinal signs in dogs in northern Colorado. Feces from dogs owned by veterinary students or Veterinary Teaching Hospital staff members were submitted with a completed survey form detailing dog park attendance rates, fecal character scores, and other clinical information. Feces were examined microscopically for parasites after sugar centrifugation, for Giardia spp. cysts and Cryptosporidium spp. oocysts by a commercially available immunofluorescence assay (FA) and the FA positive samples were genotyped after PCR amplification. The Giardia assemblages were determined using the glutamate dehydrogenase (GDH) β-giardin and triose phosphate isomerase (TPI) genes and the Cryptosporidium species were determined using the heat shock protein-70 gene. A total of 129 fecal samples were assayed; 66 were from dog park attending dogs and 63 were from non-dog park-attending dogs. The overall parasite prevalence rate was 7.0% (9 of 129 samples). Dog park attending dogs were more likely to be positive for Giardia or Cryptosporidium than non-dog park-attending dogs (p=0.0279), but there was no association of gastrointestinal signs with dog park attendance or with fecal flotation or FA results. The five Giardia isolates were assemblage C and/or D and the one Cryptosporidium isolate was Ctenocephalides canis. PMID:21890275

  18. Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast Agent in Companion Dogs with Naturally Occurring Cancer

    PubMed Central

    Ghaghada, Ketan B.; Sato, Amy F.; Starosolski, Zbigniew A.; Berg, John; Vail, David M.

    2016-01-01

    Objectives Companion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography (CT) imaging of solid tumors in companion dogs with naturally occurring cancer. Materials and Methods The institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years) with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study. Results Liposomal-I resulted in significant (p < 0.05) enhancement and uniform opacification of the vascular compartment. Non-renal, reticulo-endothelial systemic clearance of the contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan. Conclusions The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small

  19. Hyperoxic Treatment Induces Mesenchymal-to-Epithelial Transition in a Rat Adenocarcinoma Model

    PubMed Central

    Moen, Ingrid; Øyan, Anne Margrete; Kalland, Karl-Henning; Tronstad, Karl Johan; Akslen, Lars Andreas; Chekenya, Martha; Sakariassen, Per Øystein; Reed, Rolf Kåre; Stuhr, Linda Elin Birkhaug

    2009-01-01

    Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimetyl-α-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO2 = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO2 = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (∼16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the “switches” of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects. PMID:19636430

  20. Hyperoxic treatment induces mesenchymal-to-epithelial transition in a rat adenocarcinoma model.

    PubMed

    Moen, Ingrid; Øyan, Anne Margrete; Kalland, Karl-Henning; Tronstad, Karl Johan; Akslen, Lars Andreas; Chekenya, Martha; Sakariassen, Per Øystein; Reed, Rolf Kåre; Stuhr, Linda Elin Birkhaug

    2009-01-01

    Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimethyl-alpha-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO(2) = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO(2) = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (approximately 16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the "switches" of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects. PMID:19636430