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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. MAMMARY GLAND ADENOCARCINOMA IN A MALE BORNEAN ORANGUTAN (PONGO PYGMAEUS).

    PubMed

    Carpenter, Nancy A; Crook, Erika K

    2017-03-01

    An adult male Bornean orangutan ( Pongo pygmaeus ) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr postdetection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.

  3. Metastatic anaplastic adenocarcinoma suspected to be of mammary origin in an intact male rabbit (Oryctolagus cuniculus)

    PubMed Central

    Summa, Noémie M.; Eshar, David; Snyman, Heindrich N.; Lillie, Brandon N.

    2014-01-01

    A 7-year-old, intact male, pet dwarf rabbit (Oryctolagus cuniculus) was presented for a ventral abdominal subcutaneous mass. Histolopathology of the resected mass was suggestive of a mammary adenocarcinoma. Six months later, the rabbit died from severe dyspnea. Necropsy showed recurrence of the original mass with hepatic and pulmonary metastasis of the anaplastic adenocarcinoma, suspected to be of mammary origin. PMID:24790235

  4. Molecular Analysis of Motility in Metastatic Mammary Adenocarcinoma Cells

    DTIC Science & Technology

    1996-09-01

    Culture MTLn3 cells were clonally derived from a lung metastasis of the 13762NF rat mammary adenocarcinoma ( Neri et al., 1982) (kindly provided by Dr...MTLn3 cells were plated on collagen I coated MATTEK tissue culture dishes for 24 hours. Cells were plated at a density of 5000 cells/sq cm and...mM KOH; 4 mM MgC12 ; 10 mM EGTA pH 6.5 with 20 mM KOH; 5 1M phallacidin; 0.025 % saponin) was added to the culture well. After 15 seconds of extraction

  5. Malignant mammary tumor in female dogs: environmental contaminants.

    PubMed

    Andrade, Fábio He; Figueiroa, Fernanda C; Bersano, Paulo Ro; Bissacot, Denise Z; Rocha, Noeme S

    2010-06-30

    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.

  6. 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

  7. 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.

  8. Modulation of prostaglandin biosynthesis in murine mammary adenocarcinoma tumor cells

    SciTech Connect

    Shalinsky, D.R.

    1988-01-01

    In efforts to exploit the differential oxygen levels within the subcompartments of solid neoplasms, this project has focused on modulating prostaglandin (PG) biosynthesis under aerobic and hypoxic conditions. Mammary adenocarcinoma tumor cells (Line 4526), either intact or sonicated, were incubated with either 2.0 uM {sup 14}C-arachidonic acid (AA) or 20.0 uM {sup 14}C-PGH{sub 2}, respectively. Following metabolism, products were extracted, separated by thin layer chromatography and analyzed by radiochromatographic scan. PGE{sub 2} was predominantly formed with minimal amounts of PGF{sub 2a} or PGD{sub 2}. Indomethacin and ibuprofen inhibited the PGE{sub 2} formation from AA with an IC{sub 50} value of 6.3 {times} 10{sup {minus}8} and 9.6 {times} 10{sup {minus}5}M, respectively. Suspended cells in glass vials were made hypoxic by flushing with N{sub 2} for varying time intervals to study AA metabolism. A time-dependent inhibition of PG biosynthesis was observed under hypoxia, and by 30 min, the PGE{sub 2} synthesis was reduced by 50% which was further inhibited by indomethacin. Misonidazole, a 2-nitroimidazole analogue, partially reversed the inhibition of PGE{sub 2} synthesis under hypoxia by 49% at 100 uM. However, misonidazole did not affect PG biosynthesis under aerobic conditions. The stimulation of PGE{sub 2} biosynthesis by misonidazole under hypoxia was blocked by indomethacin, suggesting that misonidazole can not act independently of the cyclooxygenase.

  9. Aurora kinase-A overexpression in mouse mammary epithelium induces mammary adenocarcinomas harboring genetic alterations shared with human breast cancer.

    PubMed

    Treekitkarnmongkol, Warapen; Katayama, Hiroshi; Kai, Kazuharu; Sasai, Kaori; Jones, Jennifer Carter; Wang, Jing; Shen, Li; Sahin, Aysegul A; Gagea, Mihai; Ueno, Naoto T; Creighton, Chad J; Sen, Subrata

    2016-12-01

    Recent data from The Cancer Genome Atlas analysis have revealed that Aurora kinase A (AURKA) amplification and overexpression characterize a distinct subset of human tumors across multiple cancer types. Although elevated expression of AURKA has been shown to induce oncogenic phenotypes in cells in vitro, findings from transgenic mouse models of Aurora-A overexpression in mammary glands have been distinct depending on the models generated. In the present study, we report that prolonged overexpression of AURKA transgene in mammary epithelium driven by ovine β-lactoglobulin promoter, activated through multiple pregnancy and lactation cycles, results in the development of mammary adenocarcinomas with alterations in cancer-relevant genes and epithelial-to-mesenchymal transition. The tumor incidence was 38.9% (7/18) in Aurora-A transgenic mice at 16 months of age following 4-5 pregnancy cycles. Aurora-A overexpression in the tumor tissues accompanied activation of Akt, elevation of Cyclin D1, Tpx2 and Plk1 along with downregulation of ERα and p53 proteins, albeit at varying levels. Microarray comparative genomic hybridization (CGH) analyses of transgenic mouse mammary adenocarcinomas revealed copy gain of Glp1r and losses of Ercc5, Pten and Tcf7l2 loci. Review of human breast tumor transcriptomic data sets showed association of these genes at varying levels with Aurora-A gain of function alterations. Whole exome sequencing of the mouse tumors also identified gene mutations detected in Aurora-A overexpressing human breast cancers. Our findings demonstrate that prolonged overexpression of Aurora-A can be a driver somatic genetic event in mammary adenocarcinomas associated with deregulated tumor-relevant pathways in the Aurora-A subset of human breast cancer.

  10. 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.

  11. Cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a New Zealand white rabbit (Oryctolagus cuniculus).

    PubMed

    Sikoski, Paul; Trybus, James; Cline, J Mark; Muhammad, F Salih; Eckhoff, Andrew; Tan, Josh; Lockard, Mandy; Jolley, Tammy; Britt, Susan; Kock, Nancy D

    2008-06-01

    Pituitary adenoma in a rabbitA 44-mo-old, female, nulliparous New Zealand White Rabbit (Oryctolagus cuniculus) presented with bilaterally diffusely enlarged mammary glands with enlarged, discolored teats that exuded brown, mucoid discharge. The complete blood count and serum chemistry panels were within normal limits, bacteria were not isolated from a culture of the discharge, and the clinical signs did not resolve with antibiotic treatment. Computed tomography and serum prolactin levels supported the diagnosis of mammary gland dysplasia, possibly due to a prolactin-secreting pituitary adenoma. Histologic evaluation confirmed the presence of a pituitary adenoma, mammary hyperplasia, dysplasia, and cystic mammary adenocarcinoma. Immunohistochemical staining confirmed the presence of abundant prolactin secreting cells in the pituitary adenoma. This is the second report of hyperprolactinemia with mammary dysplasia in rabbits, and the first report of cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a rabbit.

  12. Cystic Mammary Adenocarcinoma Associated with a Prolactin-secreting Pituitary Adenoma in a New Zealand White Rabbit (Oryctolagus cuniculus)

    PubMed Central

    Sikoski, Paul; Trybus, James; Cline, J Mark; Muhammad, F Salih; Eckhoff, Andrew; Tan, Josh; Lockard, Mandy; Jolley, Tammy; Britt, Susan; Kock, Nancy D

    2008-01-01

    A 44-mo-old, female, nulliparous New Zealand White Rabbit (Oryctolagus cuniculus) presented with bilaterally diffusely enlarged mammary glands with enlarged, discolored teats that exuded brown, mucoid discharge. The complete blood count and serum chemistry panels were within normal limits, bacteria were not isolated from a culture of the discharge, and the clinical signs did not resolve with antibiotic treatment. Computed tomography and serum prolactin levels supported the diagnosis of mammary gland dysplasia, possibly due to a prolactin-secreting pituitary adenoma. Histologic evaluation confirmed the presence of a pituitary adenoma, mammary hyperplasia, dysplasia, and cystic mammary adenocarcinoma. Immunohistochemical staining confirmed the presence of abundant prolactin secreting cells in the pituitary adenoma. This is the second report of hyperprolactinemia with mammary dysplasia in rabbits, and the first report of cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a rabbit. PMID:18589874

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

    PubMed Central

    Burgess, Hilary J.; Wagner, Brent

    2016-01-01

    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

  14. Characterization of spheres derived from canine mammary gland adenocarcinoma cell lines.

    PubMed

    Michishita, Masaki; Akiyoshi, Rui; Yoshimura, Hisashi; Katsumoto, Takuo; Ichikawa, Hitoshi; Ohkusu-Tsukada, Kozo; Nakagawa, Takayuki; Sasaki, Nobuo; Takahashi, Kimimasa

    2011-10-01

    There is increasing evidence for the presence of cancer stem cells in several solid tumors, and these cancer stem cells have a potential role in tumor initiation, aggression, and recurrence. The stem cell-like properties of spheres derived from canine mammary tumors remain largely elusive. We attempted to induce sphere formation using four cell lines of canine mammary adenocarcinoma, and characterized the spheres derived from a CHMp line in vitro and in vivo. The CHMp-derived spheres showed predominantly CD44+CD24- population, higher expression of stem cell-related genes, such as CD133, Notch3 and MDR, and higher resistance to doxorubicin compared with the CHMp-derived adherent cells. Xenograft transplantations in nude mice demonstrated that only 1 × 10(4)sphere cells were sufficient for tumor formation. Use of the sphere assay on these sphere-derived tumors showed that sphere-forming cells were present in the tumors, and were maintained in serial transplantation. We propose that spheres derived from canine mammary adenocarcinoma cell lines possess a potential characteristic of cancer stem cells. Spheres derived from canine mammary tumors could be a powerful tool with which to investigate novel therapeutic drugs and to elucidate the molecular and cellular mechanisms that underlie tumorigenesis.

  15. Growth hormone mRNA in mammary gland tumors of dogs and cats.

    PubMed Central

    Mol, J A; van Garderen, E; Selman, P J; Wolfswinkel, J; Rijinberk, A; Rutteman, G R

    1995-01-01

    We have shown recently that in the dog progestin administration results in mammary production of immunoreactive growth hormone (GH). At present we demonstrate the expression of the gene encoding GH in the mammary gland of dogs and cats using reverse-transcriptase PCR. GH mRNA was found in the great majority of normal mammary tissues as well as benign and malignant mammary tumors of the dog and was associated with the presence of immunoreactive GH in cryostat sections. The mammary PCR product proved to be identical to that of the pituitary. The highest expression levels were found after prolonged treatment with progestins. In carcinomas GH mRNA was also found in progesterone receptor-negative tissue samples, indicating that after malignant transformation GH gene expression may become progestin independent. GH mRNA was also present in mammary tissues of cats with progestin-induced fibroadenomatous changes. It is concluded that GH gene expression occurs in normal, hyperplastic, and neoplastic mammary tissue of the dog. The expression in normal tissue is stimulated by progestins and might mediate the progestin-stimulated development of canine mammary tumors. The demonstration of progestin-stimulated GH expression in mammary tissue of cats indicates that the phenomenon is more generalized among mammals. Images PMID:7738169

  16. Stromal accumulation of chondroitin sulphate in mammary tumours of dogs

    PubMed Central

    Hinrichs, U; Rutteman, G R; Nederbragt, H

    1999-01-01

    To contribute to the investigation of the composition of the extracellular matrix in epithelial tumours, mammary gland tissues of dogs (including tumours, hyperplasias and normal tissue as well as metastatic lesions in lymph nodes and lung) were studied histochemically and immunohistochemically for distribution of sulphated glycosaminoglycans (s-GAGs). The formaline-fixed tissue was stained by alcian blue at pH 5.8, using the ‘critical electrolyte concentration’ to study the degree of sulphation of s-GAGs. s-GAGs were characterized by degradation with enzymes and nitrous acid and by immunohistochemistry with two anti-chondroitin sulphate monoclonal antibodies. The light microscopic investigation of s-GAG deposits revealed a limited number of patterns of their distribution. The main s-GAGs found in the mammary gland tumours of dogs and in metastatic lesions were chondroitin sulphate (CS) and heparin/heparan sulphate (HEP/HS). CS accumulated in diffuse structures between epithelial cells as well as around clusters of tumour cells. The latter pattern, possibly representing a mesenchymal reaction to the tumour, was present in 74% of the tumours, and in 67% of these, highly sulphated CS was present. A diffuse accumulation of CS was present almost exclusively in complex and mixed tumours; because of the expression of the 3B3 epitope for CS in immature cartilage the spindle cells of complex tumours are argued to be the precursors of the cartilage in mixed tumours. HEP/HS was stored mainly in mast cells that were found in increased numbers in hyperplasias and tumours. By pretreatment of microscopic slides with chondroitinase AC or ABC immunostaining of fibronectin could be made possible in areas in which CS was abundantly present, suggesting that CS may mask fibronectin epitopes. It is concluded that CS with different degrees of sulphation is the most important s-GAG in the extracellular matrix of mammary tumours of dogs. CS and other s-GAGs accumulate at different

  17. Detection of differentially expressed genes in methylnitrosourea-induced rat mammary adenocarcinomas.

    PubMed

    Hu, L; Lin, L; Crist, K A; Kelloff, G J; Steele, V E; Lubet, R A; You, M; Wang, Y

    1997-01-01

    In this study, altered gene expression in five methylnitrosourea (MNU)-induced rat mammary adenocarcinomas was investigated using a newly developed competitive cDNA library screening assay. In order to detect the differentially expressed cDNA transcripts, three cDNA libraries (rat mammary, rat liver, and rat kidney) with over 18,000 clones were differentially screened with competing normal and neoplastic mammary cDNA probes. Ninety-eight clones indicated by competitive hybridization to be differentially expressed in tumors were verified by dot-blot hybridization analysis. Of these clones, 45 were found to be overexpressed while 53 were underexpressed in tumors. Forty-five of the confirmed clones were further analyzed by single-pass cDNA sequence determination. Four clones showed homology with cytochrome oxidase subunit I, polyoma virus PTA noncoding region, cytoplasmic beta-actin, and mouse secretory protein containing thrombospondin motifs. Further investigation into the potential roles of these identified genes should contribute significantly to our understanding of the molecular mechanism(s) of rat mammary tumorigenesis.

  18. Genetic variations of BRCA1 and BRCA2 genes in dogs with mammary tumours.

    PubMed

    Enginler, S O; Akış, I; Toydemir, T S F; Oztabak, K; Haktanir, D; Gündüz, M C; Kırşan, I; Fırat, I

    2014-03-01

    Mammary tumours are the most common tumour type in female dogs. The formation of the mammary tumours is multifactorial but the high incidence of tumour disease in certain canine breeds suggests a strong genetic component. BRCA1 and BRCA2 are the most important genes significantly associated with mammary tumours. The aim of this study was to determine the association between the variations of these two genes and canine mammary tumours. 5'-untranslated region, intron 8 and exon 9 of BRCA1 and exons 12, 24, 27 of BRCA2 were sequenced in order to detect the genetic variations. In addition to six previously identified polymorphisms, six novel single nucleotide polymorphisms (SNPs) were detected. Five of the coding SNPs were synonymous and three of them were non-synonymous. The comparison of the sequences from 25 mammary tumour bearing and 10 tumour free dogs suggested that the two SNPs in intron 8 and exon 9 of BRCA1 and two SNPs in exon 24 and exon 27 of BRCA2, which are firstly identified in this study, might be associated with mammary tumour development in dogs. Especially one SNP in exon 9 of BRCA1 and one SNP in exon 24 of BRCA2 were found to be significantly associated with canine mammary tumours.

  19. Genetic variations of BRCA1 and BRCA2 genes in dogs with mammary tumours.

    PubMed

    Enginler, S O; Akış, I; Toydemir, T S F; Oztabak, K; Haktanir, D; Gündüz, M C; Kırşan, I; Fırat, I

    2014-03-01

    Mammary tumours are the most common tumour type in female dogs. The formation of the mammary tumours is multifactorial but the high incidence of tumour disease in certain canine breeds suggests a strong genetic component. BRCA1 and BRCA2 are the most important genes significantly associated with mammary tumours. The aim of this study was to determine the association between the variations of these two genes and canine mammary tumours. 5′-untranslated region, intron 8 and exon 9 of BRCA1 and exons 12, 24, 27 of BRCA2 were sequenced in order to detect the genetic variations. In addition to six previously identified polymorphisms, six novel single nucleotide polymorphisms (SNPs) were detected. Five of the coding SNPs were synonymous and three of them were non-synonymous. The comparison of the sequences from 25 mammary tumour bearing and 10 tumour free dogs suggested that the two SNPs in intron 8 and exon 9 of BRCA1 and two SNPs in exon 24 and exon 27 of BRCA2, which are firstly identified in this study, might be associated with mammary tumour development in dogs. Especially one SNP in exon 9 of BRCA1 and one SNP in exon 24 of BRCA2 were found to be significantly associated with canine mammary tumours.

  20. Platelet factors induce chemotactic migration of murine mammary adenocarcinoma cells with different metastatic capabilities.

    PubMed Central

    Sarach, M. A.; Rovasio, R. A.; Eynard, A. R.

    1993-01-01

    The chemotactic response of neoplastic cells (NC) induced by soluble platelet factors was investigated. NC suspensions isolated from murine mammary gland adenocarcinomas having different metastatic capabilities were incubated in Boyden's chambers and challenged with (1) 'Early Platelet Factors' (EP), obtained from the soluble fraction of recently collagen-activated human platelets, and (2) 'Late Platelet Factors' (LP), isolated after 24 hours incubation of the platelet aggregates. Chemotaxis was expressed as the distance travelled by NC through nitrocellulose filters. NC isolated from M3, the tumour line having the stronger metastatic potential, showed a significant chemotactic response towards LP factors, whereas NC from the M2 line exhibiting the lower metastatic behaviour, showed a chemotactic response towards EP factors. Both tumour cell lines lacked motion capability towards the well known chemoattractant peptide N-f-Met-Leu-Phe-Phe as well as to serum, plasma, collagen type I or culture medium. The different chemotactic response of both tumour lines when they were challenged by concentration gradients of factors released by early or late collagen-activated human platelets, confirm a relationship between platelet activity and metastatic capabilities and suggests that platelet chemoattractants might play a role in the metastatic dissemination of these mammary gland adenocarcinomas. Images Figure 1 PMID:8217786

  1. 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

  2. Clinical, cytologic, and histologic features of a mammary micropapillary carcinoma in a dog.

    PubMed

    Salgado, Breno S; Monteiro, Lidianne N; Colodel, Márcia M; Figueiroa, Fernanda C; Soares, Luisa M; Nonogaki, Suely; Rocha, Rafael M; Rocha, Noeme S

    2013-09-01

    Mammary invasive micropapillary carcinoma is a rare variant of mammary carcinoma that was recently recognized in dogs. The cytologic features and biologic behavior of such neoplasms in dogs have not yet been widely discussed in the veterinary literature. We report the clinical, cytologic, and histologic features of a canine micropapillary carcinoma in a 13-year-old female mongrel dog. The mammary region presented with extreme local pain, severe edema and erythema, and multifocal epidermal ulceration, which is typical for an inflammatory mammary carcinoma. Fine-needle aspirates were highly cellular and consisted of individual cells and papillary cell clusters with characteristics of malignant epithelial cells. Histologic examination revealed neoplastic cells arranged in small papillae without fibrovascular cores, sometimes inside clear lymphatic spaces, indicating lymphovascular invasion. Regional lymph node evaluation revealed metastatic cells. Due to deteriorating clinical condition the dog was euthanatized 5 months after mastectomy. At necropsy, metastatic neoplastic mammary cells were found in popliteal and mediastinal lymph nodes, the right femoral biceps muscle, liver, heart, lungs, and urinary bladder.

  3. Different muscarinc receptors are involved in the proliferation of murine mammary adenocarcinoma cell lines.

    PubMed

    Español, Alejandro J; Sales, María E

    2004-02-01

    We described that two different murine mammary adenocarcinoma cell lines, LM3 and LM2 constitutively expressed muscarinic acetylcholine receptors (mAchR). We here demonstrate, by competitive binding experiments with the tritiated muscarinic antagonist quinuclidinyl benzilate that M2 subtype predominates in both tumor cell lines. Concordantly immunoblotting assays indicate that mAchR exhibit the following order of expression: M2 > M4 > M3 > M1 > M5 in both tumor cell lines. Activation of mAchR with carbachol (CARB) increased proliferation in both tumor cell lines in a concentration dependent manner. In LM3 cells CARB promoted proliferation via M3 receptor activation via inositol 1,4,5-triphosphate and nitric oxide production. CARB-induced LM2 cells proliferation needed both M2 and M1 receptor activation, promoting prostaglandin E2 liberation and arginase catabolism respectively, both of them involved in tumor cell growth.

  4. Adenocarcinoma of mammary-like glands of the vulva: Report of a case and review of the literature.

    PubMed

    Abbott, Jared J; Ahmed, Iftikhar

    2006-04-01

    Mammary-like glands are a poorly recognized structure of normal vulvar skin. Adenocarcinomas arising from these glands are rare and represent a distinct clinicopathologic entity that must be distinguished from metastatic tumors. We reviewed 19 cases reported in the literature and describe a 51-year-old patient with a long-standing nodule on her right interlabial sulcus. Excisional biopsy and Mohs micrographic surgery demonstrated an infiltrating adenocarcinoma of the mammary-like glands involving the dermis and subcutis. On review of all 20 cases, the mean age at diagnosis was 59.6 years, the labia majora were involved in 13 cases (65%), and the mean lesional size was 2.5 cm. The tumor's histologic patterns varied greatly, although the histomorphologic similarity among this neoplasm, sweat gland carcinomas, and invasive extramammary Paget disease suggested a morphologic spectrum among these tumors. Criteria for establishing the diagnosis of adenocarcinoma of mammary-like glands include identifying transition zones between normal mammary-like glands and adenocarcinomatous areas. This tumor is best categorized as a locally aggressive neoplasm with a low risk for widespread metastasis. Use of aggressive surgical therapeutic regimens, particularly in the case of tumors localized to the skin, must be reassessed, especially given the likelihood of long-term morbidity with such regimens. In our patient, successful Mohs micrographic surgery suggests that alternate management may be adopted for tumors localized to the skin, especially in elderly patients.

  5. 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.

  6. 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.

  7. Immunohistochemical characterization of mammary squamous cell carcinoma of the dog.

    PubMed

    Sassi, Francesco; Sarli, Giuseppe; Brunetti, Barbara; Morandi, Federico; Benazzi, Cinzia

    2008-11-01

    Squamous cell carcinoma of the mammary gland is rare in both veterinary and human medicine. Whereas human metaplastic and squamous variants are known, the objectives of the current study were to ascertain the presence of such entities in canine mammary tumors and to distinguish them from other (epidermal, sweat gland) squamous tumors that may develop in the same area. A panel of antibodies (anti-cytokeratin [CK] 19, CK 14, CK 5/6, pancytokeratin, and vimentin) was used on 18 mammary gland malignancies with squamous features and 16 malignant skin tumors (11 squamous cell carcinomas of the skin and 5 sweat glands). Fifteen of the 18 mammary carcinomas were classified as metaplastic carcinomas, and the remaining 3 were classified as squamous cell carcinomas. The 2 most useful markers to establish the histogenesis of mammary tumors were pancytokeratin and CK 19. All other antibodies were equally expressed (CK 14 and 5/6) in all histotypes. The antibody panel discriminated primary epidermal squamous tumors (pancytokeratin positive and CK 19 negative) from gland-derived squamous neoplasms (pancytokeratin positive and CK 19 positive) but failed to distinguish primary mammary tumors from other squamous tumors of glandular origin.

  8. Inbreeding and canine mammary cancer: a retrospective study.

    PubMed

    Dorn, C R; Schneider, R

    1976-09-01

    Using files of the Animal Neoplasm Registry (ANR) in Alameda and Contra Costa Counties, California, we conducted a retrospective study to compare the degree of inbreeding in the ancestry of purebred dogs with mammary and other cancers, and of those without tumors. Wright's coefficients of inbreeding, calculated for all animals in the three groups, ranged from 0.000 to 0.535. The median inbreeding coefficients of the mammary cancer and comparison groups (consisting of other cancers) were approximately twice that of the nonneoplastic group, but neither difference was statistically significant. Dogs with mammary adenocarcinoma and mixed mammary cancer had similar degrees of inbreeding.

  9. A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs.

    PubMed

    Carvalho, Maria Isabel; Silva-Carvalho, Ricardo; Pires, Isabel; Prada, Justina; Bianchini, Rodolfo; Jensen-Jarolim, Erika; Queiroga, Felisbina L

    2016-01-01

    Infiltrating cells of the immune system are widely accepted to be generic constituents of tumor microenvironment. It has been well established that the development of mammary cancer, both in humans and in dogs, is associated with alterations in numbers and functions of immune cells at the sites of tumor progression. These tumor infiltrating immune cells seem to exhibit exclusive phenotypic and functional characteristics and mammary cancer cells can take advantage of signaling molecules released by them. Cancer related inflammation has an important role in mammary carcinogenesis, contributing to the acquisition of core hallmark capabilities that allow cancer cells to survive, proliferate, and disseminate. Indeed, recent studies in human breast cancer and in canine mammary tumors have identified a growing list of signaling molecules released by inflammatory cells that serve as effectors of their tumor-promoting actions. These include the COX-2, the tumor EGF, the angiogenic VEGF, other proangiogenic factors, and a large variety of chemokines and cytokines that amplify the inflammatory state. This review describes the intertwined signaling pathways shared by T-lymphocytic/macrophage infiltrates and important tissue biomarkers in both human and dog mammary carcinogenesis.

  10. A Comparative Approach of Tumor-Associated Inflammation in Mammary Cancer between Humans and Dogs

    PubMed Central

    Silva-Carvalho, Ricardo; Pires, Isabel; Bianchini, Rodolfo; Jensen-Jarolim, Erika

    2016-01-01

    Infiltrating cells of the immune system are widely accepted to be generic constituents of tumor microenvironment. It has been well established that the development of mammary cancer, both in humans and in dogs, is associated with alterations in numbers and functions of immune cells at the sites of tumor progression. These tumor infiltrating immune cells seem to exhibit exclusive phenotypic and functional characteristics and mammary cancer cells can take advantage of signaling molecules released by them. Cancer related inflammation has an important role in mammary carcinogenesis, contributing to the acquisition of core hallmark capabilities that allow cancer cells to survive, proliferate, and disseminate. Indeed, recent studies in human breast cancer and in canine mammary tumors have identified a growing list of signaling molecules released by inflammatory cells that serve as effectors of their tumor-promoting actions. These include the COX-2, the tumor EGF, the angiogenic VEGF, other proangiogenic factors, and a large variety of chemokines and cytokines that amplify the inflammatory state. This review describes the intertwined signaling pathways shared by T-lymphocytic/macrophage infiltrates and important tissue biomarkers in both human and dog mammary carcinogenesis. PMID:28053982

  11. Exposure to light-at-night increases the growth of DMBA-induced mammary adenocarcinomas in rats.

    PubMed

    Cos, Samuel; Mediavilla, Dolores; Martínez-Campa, Carlos; González, Alicia; Alonso-González, Carolina; Sánchez-Barceló, Emilio J

    2006-04-28

    In order to assess whether light exposure at night influences the growth of mammary tumors, as well as the role of melatonin in this process, female rats bearing DMBA-induced mammary adenocarcinomas were exposed to different lighting environments. Animals exposed to light-at-night, especially those under a constant dim light during the darkness phase, showed: (a) significantly higher rates of tumor growth as well as lower survival than controls, (b) higher concentration of serum estradiol, and (c) lower nocturnal excretion of 6-sulfatoxymelatonin, without there being differences between nocturnal and diurnal levels. These results suggest that circadian and endocrine disruption induced by light pollution, could induce the growth of mammary tumors.

  12. Primary clitoral adenocarcinoma with secondary hypercalcemia of malignancy in a dog.

    PubMed

    Neihaus, Steven A; Winter, Jennifer E; Goring, Robert L; Kennedy, F A; Kiupel, Matti

    2010-01-01

    This report describes a primary clitoral adenocarcinoma in a dog with secondary hypercalcemia of malignancy. A 10-year-old, spayed female basset hound was evaluated for a mass protruding from the vulva. The mass was excised, and a histological diagnosis of clitoral adenocarcinoma was made. No evidence of metastasis on thoracic radiographs or abdominal ultrasound was seen. Preoperative hypercalcemia resolved following excision of the mass. Cellular features were similar to an apocrine gland anal sac adenocarcinoma, and immunohistochemistry exhibited features noted with apocrine gland anal sac adenocarcinoma. No further treatment was elected by the owner. Internal iliac lymph-node metastasis was identified 4 weeks postoperatively, and hypercalcemia recurred 8 weeks postoperatively. The dog was euthanized 22 weeks postoperatively for signs related to hypercalcemia, including polyuria/polydipsia, lethargy, and weakness. A necropsy was performed and confirmed the presence of internal iliac lymph-node metastasis. The colon, rectum, and anal sacs were grossly and histologically normal. To our knowledge, this is the first reported case of clitoral neoplasia in the dog.

  13. [Ras gene analysis in mammary tumors of dogs by means of PCR-SSCP and direct genomic analysis].

    PubMed

    Castagnaro, M

    1995-01-01

    The oncogenic capacities of RAS family genes (Ha-ras, Ki-ras, and N-ras) are usually activated by point mutations in the conserved regions (codons 12, 13, and 61), resulting in single amino acid substitution in the specific proteins (p21). In order to verify the involvement of RAS genes in dog mammary tumors we analyzed the genomic DNA from 20 mammary tumors of dog by means of the Polymerase Chain Reaction-Single Strand Conformation Polymorphism (PCR-SSCP) method and the direct genomic sequencing. The absence of point mutations in the "hot spots" of RAS genes suggests a lack or a low frequency of such a pattern of RAS genes activation in dog mammary tumors. The results are also in agreement to what reported in human mammary tumors. However, the presence of genetic alterations in other functional areas of the RAS genes or other mechanisms of activations cannot be ruled out.

  14. 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.

  15. 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.

  16. 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.

  17. Muscarinic receptors participation in angiogenic response induced by macrophages from mammary adenocarcinoma-bearing mice

    PubMed Central

    de la Torre, Eulalia; Davel, Lilia; Jasnis, María A; Gotoh, Tomomi; de Lustig, Eugenia Sacerdote; Sales, María E

    2005-01-01

    Introduction The role of macrophages in tumor progression has generated contradictory evidence. We had previously demonstrated the ability of peritoneal macrophages from LMM3 murine mammary adenocarcinoma-bearing mice (TMps) to increase the angiogenicity of LMM3 tumor cells, mainly through polyamine synthesis. Here we investigate the ability of the parasympathetic nervous system to modulate angiogenesis induced by TMps through the activation of the muscarinic acetylcholine receptor (mAchR). Methods Peritoneal macrophages from female BALB/c mice bearing a 7-day LMM3 tumor were inoculated intradermally (3 × 105 cells per site) into syngeneic mice. Before inoculation, TMps were stimulated with the muscarinic agonist carbachol in the absence or presence of different muscarinic antagonists or enzyme inhibitors. Angiogenesis was evaluated by counting vessels per square millimeter of skin. The expression of mAchR, arginase and cyclo-oxygenase (COX) isoforms was analyzed by Western blotting. Arginase and COX activities were evaluated by urea and prostaglandin E2 (PGE2) production, respectively. Results TMps, which stimulate neovascularization, express functional mAchR, because carbachol-treated TMps potently increased new blood vessels formation. This response was completely blocked by preincubating TMps with pirenzepine and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), M1 and M3 receptor antagonists, and partly by the M2 receptor antagonist methoctramine. M1 receptor activation by carbachol in TMps triggers neovascularization through arginase products because Nω-hydroxy-L-arginine reversed the agonist action. Preincubation of TMps with methoctramine partly prevented carbachol-stimulated urea formation. In addition, COX-derived liberation of PGE2 is responsible for the promotion of TMps angiogenic activity by M3 receptor. We also detected a higher expression of vascular endothelial growth factor (VEGF) in TMps than in macrophages from normal mice. Carbachol

  18. 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.

  19. Influence of thorax irradiation on the survival of mice with spontaneous or artificial lung metastases from a transplantable mammary adenocarcinoma

    SciTech Connect

    Wondergem, J.; Haveman, J.; van der Schueren, E.

    1985-06-01

    The effect of thorax irradiation on lung metastases, either occurring spontaneously from a primary mammary adenocarcinoma (M8013X) transplanted on the leg or artificially induced by intravenous injection of tumor cells was studied. Increasing the interval between the moment at which lung metastases are supposed to originate and the thorax irradiation resulted in a rapid decrease of the effectiveness of this treatment in preventing the development of lung metastases. Increasing the radiation dose led to an increased number of cures; however, an increased number of mice dying of lethal lung damage was also observed. Irradiation of the lungs of mice with 5 or 10 Gy, 24 hours, 7 days or 14 days prior to i.v. injection with tumor cells, did not significantly increase the number of mice with lung metastases. Immunological resistance against the tumor played a role in our experiments with both spontaneous and artificial lung metastases.

  20. 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.

  1. 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

  2. Mammary tumors

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Mammary neoplasia is one of the more common malignancies affecting domestic species. Despite their importance, they are often over- diagnosed, undertreated and subject to several misconceptions propagated by veterinarians and pet owners alike. Mammary neoplasia is the most frequent tumor type encountered in the female accounting for almost half of all malignancies reported. The canine has the highest incidence of mammary tumors of all domestic species. In the dog, about 65 percent of mammary tumors are benign mixed tumors, and 25 percent are carcinomas. The rest are adenomas, myoepitheliomas, and malignant mixed tumors. The age distribution of mammary tumors closely follows the age distribution of most tumors in the dog. Mammary tumors are rare in dogs 2 years old, but incidence begins to increase sharply at approximately 6 years of age. Median age at diagnosis is about 10 years. No breed predilection has been consistently reported.

  3. Serum Galectin-3 Levels in Dogs with Metastatic and Non-metastatic Mammary Tumors.

    PubMed

    Ribeiro, Cláudia; Santos, Mariana Sá; DE Matos, Augusto J; Barros, Rita; Gärtner, Fátima; Rutteman, Gerard R; DE Oliveira, Joana T

    2016-01-01

    Galectin-3 is implicated in tumor progression and metastasis. High levels of galectin-3 have been reported in intravasated cells in primary and metastatic tumor sites of canine malignant mammary tumors (CMMT). Nevertheless, it is still unknown whether this increase is limited to the site of the lesion or if it is a systemic feature. To better understand the pattern of the expression of galectin-3 and to investigate the possibility of using serum galectin-3 levels as a relevant biomarker in this disease, galectin-3 concentrations were determined in a series of sera from CMMT-bearing female dogs. None of the dogs included in the study had detectable metastases at the time of presentation. Animals were retrospectively divided into two groups dependent on whether or not they developed metastatic lesions during a 25-month follow-up period. Samples were collected from all dogs before surgery, 1 month after resection of the primary tumor and every 3 months during the postoperative period. Galectin-3 levels were significantly higher 1 month after than at the time of surgery (p=0.0058). Higher galectin-3 was found in samples collected 7 (p=0.0007), 10 (p=0.0061) and 13 months (p=0.0052) after surgery from dogs of the metastatic group when compared to those remaining free of development of detectable metastases. In conclusion, increased serum galectin-3 levels seem to be present in both metastatic and non-metastatic cases during the postoperative period, however, while in non-metastatic cases the values tend to return to baseline levels after surgery, in metastatic cases, levels remain persistently elevated.

  4. Giant cells in anaplastic mammary carcinoma of the dog and cat.

    PubMed

    Della Salda, L; Sarli, G; Benazzi, C; Marcato, P S

    1993-11-01

    Four uncommon anaplastic mammary carcinomas containing numerous giant cells are described in three dogs and one cat. The giant cells of all cases were studied by means of monoclonal and polyclonal antibodies to detect epithelial (carcinoembryonic antigen and keratin) and mesenchymal (vimentin, lysozyme and S-100 protein) differentiation. Most of them proved to have an epithelial immunophenotype. Ultrastructurally, scattered bundles of tonofilaments but no lysosome-like bodies could be detected. One tumour had an additional, different type of giant cell, which had a benign multinucleated osteoclast-like appearance, gave positive staining for acid phosphatase, had a histiocytic-stromal immunohistochemical pattern, and was, ultrastructurally, multinucleate with irregular folds and no evidence of tonofilaments. In one case some giant cells had an epithelial immunophenotype and others a stromal immunophenotype, even though their histological and ultrastructural features were the same. In the least histologically differentiated tumour the giant cells presented a coexpression of intermediate filaments. This supported the theory that there might be a stem cell origin for most canine mammary tumours.

  5. Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index

    PubMed Central

    Bedin, Chiara; Romualdi, Chiara; Mainenti, Marta; Mollo, Antonio; Cavicchioli, Laura; Ferro, Silvia; Trez, Davide; De Maria, Raffaella; Nitti, Donato; Saccani, Andrea; Campanella, Michelangelo; Agostini, Marco; Zappulli, Valentina

    2017-01-01

    Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs. The cfDNA fragments and integrity index significantly differentiated neoplastic versus non-neoplastic dogs (P<0.05), and allowed the distinction between benign and malignant lesions (P<0.05). Even if without statistical significance, the amount of cfDNA was also affected by tumor necrosis and correlated with tumor size and apoptotic markers expression. A significant (P<0.01) increase of Bcl-2 in malignant tumors was observed, and in metastatic CMTs the evasion of apoptosis was also suggested. This study, therefore, provides evidence that cfDNA could be a diagnostic marker in dogs carrying mammary nodules suggesting that its potential application in early diagnostic procedures should be further investigated. PMID:28081183

  6. Evaluation of adjuvant carboplatin chemotherapy in the management of surgically excised anal sac apocrine gland adenocarcinoma in dogs.

    PubMed

    Wouda, R M; Borrego, J; Keuler, N S; Stein, T

    2016-03-01

    There is no widely accepted standard of care for canine anal sac apocrine gland adenocarcinoma (ASAGAC). Surgery alone is inadequate in many cases, but the benefit of adjuvant chemotherapy is not well established. The primary objective of this retrospective study was to evaluate the role of carboplatin chemotherapy in the post-operative management of ASAGAC. Seventy-four dogs with naturally occurring ASAGAC underwent surgery. Forty-four dogs received adjuvant carboplatin and 30 did not. Median overall survival (OS) was 703 days. Median time to progression (TTP) was 384 days. Only primary tumour size and lymph node metastasis at diagnosis significantly impacted the outcome. Differences in OS and TTP, between the dogs that received adjuvant carboplatin and those that did not, failed to reach statistical significance. Treatment of progressive disease, whilst not limited to chemotherapy, significantly prolonged the survival. This study shows that adjuvant carboplatin chemotherapy is well tolerated and may have a role in the management of dogs with ASAGAC.

  7. Stabilin-1 is expressed in human breast cancer and supports tumor growth in mammary adenocarcinoma mouse model

    PubMed Central

    Riabov, Vladimir; Yin, Shuiping; Song, Bin; Avdic, Aida; Schledzewski, Kai; Ovsiy, Ilja; Gratchev, Alexei; Verdiell, Maria Llopis; Sticht, Carsten; Schmuttermaier, Christina; Schönhaber, Hiltrud; Weiss, Christel; Fields, Alan P.; Simon-Keller, Katja; Pfister, Frederick; Berlit, Sebastian; Marx, Alexander; Arnold, Bernd; Goerdt, Sergij; Kzhyshkowska, Julia

    2016-01-01

    Stabilin-1 is a multifunctional scavenger receptor expressed on alternatively-activated macrophages. Stabilin-1 mediates phagocytosis of “unwanted-self” components, intracellular sorting, and endocytic clearance of extracellular ligands including SPARC that modulates breast cancer growth. The expression of stabilin-1 was found on tumor-associated macrophages (TAM) in mouse and human cancers including melanoma, lymphoma, glioblastoma, and pancreatic insulinoma. Despite its tumor-promoting role in mouse models of melanoma and lymphoma the expression and functional role of stabilin-1 in breast cancer was unknown. Here, we demonstrate that stabilin-1 is expressed on TAM in human breast cancer, and its expression is most pronounced on stage I disease. Using stabilin-1 knockout (ko) mice we show that stabilin-1 facilitates growth of mouse TS/A mammary adenocarcinoma. Endocytosis assay on stabilin-1 ko TAM demonstrated impaired clearance of stabilin-1 ligands including SPARC that was capable of inducing cell death in TS/A cells. Affymetrix microarray analysis on purified TAM and reporter assays in stabilin-1 expressing cell lines demonstrated no influence of stabilin-1 expression on intracellular signalling. Our results suggest stabilin-1 mediated silent clearance of extracellular tumor growth-inhibiting factors (e.g. SPARC) as a mechanism of stabilin-1 induced tumor growth. Silent clearance function of stabilin-1 makes it an attractive candidate for delivery of immunomodulatory anti-cancer therapeutic drugs to TAM. PMID:27105498

  8. 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.

  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. 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.

  11. Differential effects of dietary Oenothera, Zizyphus mistol, and corn oils, and essential fatty acid deficiency on the progression of a murine mammary gland adenocarcinoma.

    PubMed

    Muñoz, S E; Piegari, M; Guzmán, C A; Eynard, A R

    1999-03-01

    The modulating effect of dietary enrichment in mistol seed oil (MO) containing 25% of alpha-linolenic acid (ALA), evening primrose oil (EPO) enriched in gamma-linolenic acid (GLA) and corn oil (CO) as sources of omega-6 and omega-9 fatty acids on the growth parameters of one transplantable mammary tumor were compared. Mice fed on different lipid formulae were inoculated with a mammary gland adenocarcinoma and different growth development tumor parameters were recorded. Results showed that corn oil feeding slowed down most of the tumor growth parameters, as did the EPO diet. MO also showed antitumor activity. Olein feeding, which induces an essential fatty acid deficiency (EFAD), increased the incidence and the multiplicity of metastases when compared with the controls. It may be concluded that a diet enriched in omega-6 fatty acids did not behave as a tumor promoter in this mammary gland tumor model. The antitumor activities of EPO and MO are corroborated in present experiments, suggesting that both oils may be of value in nutritional approaches of mammary gland tumor therapies. In addition, present data add further experimental proof about the proposed protumorigenic proneness induced by the EFAD state.

  12. High and low dose radiation effects on mammary adenocarcinoma cells - an epigenetic connection.

    PubMed

    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.

  13. 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

  14. 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.

  15. Salivary gland tumor "wishes" to add to the next WHO Tumor Classification: sclerosing polycystic adenosis, mammary analogue secretory carcinoma, cribriform adenocarcinoma of the tongue and other sites, and mucinous variant of myoepithelioma.

    PubMed

    Gnepp, Douglas R

    2014-03-01

    This review is a continuation of suggested tumor additions to the next WHO Tumor Classification. The author will focus on four salivary gland entities that have recently become accepted in the literature as new neoplastic entities: sclerosing polycystic adenosis, mammary analogue secretory carcinoma, cribriform adenocarcinoma of the tongue and other sites, and mucinous variant of myoepithelioma.

  16. A New Hitherto Unreported Histopathologic Manifestation of Mammary Analogue Secretory Carcinoma: "Masked MASC" Associated With Low-grade Mucinous Adenocarcinoma and Low-grade In Situ Carcinoma Components.

    PubMed

    Petersson, Fredrik; Michal, Michael; Kazakov, Dmitry V; Grossmann, Petr; Michal, Michal

    2016-10-01

    We present a salivary gland tumor of the parotid gland in a 54-year-old woman, which contained a minor mammary analogue secretory carcinoma (MASC) component (20%) intermixed with a morphologically entirely different mucinous adenocarcinomatous component that comprised 80% of the tumor mass and a morphologically nondescript low-grade intraductal carcinoma (in situ) component. On fluorescence in situ hybridization, a break in the ETV6 gene was documented in the mucinous adenocarcinomatous, the conventional MASC, and the intraductal (in situ) components. RT-PCR failed to reveal an ETV6-NTRK3 fusion. The entire conventional MASC and only rare mucinous adenocarcinoma tumor cells were mammaglobin positive, whereas the low-grade intraductal carcinoma (in-situ) component was negative. S-100 protein stained only the MASC component.

  17. Deoxyelephantopin impedes mammary adenocarcinoma cell motility by inhibiting calpain-mediated adhesion dynamics and inducing reactive oxygen species and aggresome formation.

    PubMed

    Lee, Wai-Leng; Shyur, Lie-Fen

    2012-04-15

    We previously showed that deoxyelephantopin (DET), a plant sesquiterpene lactone, exhibits more profound suppression than paclitaxel (PTX) of lung metastasis of mammary adenocarcinoma TS/A cells in mice. Proteomics studies suggest that DET affects actin cytoskeletal protein networks and downregulates calpain-mediated proteolysis of several actin-associated proteins, whereas PTX mainly interferes with microtubule proteins. Here, DET was observed to significantly deregulate adhesion formation in TS/A cells, probably through inhibition of m-calpain activity. Epithelial growth factor (EGF)-mediated activation of Rho GTPase Rac1 and formation of lamellipodia in TS/A cells were remarkably suppressed by DET treatment. Further, DET impaired vesicular trafficking of EGF and induced protein carbonylation and formation of centrosomal aggregates in TS/A cells. DET-induced reactive oxygen species were observed to be the upstream stimulus for the formation of centrosomal ubiquitinated protein aggregates that might subsequently restrict cancer cell motility. PTX, however, caused dramatic morphological changes, interfered with microtubule networking, and moderately inhibited calpain-mediated cytoskeletal and focal adhesion protein cleavage in TS/A cells. This study provides novel mechanistic insights into the pharmacological action of DET against metastatic mammary cell migration and suggests that modulation of oxidative stress might be a potential strategy for treatment of metastatic breast cancer.

  18. Effect of ω-3 and ω-9 fatty acid rich oils on lipoxygenases and cyclooxygenases enzymes and on the growth of a mammary adenocarcinoma model

    PubMed Central

    2010-01-01

    Background Nutritional factors play a major role in cancer initiation and development. Dietary polyunsaturated fatty acids (PUFAs) have the ability to induce modifications in the activity of lipoxygenase (LOX) and cyclooxygenase (COX) enzymes that affect tumour growth. We studied the effect of two diets enriched in 6% Walnut and Peanut oils that are rich in ω-3 and ω9 PUFAs respectively on a murine mammary gland adenocarcinoma as compared with the control (C) that received commercial diet. Results Peanut oil enriched diet induced an increase in membrane arachidonic acid (AA) content and the cyclooxygenase enzyme derived 12-HHT (p < 0.05) and simultaneously showed decrease in 12-LOX, 15-LOX-2, 15-LOX-1 and PGE activities (p < 0.05) that corresponded to higher apoptosis and lower mitosis seen in this group (p < 0.05). Furthermore, Peanut oil group showed lower T-cell infiltration (p < 0.05), number of metastasis (p < 0.05) and tumour volume (p < 0.05) and longer survival rate compared to other groups. Conclusions The results of the present study showed that Peanut oil-enriched diet protects against mammary cancer development by modulating tumour membrane fatty acids composition and LOX and COX enzyme activities. PMID:20932327

  19. In vivo 31P NMR Study of the Metabolism of Murine Mammary 16/C Adenocarcinoma and Its Response to Chemotherapy, X-Radiation, and Hyperthermia

    NASA Astrophysics Data System (ADS)

    Evanochko, W. T.; Ng, T. C.; Lilly, M. B.; Lawson, A. J.; Corbett, T. H.; Durant, J. R.; Glickson, J. D.

    1983-01-01

    31P NMR spectroscopy with surface coils has been used to monitor, in vivo, the phosphate metabolism of subcutaneously implanted mammary 16/C adenocarcinoma in C3H/He mice. This model tumor was studied during untreated tumor growth and after treatment with adriamycin, hyperthermia, and x-radiation. The mammary 16/C tumor exhibited a Gompertzian growth pattern. Levels of high-energy phosphate metabolites--phosphocreatine and ATP--decreased with increases in tumor mass. There was a concomitant increase in the level of Pi and a decrease in the apparent pH of the tumor. These spectral changes appear to reflect changes in tumor vascularization that accompany tumor growth, the tumor becoming progressively more hypoxic. Partial response of this tumor to chemotherapy with adriamycin was reflected in a small but measurable increase in the phosphocreatine resonance, a decrease in Pi, and a return of the intratumor pH to neutral. Hyperthermia resulted in progressive conversion of the 31P NMR spectrum to that of a dead tumor (high levels of Pi, small levels of residual sugar phosphates and pyridine dinucleotides, and acidic pH). X-irradiation (14.0 Gy) led to disappearance of the phosphocreatine peak within 15 min of treatment. Subsequently, this resonance grew back beyond its pretreatment level. As the tumor receded, its spectrum reflected the characteristics of aerobically metabolizing tissue (high levels of phosphocreatine and ATP and low levels of Pi and sugar phosphates).

  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. Mast cells in canine cutaneous hemangioma, hemangiosarcoma and mammary tumors.

    PubMed

    Woldemeskel, Moges; Rajeev, Sreekumari

    2010-02-01

    Mast cell count (MCC) in 45 dogs with cutaneous hemangioma (HA, n = 12), hemangiosarcoma (HSA, n = 12), mammary adenoma (AD, n = 9) and mammary adenocarcinoma (AC, n = 12) was made using Toluidine blue stained sections. Antibodies against endothelial cell markers, Factor VIII and VEGF were used to visualize and determine the hot spot micro-vessel density (MVD). Total MCC and MCC along the invasive edges were significantly higher (p < 0.001) in canine mammary AC than in AD. The total MCC did not significantly differ (p > 0.05), in HSAs (8.6 +/- 3.3) than in HAs (5.5 +/- 2.8). There is a positive correlation (r = 0.14) between the hot spot MCC and MVD in mammary AC, although not significant (p = 0.3172), indicating that mast cells are associated with angiogenesis in canine mammary AC. This study suggests that mast cells may play an important role in neovascularization of canine cutaneous vascular and mammary neoplasms. Detailed studies encompassing correlation of MCC and MVD with clinical outcomes and prognosis in these neoplasms are recommended.

  2. Morphological Aspects and Immunophenotypic Profiles of Mammary Carcinomas in Benign-Mixed Tumors of Female Dogs

    PubMed Central

    Ribeiro, Gustavo Meirelles; Bertagnolli, Angélica Cavalheiro; Rocha, Rafael Malagoli; Cassali, Geovanni Dantas

    2012-01-01

    Carcinoma in benign-mixed tumor (CBMT) is common in the female canine mammary gland and comprises malignant epithelial between benign mesenchymal elements. This study investigated the morphological aspects of 29 CBMT and their immunophenotypical profiles, by using an immunohistochemistry panel based on five molecular markers—estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5 (CK5), and human epidermal growth factor receptor 1 (EGFR). From these, CBMT was classified into four subtypes: luminal A, luminal B, HER2-like, basal-like, and normal. “In situ” and invasive carcinomatous components were analyzed and compared. Histological grade I carcinoma was observed in 16 cases (55.2%) of the tumors analyzed, grade II in 10 cases (34.5%), and grade III in three cases (10.3%). The invasive carcinomatous component has shown, more frequently, luminal A (12/29 cases, 41.4%), followed by basal-like phenotype (8/29 cases, 27.6%). There was high concordance between immunophenotypical profiles of the in situ and invasive carcinomatous components (kappa coefficient = 0.816, P < 0.001). We concluded that CBMT predominantly has features of low-grade neoplasms of malignancy. The various immunophenotypic profiles suggest the origin of these lesions in more than one cell type (luminal and myoepithelial). PMID:23029631

  3. Highly metastatic 13762NF rat mammary adenocarcinoma cell clones stimulate bone marrow by secretion of granulocyte-macrophage colony-stimulating factor/interleukin-3 activity.

    PubMed

    McGary, C T; Miele, M E; Welch, D R

    1995-12-01

    Circulating neutrophil (polymorphonuclear leukocyte levels rise 50-fold in 13762NF tumor-bearing rats in proportion to the tumor's metastatic potential. Purified tumor-elicited neutrophils enhance metastasis of syngeneic tumor cells when co-injected intravenously; however, circulating and phorbol ester-activated polymorphonuclear neutrophils do not. The purpose of this study was to elucidate the source of tumor-elicited neutrophils in metastatic tumor-bearing rats. We examined the bone marrow in rats bearing tumors of poorly, moderately, and highly metastatic cell clones. Marrow from rats with highly metastatic tumors had increased cellularity (100%), myeloid to erythroid ratio (10:1), and megakaryocytes compared with control rats (cellularity, approximately 80%; myeloid to erythroid ratio, 5:1), with marrows from rats with moderately metastatic tumors having intermediate values. This suggested production of a colony-stimulating factor by the metastatic cells. To confirm this, bone marrow colony formation from control and tumor-bearing rats was compared. Colony number increased in proportion to the metastatic potential of the tumor. Conditioned medium from metastatic cells supported growth of the granulocyte-macrophage colony-stimulating factor/interleukin-3-dependent 32Dcl3 cell line, but media from nonmetastatic or moderately metastatic cells did not. Antibodies to murine granulocyte-macrophage colony-stimulating factor neutralized 32Dcl3 growth in tumor cell conditioned medium. These results suggest production of a granulocyte-macrophage colony-stimulating factor or interleukin-3-like activity by highly metastatic 13762NF clones and implicate a possible role for colony-stimulating factors in regulating the metastatic potential of mammary adenocarcinoma cell clones.

  4. 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

  5. Three-dimensional conformal versus non-graphic radiation treatment planning for apocrine gland adenocarcinoma of the anal sac in 18 dogs (2002-2007).

    PubMed

    Keyerleber, M A; Gieger, T L; Erb, H N; Thompson, M S; McEntee, M C

    2012-12-01

    Differences in dose homogeneity and irradiated volumes of target and surrounding normal tissues between 3D conformal radiation treatment planning and simulated non-graphic manual treatment planning were evaluated in 18 dogs with apocrine gland adenocarcinoma of the anal sac. Overall, 3D conformal treatment planning resulted in more homogenous dose distribution to target tissues with lower hot spots and dose ranges. Dose homogeneity and guarantee of not under-dosing target tissues with 3D conformal planning came at the cost, however, of delivering greater mean doses of radiation and of irradiating greater volumes of surrounding normal tissue structures.

  6. Feline mammary basal-like adenocarcinomas: a potential model for human triple-negative breast cancer (TNBC) with basal-like subtype

    PubMed Central

    2013-01-01

    Background Breast cancer is one of the leading causes of cancer deaths. Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer susceptibility) mutations. Feline mammary adenocarcinomas (FMAs) are highly malignant and share a similar basal-like subtype. The purpose of this study was to classify FMAs according to the current human classification of breast cancer that includes evaluation of ER, PR and HER2 status and expression of basal CK 5/6 and EGFR. Furthermore, we selected triple negative, basal-like FMAs to screen for BRCA mutations similar to those described in human TNBC. Methods Twenty four FMAs were classified according to the current human histologic breast cancer classification including immunohistochemistry (IHC) for ER, PR HER2, CK5/6 and EGFR. Genetic alteration and loss of heterozygosity of BRCA1 and BRCA2 genes were analyzed in triple negative, basal-like FMAs. Results IHC for ER, PR and HER2 identified 14 of the 24 (58%) FMAs as a triple negative. Furthermore, 11of these 14 (79%) triple negative FMAs had a basal-like subtype. However, no genetic abnormalities were detected in BRCA1 and BRCA2 by direct sequencing and loss of heterozygosity analysis. Conclusion FMAs are highly aggressive neoplasms that are commonly triple negative and exhibit a basal-like morphology. This is similar to human TNBC that are also commonly classified as a basal-like subtype. While sequencing of a select number of triple negative, basal-like FMAs and testing for loss of heterozygosity of BRCA1 and BRCA2 did not identify mutations similar to those described in human TNBC, further in-depth evaluation is required

  7. The dog as a natural animal model for study of the mammary myoepithelial basal cell lineage and its role in mammary carcinogenesis.

    PubMed

    Rasotto, R; Goldschmidt, M H; Castagnaro, M; Carnier, P; Caliari, D; Zappulli, V

    2014-01-01

    Basal-like tumours constitute 2-18% of all human breast cancers (HBCs). These tumours have a basal myoepithelial phenotype and it has been hypothesized that they originate from either myoepithelial cells or mammary progenitor cells. They are heterogeneous in morphology, clinical presentation, outcome and response to therapy. Canine mammary carcinomas (CMCs) have epidemiological and biological similarities to HBCs, are frequently biphasic and are composed of two distinct neoplastic populations (epithelial and myoepithelial). The present study evaluates the potential of CMCs as a natural model for basal-like HBCs. Single and double immunohistochemistry was performed on serial sections of 10 normal canine mammary glands and 65 CMCs to evaluate expression of cytokeratin (CK) 8/18, CK5, CK14, α-smooth muscle actin (SMA), calponin (CALP), p63 and vimentin (VIM). The tumours were also evaluated for Ki67 and human epidermal growth factor receptor (HER)-2 expression. A hierarchical model of cell differentiation was established, similar to that for the human breast. We hypothesized that progenitor cells (CK5(+), CK14(+), p63(+) and VIM(+)) differentiate into terminally-differentiated luminal glandular (CK8/18(+)) and myoepithelial (CALP(+), SMA(+) and VIM(+)) cells via intermediary luminal glandular cells (CK5(+), CK14(+) and CK8/CK18(+)) and intermediary myoepithelial cells (CK5(+), CK14(+), p63(+), SMA(+), CALP(+) and VIM(+)). Neoplastic myoepithelial cells in canine complex carcinomas had labelling similar to that of terminally-differentiated myoepithelial cells, while those of carcinomas-and-malignant myoepitheliomas with a more aggressive biological behaviour (i.e. higher frequency of vascular/lymph node invasion and visceral metastases and higher risk of tumour-related death) were comparable with intermediary myoepithelial cells and had significantly higher Ki67 expression. The majority of CMCs examined were negative for expression of HER-2. The biphasic appearance of

  8. Allelotyping of butadiene-induced lung and mammary adenocarcinomas of B6C3F1 mice: frequent losses of heterozygosity in regions homologous to human tumor-suppressor genes.

    PubMed Central

    Wiseman, R W; Cochran, C; Dietrich, W; Lander, E S; Söderkvist, P

    1994-01-01

    To identify the potential involvement of tumor-suppressor gene inactivation during neoplastic development in B6C3F1 mice, genetic losses were determined from allelotypes of butadiene-induced lung and mammary adenocarcinomas. By using length polymorphisms in restriction fragments and simple sequence repeats, or "microsatellites," markers on each autosome were analyzed for allele losses in tumor DNAs. Losses of heterozygosity on chromosome 11 were observed at several loci surrounding the p53 tumor-suppressor gene (Trp53) in 12 of 17 mammary tumors and 2 of 8 lung tumors. Although most of these alterations appeared to result from nondisjunction, at least two examples of somatic recombination or deletion were also observed. Southern analysis revealed a homozygous deletion of the remaining Trp53 allele of one of these mammary tumors. Losses of heterozygosity were also detected at the Rb-1 tumor-suppressor gene in 7 of 17 mammary tumors and 1 lung tumor. Finally, frequent allele losses were observed on chromosome 4 in lung tumors. Analysis of nine chromosome 4 loci defined an interstitial deletion containing the Ifa gene cluster in one of the lung tumors. A tumor-suppressor gene was previously mapped to this region of chromosome 4 in studies with somatic cell hybrids. In addition, homozygous deletions have been reported in a homologous region of human chromosome 9p for acute lymphocytic leukemias, glioblastomas, melanomas, and lung carcinomas. These findings suggest that the inactivation of tumor-suppressor genes including Trp53, Rb-1, and an unidentified gene on chromosome 4 plays a significant role during carcinogenesis in mice. Images PMID:8170984

  9. Dogs

    MedlinePlus

    ... Healthy People Health Benefits of Pets Pets Birds Cats Dogs Farm Animals Backyard Poultry Ferrets Fish Horses ... Sharks Help Wounded Warriors Heal Loving Your Special Cat Parrots Make Friends for Life Tracking the Mysterious ...

  10. 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

  11. 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.

  12. Canine mammary gland tumors.

    PubMed

    Sorenmo, Karin

    2003-05-01

    The National Consensus Group recommends that all women with tumors larger than 1 cm be offered chemotherapy regardless of tumor histology of lymph node status. This recommendation is to ensure that everyone at risk for failing, even though the risk may be low in women with relatively small tumors and favorable histology, has a choice and receives the benefit of adjuvant chemotherapy. This type of treatment recommendation may also be made in dogs based on recognized, well-accepted prognostic factors such as tumor size, stage, type, and histologic differentiation. Based on the limited clinical information available in veterinary medicine, the drugs that are effective in human breast cancer, such as cyclophosphamide, 5-fluorouracil, and doxorubicin, may also have a role in the treatment of malignant mammary gland tumors in dogs. Randomized prospective studies are needed, however, to evaluate the efficacy of chemotherapy in dogs with high-risk mammary gland tumors and to determine which drugs and protocols are the most efficacious. Until such studies are performed, the treatment of canine mammary gland tumors will be based on the individual oncologist's understanding of tumor biology, experience, interpretation of the available studies, and a little bit of gut-feeling. Table 2 is a proposal for treatment guidelines for malignant canine mammary gland tumors according to established prognostic factors, results from published veterinary studies, and current recommendations for breast cancer treatment in women.

  13. SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

    PubMed

    Hsieh, Min-Shu; Lee, Yi-Hsuan; Chang, Yih-Leong

    2016-10-01

    Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory.

  14. Effect of Chia oil (Salvia Hispanica) rich in omega-3 fatty acids on the eicosanoid release, apoptosis and T-lymphocyte tumor infiltration in a murine mammary gland adenocarcinoma.

    PubMed

    Espada, C E; Berra, M A; Martinez, M J; Eynard, A R; Pasqualini, M E

    2007-07-01

    We investigated the effects of certain dietary polyunsaturated fatty acids (PUFAs) and related eicosanoids on the growth and metastasis formation of a murine mammary gland adenocarcinoma. Salvia hispanica (ChO) and Carthamus tinctorius (SaO) vegetable oil sources of omega-3 and -6 PUFAs and a commercial diet as control (CO), were used. We analysed fatty acids of neoplastic cells (NC) membranes by GLC; the eicosanoids 12- HETE and 12-HHT (LOX and COX metabolites) by HPLC and apoptosis and T-lymphocyte infiltration by flow cytometry and microscopy. NC from ChO groups showed lower levels of arachidonic acid and of both eicosanoids compared to SaO and CO (p<0.05). The ChO diet decreased the tumor weight and metastasis number (p<0.05). Apoptosis and T-lymphocyte infiltration were higher and mitosis decreased with respect to the other diets (p<0.05). Present data showed that ChO, an ancient and almost unknown source of omega-3, inhibits growth and metastasis in this tumor model.

  15. Data from the Danish veterinary cancer registry on the occurrence and distribution of neoplasms in dogs in Denmark.

    PubMed

    Brønden, L B; Nielsen, S S; Toft, N; Kristensen, A T

    2010-05-08

    From May 15, 2005 to April 15, 2008, 1878 cases of neoplasms in dogs were reported to the web-based Danish Veterinary Cancer Registry. The proportions of malignant (38 per cent) and benign (45 per cent) tumours were similar. The most common malignant neoplasms were adenocarcinomas (21 per cent), mast cell tumours (19 per cent) and lymphomas (17 per cent). The benign neoplasms most commonly encountered were lipomas (24 per cent), adenomas (22 per cent) and histiocytomas (14 per cent). Skin (43 per cent) and the female reproductive system including mammary tissue (28 per cent) were the most common locations of neoplasia. There was a distinct breed predisposition for tumour development, with a high standard morbidity ratio (indicating a higher risk of cancer) for boxers and Bernese mountain dogs. A standard morbidity ratio below 1 was observed in German shepherd dogs and Danish/Swedish farm dogs, suggesting a lower risk of cancer in these breeds.

  16. 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

  17. Prevalence of Glomerulopathies in Canine Mammary Carcinoma

    PubMed Central

    2016-01-01

    The incidence and prevalence of paraneoplastic glomerulopathy, especially associated with carcinoma, are a matter of debate and the causal link between cancer and glomerular diseases remains unclear. The aim of this study was to evaluate renal biopsies of selected bitches with spontaneous mammary gland carcinoma. We hypothesized that dogs with mammary carcinomas would show histologic evidence of glomerular pathology. A prospective study was performed in dogs with naturally occurring mammary carcinoma that were undergoing tumor resection and ovariohysterectomy. We evaluated renal biopsies of 32 bitches with spontaneous mammary gland carcinoma and 11 control dogs without mammary gland neoplasia. Samples were obtained from the left kidney and the biopsy material was divided for light microscopy (LM), immunofluorescence (IF) and transmission electron microscopy (TEM). Light microscopy abnormalities were identified in 78.1% of dogs with mammary carcinoma (n = 25) and in none of the dogs in the control group. Focal glomerular mesangial matrix expansion was the most common alteration (n = 15, 60.0%), but mesangial cell proliferation (n = 9, 36.0%) and focal segmental glomerulosclerosis (n = 9, 36.0%), synechiae (n = 7, 28.0%), and globally sclerotic glomeruli (n = 6, 24.0%) were also frequent in dogs with malignancy. Immunofluorescence microscopy revealed strong IgM staining was demonstrated in 64.3% (n = 18) of carcinoma dogs. Transmission electron microscopy from dogs with carcinoma revealed slight changes, the most frequent of which was faint sub-endothelial and mesangial deposits of electron-dense material (78%). Mesangial cell interpositioning and segmental effacement of podocyte foot processes were identified in some specimens (45%). Changes in the glomerulus and proteinuria are common in dogs with naturally occurring mammary carcinoma and this condition appears to provide an excellent large animal model for cancer-associated glomerulopathy in humans. PMID:27764139

  18. A case of two different tumors in the heart of a dog.

    PubMed

    Grieco, Valeria; Locatelli, Chiara; Riccardi, Elena; Brambilla, Paola

    2008-05-01

    A 9-year-old, spayed, female Maremmano shepherd had a bilateral mastectomy for multiple mammary adenocarcinomas 2 years previous and was referred to the Cardiology Service of the School of Veterinary Medicine of Milan after an acute episode of cardiogenic collapse. Because of severe cardiovascular symptoms and poor prognosis, the dog was euthanized. Necropsy examination revealed the presence of multiple firm grayish neoplastic nodules in the myocardium of the left ventricle and scattered in the pulmonary parenchyma. Neoplastic nodules were also detected in the spleen, pancreas, liver, kidneys, and omentum. Histological examination revealed the coexistence of tubular adenocarcinoma and an undifferentiated sarcoma in the myocardium. Immunohistochemical staining of the sarcoma cells was negative for cytokeratin, desmin, and smooth muscle myosin, thus excluding their epithelial or myoepithelial origin, as well as an origin from smooth muscles cells. These findings, together with the coexpression of vimentin and alpha-smooth muscle actin, suggested that the sarcoma was derived from myofibroblasts. To the authors' knowledge, this is the first report describing cardiac sarcoma of presumptive myofibroblastic origin in a dog with simultaneous occurrence of cardiac metastasis of mammary gland adenocarcinoma.

  19. 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)

  20. Anti-Neoplastic Cytotoxicity of Gemcitabine-(C4-amide)-[anti-EGFR] in Dual-combination with Epirubicin-(C3-amide)-[anti-HER2/neu] against Chemotherapeutic-Resistant Mammary Adenocarcinoma (SKBr-3) and the Complementary Effect of Mebendazole

    PubMed Central

    Coyne, CP; Jones, Toni; Bear, Ryan

    2015-01-01

    Aims Delineate the feasibility of simultaneous, dual selective “targeted” chemotherapeutic delivery and determine if this molecular strategy can promote higher levels anti-neoplastic cytotoxicity than if only one covalent immunochemotherapeutic is selectively “targeted” for delivery at a single membrane associated receptor over-expressed by chemotherapeutic-resistant mammary adenocarcinoma. Methodology Gemcitabine and epirubicin were covalently bond to anti-EGFR and anti-HER2/neu utilizing a rapid multi-phase synthetic organic chemistry reaction scheme. Determination that 96% or greater gemcitabine or epirubicin content was covalently bond to immunoglobulin fractions following size separation by micro-scale column chromatography was established by methanol precipitation analysis. Residual binding-avidity of gemcitabine-(C4-amide)-[anti-EG-FR] applied in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu] was determined by cell-ELIZA utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) populations. Lack of fragmentation or polymerization was validated by SDS-PAGE/immunodetection/chemiluminescent autoradiography. Anti-neoplastic cytotoxic potency was determined by vitality stain analysis of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) monolayers known to uniquely over-express EGFR (2 × 105/cell) and HER2/neu (1 × 106/cell) receptor complexes. The covalent immunochemotherapeutics gemcitabine-(C4-amide)-[anti-EGFR] and epirubicin-(C3-amide)-[anti-HER2/neu] were applied simultaneously in dual-combination to determine their capacity to collectively evoke elevated levels of anti-neoplastic cytotoxicity. Lastly, the tubulin/microtubule inhibitor mebendazole evaluated to determine if it’s potential to complemented the anti-neoplastic cytotoxic properties of gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu]. Results Dual-combination of gemcitabine-(C4-amide)-[anti-EGFR] with

  1. Canine mammary tumour cell lines established in vitro.

    PubMed

    Hellmén, E

    1993-01-01

    Mammary tumours are the most common tumours in the female dog. The tumours have a complex histology and exist in epithelial, mixed and mesenchymal forms. To study the biology of canine mammary tumours, five cell lines have been established and characterized. The results indicate that canine mammary tumours might be derived from mammary stem cells and that the tumour growth is independent of oestrogens. The established canine mammary tumour cell lines will be valuable tools in further studies of the histogenesis and pathogenesis of these tumours.

  2. Mouse mammary tumor virus-like nucleotide sequences in canine and feline mammary tumors.

    PubMed

    Hsu, Wei-Li; Lin, Hsing-Yi; Chiou, Shyan-Song; Chang, Chao-Chin; Wang, Szu-Pong; Lin, Kuan-Hsun; Chulakasian, Songkhla; Wong, Min-Liang; Chang, Shih-Chieh

    2010-12-01

    Mouse mammary tumor virus (MMTV) has been speculated to be involved in human breast cancer. Companion animals, dogs, and cats with intimate human contacts may contribute to the transmission of MMTV between mouse and human. The aim of this study was to detect MMTV-like nucleotide sequences in canine and feline mammary tumors by nested PCR. Results showed that the presence of MMTV-like env and LTR sequences in canine malignant mammary tumors was 3.49% (3/86) and 18.60% (16/86), respectively. For feline malignant mammary tumors, the presence of both env and LTR sequences was found to be 22.22% (2/9). Nevertheless, the MMTV-like LTR and env sequences also were detected in normal mammary glands of dogs and cats. In comparisons of the MMTV-like DNA sequences of our findings to those of NIH 3T3 (MMTV-positive murine cell line) and human breast cancer cells, the sequence similarities ranged from 94 to 98%. Phylogenetic analysis revealed that intermixing among sequences identified from tissues of different hosts, i.e., mouse, dog, cat, and human, indicated the MMTV-like DNA existing in these hosts. Moreover, the env transcript was detected in 1 of the 19 MMTV-positive samples by reverse transcription-PCR. Taken together, our study provides evidence for the existence and expression of MMTV-like sequences in neoplastic and normal mammary glands of dogs and cats.

  3. Mouse Mammary Tumor Virus-Like Nucleotide Sequences in Canine and Feline Mammary Tumors▿

    PubMed Central

    Hsu, Wei-Li; Lin, Hsing-Yi; Chiou, Shyan-Song; Chang, Chao-Chin; Wang, Szu-Pong; Lin, Kuan-Hsun; Chulakasian, Songkhla; Wong, Min-Liang; Chang, Shih-Chieh

    2010-01-01

    Mouse mammary tumor virus (MMTV) has been speculated to be involved in human breast cancer. Companion animals, dogs, and cats with intimate human contacts may contribute to the transmission of MMTV between mouse and human. The aim of this study was to detect MMTV-like nucleotide sequences in canine and feline mammary tumors by nested PCR. Results showed that the presence of MMTV-like env and LTR sequences in canine malignant mammary tumors was 3.49% (3/86) and 18.60% (16/86), respectively. For feline malignant mammary tumors, the presence of both env and LTR sequences was found to be 22.22% (2/9). Nevertheless, the MMTV-like LTR and env sequences also were detected in normal mammary glands of dogs and cats. In comparisons of the MMTV-like DNA sequences of our findings to those of NIH 3T3 (MMTV-positive murine cell line) and human breast cancer cells, the sequence similarities ranged from 94 to 98%. Phylogenetic analysis revealed that intermixing among sequences identified from tissues of different hosts, i.e., mouse, dog, cat, and human, indicated the MMTV-like DNA existing in these hosts. Moreover, the env transcript was detected in 1 of the 19 MMTV-positive samples by reverse transcription-PCR. Taken together, our study provides evidence for the existence and expression of MMTV-like sequences in neoplastic and normal mammary glands of dogs and cats. PMID:20881168

  4. Mammary Analogue Secretory Carcinoma.

    PubMed

    Stevens, Todd M; Parekh, Vishwas

    2016-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined.

  5. 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

  6. Relationships among subgross anatomy, computed tomography, and histologic findings in dogs with disease localized to the pulmonary acini.

    PubMed

    Scrivani, Peter V; Thompson, Margret S; Dykes, Nathan L; Holmes, Nedra L; Southard, Teresa L; Gerdin, Jodie A; Bezuidenhout, Abraham J

    2012-01-01

    During computed tomography (CT), the appearance of disease involving the pulmonary acinus may be described using terms such as atelectasis, ground-glass opacity, or consolidation. These CT signs, however, have not been correlated with histologic findings in canine pulmonary disease. To facilitate interpretation of lung diseases by CT signs, our goals were to review the morphologic organization of the lung and evaluate the medical records of four dogs with different types of pulmonary acinar disease. Anatomic review focused on understanding the pulmonary acinus and the secondary pulmonary lobule; the secondary pulmonary lobule is a fundamental unit for interpretation in people. All dogs had similar CT findings of fully expanded lungs with increased attenuation and partial-to-complete obscuring of the pulmonary blood vessels. Histologic findings varied between dogs and included partial-to-complete filling of airspaces with cells or fluid, interstitial thickening, increased capillary blood volume, or a combination of these findings. Final diagnoses were hemorrhagic pneumonia, bronchiolar carcinoma, metastatic mammary adenocarcinoma, and pulmonary edema. In summary, the morphologic organization of the lungs is complex and has implications for diagnostic interpretation needing further evaluation in dogs. In this study, increased lung attenuation during CT due to disease localized to the pulmonary acini was due to the displacement of air from the lungs and not to the microscopic distribution of lesions within the pulmonary acinus. Imaging descriptors that classify diseases according to structures larger than the pulmonary acini, for example, regions of the secondary pulmonary lobule or larger, may be appropriate for dogs.

  7. 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.

  8. Genetic Mechanisms in Apc-Mediated Mammary Tumorigenesis

    PubMed Central

    Kuraguchi, Mari; Ohene-Baah, Nana Yaw; Sonkin, Dmitriy; Bronson, Roderick Terry; Kucherlapati, Raju

    2009-01-01

    Many components of Wnt/β-catenin signaling pathway also play critical roles in mammary tumor development, yet the role of the tumor suppressor gene APC (adenomatous polyposis coli) in breast oncongenesis is unclear. To better understand the role of Apc in mammary tumorigenesis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-cre and WAP-cre transgenic mice that express Cre-recombinase in mammary progenitor cells and lactating luminal cells, respectively. Only the K14-cre–mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological heterogeneity, suggesting the multilineage progenitor cell origin of these tumors. These tumors harbored truncation mutation in a defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of β-catenin signaling. Activating mutations at codons 12 and 61 of either H-Ras or K-Ras were also found in a subset of these tumors. Expression profiles of acinar-type mammary tumors from K14-cre; ApcCKO/+ mice showed luminal epithelial gene expression pattern, and clustering analysis demonstrated more correlation to MMTV-neu model than to MMTV-Wnt1. In contrast, neither WAP-cre–induced Apc heterozygous nor homozygous mutations resulted in predisposition to mammary tumorigenesis, although WAP-cre–mediated Apc deficiency resulted in severe squamous metaplasia of mammary glands. Collectively, our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of β-catenin signaling optimal for mammary tumor development and explain partially the colon- but not mammary-specific tumor development in patients that carry germline mutations in APC. PMID:19197353

  9. 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

  10. Role of progestin-induced mammary-derived growth hormone in the pathogenesis of cystic endometrial hyperplasia in the bitch.

    PubMed

    Bhatti, Sofie F M; Rao, Nagesha A S; Okkens, Auke C; Mol, Jan A; Duchateau, Luc; Ducatelle, Richard; van den Ingh, Ted S G A M; Tshamala, Mulenda; Van Ham, Luc M L; Coryn, Marc; Rijnberk, Ad; Kooistra, Hans S

    2007-10-01

    Endogenous progesterone and synthetic progestins may induce hypersecretion of growth hormone (GH) of mammary origin, hyperplastic ductular changes in the mammary gland, and the development of cystic endometrial hyperplasia (CEH) in dogs. It was investigated whether progestin-induced mammary GH plays a role in the pathogenesis of CEH in the bitch. During 1 year, bitches with surgically excised mammary glands and healthy control bitches received medroxyprogesterone acetate (MPA). Before and after MPA treatment, uterine and mammary tissues were collected for histological, immunohistochemical, and RT-PCR examination. After MPA administration, the mammary tissue in the control dogs had differentiated into lobulo-alveolar structures and CEH was present in all uteri of both dog groups. In the MPA-exposed mammary tissue of the control dogs, GH could only be demonstrated immunohistochemically in proliferating epithelium. After treatment with MPA the dogs of both groups had immunohistochemically demonstrable GH in the cytoplasm of hyperplastic glandular uterine epithelial cells. RT-PCR analysis of the mammary gland tissue after MPA administration demonstrated a significant higher GH gene, and lower GHR gene expression than before treatment. In the uterus, the expression of the gene encoding for GH was significantly increased in the mastectomized dogs, whereas in the control dogs the expression of the gene encoding for insulin-like growth factor-I had significantly increased with MPA administration. MPA treatment significantly down regulated PR gene expression in the uterus in both dog groups. These results indicate that progestin-induced GH of mammary origin is not an essential component in the development of CEH in the bitch.

  11. Defect of the mitochondrial DNA hypervariable region as a risk factor for canine mammary tumour.

    PubMed

    Surdyka, M; Slaska, B

    2016-05-19

    The aim of this study was to identify mutations in the hypervariable region of mitochondrial DNA in canine mammary tumours and to determine their association with the process of neoplastic transformation. A total of 93 biological samples, including blood as well as normal and neoplastic tissue samples from 31 dogs with diagnosed malignant canine mammary tumours were analysed. DNA extraction, amplification and sequencing of the D-loop as well as bioinformatic and statistical analyses were performed. In the mitochondrial D-loop sequence, 26 polymorphic loci and 5 mutations were identified. For the first time, D-loop length heteroplasmy was detected in dogs with mammary tumours. The malignancy grade exerted no effect on the presence of nucleotide changes. A statistically significant association between the presence of mutations and polymorphisms and the size of dogs was demonstrated. The 100% frequency of length heteroplasmy may imply that this is a hotspot mutation of canine mammary tumour.

  12. Mammary Stem Cell Research in Veterinary Science: An Update

    PubMed Central

    Borena, Bizunesh M.; Bussche, Leen; Burvenich, Christian; Duchateau, Luc

    2013-01-01

    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

  13. Tissue-specific ceruloplasmin gene expression in the mammary gland.

    PubMed Central

    Jaeger, J L; Shimizu, N; Gitlin, J D

    1991-01-01

    Using a ceruloplasmin cDNA clone in RNA blot analysis, a single 3.7 kb ceruloplasmin-specific transcript was detected in rat mammary gland tissue from pregnant and lactating animals. Ceruloplasmin gene expression in the mammary gland was tissue-specific, with no evidence of expression in brain, heart or other extrahepatic tissues. Ceruloplasmin mRNA was also detected in mammary gland tissue from male, virgin female and non-pregnant/multiparous animals, and the abundance of ceruloplasmin-specific transcripts in virgin female rats was independent of their stage of oestrus. In virgin female mammary gland the content of ceruloplasmin mRNA was 20% of that in hepatic tissue from these animals and approx. 2-3-fold greater than that found in mammary gland tissue of pregnant or lactating animals. Development studies revealed ceruloplasmin gene expression in male and female mammary gland by only 2 weeks of age, prior to the onset of puberty. Biosynthetic studies indicated that the ceruloplasmin mRNA in mammary gland tissue was translated into a 132 kDa protein qualitatively similar to that synthesized in liver. By in situ hybridization, ceruloplasmin gene expression was localized to the epithelium lining the mammary gland alveolar ducts, without evidence of expression in the surrounding mesenchyme. Ceruloplasmin gene expression was also detected in a human breast adenocarcinoma cell line and in biopsy tissue from women with invasive ductal carcinoma. Taken together, these data indicate that the mammary gland is a prominent site of extrahepatic ceruloplasmin gene expression and add to the evidence that ceruloplasmin biosynthesis is associated with growth and differentiation in non-hepatic tissues. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:1764031

  14. 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

  15. Occurrence of mammary tumors in beagls given radium-226

    SciTech Connect

    Bruenger, F.W.; Lloyd, R.D.; Miller, S.C.; Taylor, G.N.; Angus, W.; Huth, D.A.

    1994-06-01

    A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with {sup 226}Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given {sup 226}Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon {yields} polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. 27 refs., 5 figs., 4 tabs.

  16. 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).

  17. [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.

  18. Malignant canine mammary tumours: Preliminary genomic insights using oligonucleotide array comparative genomic hybridisation analysis.

    PubMed

    Santos, Marta; Dias-Pereira, Patrícia; Williams, Christina; Lopes, Carlos; Breen, Matthew

    2017-03-28

    Neoplastic mammary disease in female dogs represents a major health concern for dog owners and veterinarians, but the genomic basis of the disease is poorly understood. In this study, we performed high resolution oligonucleotide array comparative genomic hybridisation (oaCGH) to assess genome wide DNA copy number changes in 10 malignant canine mammary tumours from seven female dogs, including multiple tumours collected at one time from each of three female dogs. In all but two tumours, genomic imbalances were detected, with losses being more common than gains. Canine chromosomes 9, 22, 26, 27, 34 and X were most frequently affected. Dissimilar oaCGH ratio profiles were observed in multiple tumours from the same dogs, providing preliminary evidence for probable independent pathogenesis. Analysis of adjacent samples of one tumour revealed regional differences in the number of genomic imbalances, suggesting heterogeneity within tumours.

  19. 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.

  20. /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)

  1. Relationship between major histocompatibility complex class I expression and prognosis in canine mammary gland tumors.

    PubMed

    Tanaka, Toshiyuki; Shimada, Terumasa; Akiyoshi, Hideo; Shimizu, Junichiro; Zheng, Cao; Yijyun, Li; Mie, Keiichiro; Hayashi, Akiyoshi; Kuwamura, Mitsuru; Hoshi, Fumio; Ohashi, Fumihito

    2013-10-01

    The aim of this study was to evaluate MHC class I expression and prognosis using tumor tissues surgically removed from 9 dogs with mammary gland carcinomas and from 13 dogs with complex carcinomas. We assessed MHC class I expression and its correlation with tumor size, B2M expression, infiltration of lymphocytes, histological grade and prognosis. Hematoxylin and eosin-stained sections were histologically graded using the Elston and Ellis grading method. MHC class I expression on tumor cells was evaluated using the avidin-biotin peroxidase complex method. Loss of MHC class I expression from canine mammary gland carcinomas was significantly correlated with poor prognosis (P<0.05). Loss of MHC class I expression showed no association with poor prognosis in canine mammary gland complex carcinomas, because the data were not balanced. Only 1 of 13 (7.6%) canine mammary gland complex carcinomas showed loss of MHC class I expression. All 13 of these dogs showed good prognosis. Thus, the low frequency of MHC class I expression loss from canine mammary gland complex carcinomas may be associated with good prognosis. Taken together, these results suggest that loss of MHC class I expression may be associated with poor prognosis in canine mammary gland carcinomas.

  2. Differential transformation of mammary epithelial cells by Wnt genes.

    PubMed Central

    Wong, G T; Gavin, B J; McMahon, A P

    1994-01-01

    The mouse Wnt family includes at least 10 genes that encode structurally related secreted glycoproteins. Wnt-1 and Wnt-3 were originally identified as oncogenes activated by the insertion of mouse mammary tumor virus in virus-induced mammary adenocarcinomas, although they are not expressed in the normal mammary gland. However, five other Wnt genes are differentially expressed during development of adult mammary tissue, suggesting that they may play distinct roles in various phases of mammary gland growth and development. Induction of transformation by Wnt-1 and Wnt-3 may be due to interference with these normal regulatory events; however, there is no direct evidence for this hypothesis. We have tested Wnt family members for the ability to induce transformation of cultured mammary cells. The results demonstrate that the Wnt gene family can be divided into three groups depending on their ability to induce morphological transformation and altered growth characteristics of the C57MG mammary epithelial cell line. Wnt-1, Wnt-3A, and Wnt-7A were highly transforming and induced colonies which formed and shed balls of cells. Wnt-2, Wnt-5B, and Wnt-7B also induced transformation but with a lower frequency and an apparent decrease in saturation density. In contrast, Wnt-6 and two other family members which are normally expressed in C57MG cells, Wnt-4 and Wnt-5A, failed to induce transformation. These data demonstrate that the Wnt genes have distinct effects on cell growth and should not be regarded as functionally equivalent. Images PMID:8065359

  3. Mammary Duct Ectasia

    MedlinePlus

    ... tenderness or inflammation of the clogged duct (periductal mastitis). Mammary duct ectasia most often occurs in women ... that's turned inward (inverted) A bacterial infection called mastitis also may develop in the affected milk duct, ...

  4. Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate.

    PubMed

    Lamartiniere, Coral A; Cotroneo, Michelle S; Fritz, Wayne A; Wang, Jun; Mentor-Marcel, Roycelynn; Elgavish, Ada

    2002-03-01

    We investigated the potential of genistein, the primary isoflavone of soy, to protect against breast and prostate cancers in animal models. For mammary cancer studies, Sprague-Dawley rats were fed AIN-76A diet plus minus 250 mg genistein/kg diet. Dimethylbenz[a]anthracene was administered by gavage at d 50 postpartum to induce mammary tumors. Mammary cancer chemoprevention was demonstrated after prepubertal and combined prepubertal and adult genistein treatments but not after prenatal- or adult-only treatments, demonstrating that the timing of exposure to genistein is important for mammary cancer chemoprevention. The cellular mechanism of action was found to be mammary gland and cell differentiation, as shown by whole-mount analysis and beta-casein expression. An imprinting effect was shown for epidermal growth factor receptor expression in mammary terminal end buds. For prostate cancer studies, we used two models. The first was a chemically (N-methylnitrosourea) induced prostate cancer rat model. Genistein in the diet inhibited the development of invasive adenocarcinomas in a dose-dependent manner. The second model was a transgenic mouse model that resulted in spontaneously developing adenocarcinoma tumor of the prostate. Genistein in the diet reduced the incidence of poorly differentiated prostatic adenocarcinomas in a dose-dependent manner and down-regulated androgen receptor, estrogen receptor-alpha, progesterone receptor, epidermal growth factor receptor, insulin-like growth factor-I, and extracellular signal-regulated kinase-1 but not estrogen receptor-beta and transforming growth factor-alpha mRNA expressions. We conclude that dietary genistein protects against mammary and prostate cancers by regulating specific sex steroid receptors and growth factor signaling pathways.

  5. Increased levels of interleukins 8 and 10 as findings of canine inflammatory mammary cancer.

    PubMed

    de Andrés, Paloma Jimena; Illera, Juan Carlos; Cáceres, Sara; Díez, Lucía; Pérez-Alenza, Maria Dolores; Peña, Laura

    2013-04-15

    Inflammatory mammary cancer (IMC) is a distinct form of mammary cancer that affects dogs and women [in humans, IMC is known as inflammatory breast cancer (IBC)], and is characterized by a sudden onset and an aggressive clinical course. Spontaneous canine IMC shares epidemiologic, histopathological and clinical characteristics with the disease in humans and has been proposed as the best spontaneous animal model for studying IBC, although several aspects remain unstudied. Interleukins (ILs) play an important role in cancer as potential modulators of angiogenesis, leukocyte infiltration and tumor growth. The aims of the present study were to assess serum and tumor levels of several ILs (IL-1α, IL-1β, IL-6, IL-8 and IL-10) by enzyme-immunoassay in dogs bearing benign and malignant mammary tumors, including dogs with IMC, for a better understanding of this disease. Forty-eight dogs were prospectively included. Animals consisted of 7 healthy Beagles used as donors for normal mammary glands (NMG) and serum controls (SCs), 10 dogs with hyperplasias and benign mammary tumors (HBMT), 24 with non-inflammatory malignant mammary tumors (non-IMC MMT) and 7 dogs with clinical and pathological IMC. IL-8 (serum) and IL-10 (serum and tissue homogenate) levels were higher in the dogs with IMC compared with the non-IMC MMT group. ILs were increased with tumor malignancy as follows: in tumor homogenates IL-6 levels were higher in malignant tumors (IMC and non-IMC MMT) versus HBMT and versus NMG and tumor IL-8 was increased in malignant tumors versus NMG; in serum, IL-1α and IL-8 levels were higher in the malignant groups respect to HBMT and SCs; interestingly, IL-10 was elevated only in the serum of IMC animals. To the best of our knowledge, this is the first report that analyzes ILs in IMC and IL-10 in canine mammary tumors. Our results indicate a role for IL-6, IL-8 and IL-10 in canine mammary malignancy and specific differences in ILs content in IMC versus non-IMC MMT that could

  6. Molecular Analysis of Motility in Metastatic Mammary Adenocarcinoma Cells

    DTIC Science & Technology

    1998-09-01

    has been identified as a good candidate for nucleation of actin filaments in vivo. Originally identified from the cortex of Acanthamoeba (111), it... Acanthamoeba to mammalian fibroblasts (40,112,113). Furthermore, the Arp2/3 complex can 38 specifically induce actin polymerization and nucleation at the

  7. Primary appendiceal mucinous adenocarcinoma.

    PubMed

    Behera, Prativa Kumari; Rath, Pramod Kumar; Panda, Rabiratna; Satpathi, Sanghamitra; Behera, Rajan

    2011-04-01

    Primary Adenocarcinomas of the appendix are extremely rare tumor. We report a case of primary mucinous adenocarcinoma in a 40 year old lady misdiagnosed as having acute appendicitis. All the routine investigations were within normal limit. USG of abdomen showed dilated appendix with little fluid collection adjacent to it and no other abnormality was seen which suggested acute appendicitis. Appendicectomy was done and excised appendix was sent for histopathological examination. Mucinous Adenocarcinoma of the appendix was confirmed after histopathological examination. Right hemicolectomy was done as a second stage procedure. As some cases are incidentally discovered, this case emphasizes that histological examination of all appendicectomy specimens is mandatory.

  8. Small Bowel Adenocarcinoma.

    PubMed

    Aparicio, Thomas; Zaanan, Aziz; Mary, Florence; Afchain, Pauline; Manfredi, Sylvain; Evans, Thomas Ronald Jeffry

    2016-09-01

    Small bowel adenocarcinomas (SBAs) are rare tumors, but their incidence is increasing. The most common primary location is the duodenum. Even though SBAs are more often sporadic, some diseases are risk factors. Early diagnosis of small bowel adenocarcinoma remains difficult, despite significant radiologic and endoscopic progress. After R0 surgical resection, the main prognostic factor is lymph node invasion. An international randomized trial (BALLAD [Benefit of Adjuvant Chemotherapy For Small Bowel Adenocarcinoma] study) will evaluate the benefit of adjuvant chemotherapy. For metastatic disease, retrospectives studies suggest that platinum-based chemotherapy is the most effective treatment. Phase II studies are ongoing to evaluate targeted therapy in metastatic SBA.

  9. Adenocarcinoma of the urinary bladder.

    PubMed

    Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

    2015-01-01

    Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma.

  10. Adenocarcinoma of the urinary bladder

    PubMed Central

    Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

    2015-01-01

    Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma. PMID:26309895

  11. Prostate Ductal Adenocarcinoma.

    PubMed

    Amin, Ali

    2017-03-30

    Prostate ductal adenocarcinoma (PDA) is a rare subtype of prostate adenocarcinoma that shows more aggressive behavior than conventional prostatic acinar adenocarcinoma. PDA demonstrates similar clinical and paraclinical features such as prostatic acinar adenocarcinoma; therefore, clinical distinction of the 2 entities is very difficult (if not impossible) and histopathology plays an important role in the diagnosis of the disease. This review discusses all the necessary information needed for the diagnosis and prognosis of PDA including the morphologic features of PDA, an introduction about the known variants of PDA with helpful hints in grading of each variant, tips on differential diagnosis of PDA from the common morphologic mimickers, a detailed discussion on the value of immunohistochemistry in the diagnosis of PDA, and pathologic features that are helpful in determining the outcome.

  12. 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

  13. Mammary gland development.

    PubMed

    Macias, Hector; Hinck, Lindsay

    2012-01-01

    The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial–mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development—pubertal growth, pregnancy, lactation, and involution—occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone (GH) and estrogen, as well as insulin-like growth factor 1 (IGF1), to create a ductal tree that fills the fat pad. Upon pregnancy, the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its prepregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease.

  14. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats

    PubMed Central

    Kakehashi, Anna; Yoshida, Midori; Tago, Yoshiyuki; Ishii, Naomi; Okuno, Takahiro; Gi, Min; Wanibuchi, Hideki

    2016-01-01

    Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3%, and more pronouncedly, at 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA. PMID:27827907

  15. Identification and characterization of cancer stem cells in canine mammary tumors.

    PubMed

    Rybicka, Agata; Król, Magdalena

    2016-12-19

    Cancer stem cells (CSC) represent a small subpopulation of cells in malignant tumors that possess the unique ability to self-renew, differentiate and resist chemo- and radiotherapy. These cells have been postulated to be the basis for some of the difficulties in treating cancer, and therefore, numerous approaches have been developed to specifically target and eliminate CSC in diverse types of cancer, including breast cancer. Spontaneously occurring mammary tumors in canines share clinical and molecular similarities with the human counterpart, making the dog a potentially powerful model for the study of human breast cancer and clinical trials. Studies focused on canine mammary CSC might therefore enhance our understanding of the biology and possible treatment of the disease in both dogs and humans. In this review, we discuss various approaches currently in use to isolate and characterize canine mammary CSC.

  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.

  17. Prognostic studies of canine and feline mammary tumours: the need for standardized procedures.

    PubMed

    Matos, A J F; Baptista, C S; Gärtner, M F; Rutteman, G R

    2012-07-01

    For several years, veterinary oncologists have been struggling with the prognosis of mammary tumours in dogs and cats. Translation of tumour characteristics into prognostic information is an invaluable tool for the use of the most appropriate therapies, as well as for planning innovative therapeutic trials. Moreover, canine and feline spontaneous mammary gland tumours are good models for the study of human breast cancer. Collecting and interpreting information regarding the prognosis of canine and feline mammary tumours is difficult due to the fact that different methods have been applied to study various components and characteristics. This review identifies some of the challenges of prognostic studies of spontaneous canine and feline mammary tumours and suggests standardized procedures to overcome these challenges and facilitate reproducibility and assessment of results.

  18. Paracrine Overexpression of Insulin-Like Growth Factor-1 Enhances Mammary Tumorigenesis in Vivo

    PubMed Central

    de Ostrovich, Krisztina Kovács; Lambertz, Isabel; Colby, Jennifer K. L.; Tian, Jie; Rundhaug, Joyce E.; Johnston, Dennis; Conti, Claudio J.; DiGiovanni, John; Fuchs-Young, Robin

    2008-01-01

    Insulin-like growth factor-1 (IGF-1) stimulates proliferation, regulates tissue development, protects against apoptosis, and promotes the malignant phenotype in the breast and other organs. Some epidemiological studies have linked high circulating levels of IGF-1 with an increased risk of breast cancer. To study the role of IGF-1 in mammary tumorigenesis in vivo, we used transgenic mice in which overexpression of IGF-1 is under the control of the bovine keratin 5 (BK5) promoter and is directed to either the myoepithelial or basal cells in a variety of organs, including the mammary gland. This model closely recapitulates the paracrine exposure of breast epithelium to stromal IGF-1 seen in women. Histologically, mammary glands from transgenic mice were hyperplastic and highly vascularized. Mammary glands from prepubertal transgenic mice had significantly increased ductal proliferation compared with wild-type tissues, although this difference was not maintained after puberty. Transgenic mice also had increased susceptibility to mammary carcinogenesis, and 74% of the BK5.IGF-1 mice treated with 7,12-dimethylbenz[a]anthracene (20 μg/day) developed mammary tumors compared with 29% of the wild-type mice. Interestingly, 31% of the vehicle-treated BK5.IGF-1 animals, but none of the wild-type animals, spontaneously developed mammary cancer. The mammary tumors were moderately differentiated adenocarcinomas that expressed functional, nuclear estrogen receptor at both the protein and mRNA levels. These data support the hypothesis that tissue overexpression of IGF-1 stimulates mammary tumorigenesis. PMID:18688034

  19. 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

  20. Humanization of the mouse mammary gland.

    PubMed

    Wronski, A; Arendt, L M; Kuperwasser, Charlotte

    2015-01-01

    Although mouse models have provided invaluable information on the mechanisms of mammary gland development, anatomical and developmental differences between human and mice limit full understanding of this fundamental process. Humanization of the mouse mammary gland by injecting immortalized human breast stromal cells into the cleared murine mammary fat pad enables the growth and development of human mammary epithelial cells or tissue. This facilitates the characterization of human mammary gland development or tumorigenesis by utilizing the mouse mammary fat pad. Here we describe the process of isolating human mammary stromal and epithelial cells as well as their introduction into the mammary fat pads of immunocompromised mice.

  1. 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.

  2. Modulation of Notch Signaling Elicits Signature Tumors and Inhibits Hras1-Induced Oncogenesis in the Mouse Mammary Epithelium

    PubMed Central

    Kiaris, Hippokratis; Politi, Katerina; Grimm, Lisa M.; Szabolcs, Matthias; Fisher, Peter; Efstratiadis, Argiris; Artavanis-Tsakonas, Spyros

    2004-01-01

    Deregulation of Notch signaling, which normally affects a broad spectrum of cell fates, has been implicated in various neoplastic conditions. Here we describe a transgenic mouse model, which demonstrates that expression of a constitutively active form of the Notch1 receptor in the mammary epithelium induces the rapid development of pregnancy/lactation-dependent neoplasms that consistently exhibit a characteristic histopathological pattern. These signature tumors retain the ability to respond to apoptotic stimuli and regress on initiation of mammary gland involution, but eventually appear to progress in subsequent pregnancies to nonregressing malignant adenocarcinomas. Additionally, we present evidence indicating that cyclin D1 is an in vivo target of Notch signals in the mammary glands and demonstrate that we can effectively inhibit Hras1-driven, cyclin D1-dependent mammary oncogenesis by transgenic expression of the Notch antagonist Deltex. PMID:15277242

  3. 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.

  4. Physiologically activated mammary fibroblasts promote postpartum mammary cancer

    PubMed Central

    Guo, Qiuchen; Burchard, Julja; Spellman, Paul

    2017-01-01

    Women diagnosed with breast cancer within 5 years of childbirth have poorer prognosis than nulliparous or pregnant women. Weaning-induced breast involution is implicated, as the collagen-rich, immunosuppressive microenvironment of the involuting mammary gland is tumor promotional in mice. To investigate the role of mammary fibroblasts, isolated mammary PDGFRα+ cells from nulliparous and postweaning mice were assessed for activation phenotype and protumorigenic function. Fibroblast activation during involution was evident by increased expression of fibrillar collagens, lysyl oxidase, Tgfb1, and Cxcl12 genes. The ability of mammary tumors to grow in an isogenic, orthotopic transplant model was increased when tumor cells were coinjected with involution-derived compared with nulliparous-derived mammary fibroblasts. Mammary tumors in the involution-fibroblast group had increased Ly6C+ monocytes at the tumor border, and decreased CD8+ T cell infiltration and tumor cell death. Ibuprofen treatment suppressed involution-fibroblast activation and tumor promotional capacity, concurrent with decreases in tumor Ly6C+ monocytes, and increases in intratumoral CD8+ T cell infiltration, granzyme levels, and tumor cell death. In total, our data identify a COX/prostaglandin E2 (PGE2)–dependent activated mammary fibroblast within the involuting mammary gland that displays protumorigenic, immunosuppressive activity, identifying fibroblasts as potential targets for the prevention and treatment of postpartum breast cancer. PMID:28352652

  5. Morphological and immunohistochemical characterization of spontaneous mammary tumours in European hedgehogs (Erinaceus europaeus).

    PubMed

    Döpke, C; Fehr, M; Thiele, A; Pohlenz, J; Wohlsein, P

    2007-07-01

    Mammary tumour samples (11 surgical and five post-mortem) from 16 adult European hedgehogs submitted between 1980 and 2004 were examined. Histologically, the tumours were classified as simple tubulo-papillary carcinomas with local invasive growth. In six cases, tumour cell emboli were present in blood vessels or lymphatic vessels, or both. However, metastasis to regional lymph nodes was found only in one hedgehog. Malignant neoplastic epithelial cells were immunolabelled by antibodies specific for various cytokeratins (CKs), including CK1-8, 10, 13-16, 19 and 20. CK expression did not differ from that in normal mammary gland tissue. CK20 was expressed in the mammary tissue of hedgehogs, in contrast to that of dogs and cats; CK7 immunolabelling, however, which commonly occurs in mammary epithelial cells, was negative. CK20 expression, together with the lack of CK7 as determined by a protein-specific antibody, represented an important difference from the CK profile shown by mammary epithelial cells of other mammalian species, including the dog and cat.

  6. On the possible role of mammary-derived growth hormone in human breast cancer.

    PubMed

    Thijssen, Jos H H

    2009-12-01

    The incidence of breast cancer has risen worldwide, especially in countries where it used to be low, very probably as a result of economic prosperity and changes in life-style. In women, the available data have resulted in the concept of progression from normal breast development to cancer through precursor lesions sensitive to hormones and growth factors that can be produced locally in the mammary gland, acting as paracrine or autocrine stimulating agents. The local endocrine environment in the breast can be different from the situation in the circulation. In the dog, growth hormone (GH) can be produced locally in the mammary glands and its production can be stimulated by progestins. This GH probably plays a paracrine role in the progesterone-induced proliferation and differentiation of mammary epithelium. There is increasing evidence that the local mammary progestin/GH-axis is operational not only in dogs but also in human breast cancer. No data are yet available on the production of mammary-derived GH in women.

  7. Primary mammary mucinous cystadenocarcinoma: cytological and histological findings.

    PubMed

    Sentani, Kazuhiro; Tashiro, Takashi; Uraoka, Naohiro; Aosaki, Yoriyuki; Yano, Satomi; Takaeko, Fumio; Yasui, Wataru

    2012-07-01

    Mucinous cystadenocarcinoma (MCA), commonly encountered in the ovary or pancreas, is rare in the breast and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. Only 11 cases of primary mammary MCA have been reported. In this article, we report a case of primary mammary MCA with focus on cytological and histological findings. A 65-year-old female noticed right palpable breast mass. Sonography showed an irregularly shaped 2.8 × 2.4 cm lesion in the upper outer quadrant of the right breast. Fine-needle aspiration cytology was performed on the right breast nodule, and cytopathologic examination suggested an adenocarcinoma composed of tall columnar cells with mucin. A partial mastectomy of the right breast and the axillary lymph nodes dissection was performed. The gross examination revealed a well-demarcated and mucus-filled tumor. Histologically, it had complex papillae, some of which were supported by delicate fibrovascular stroma lined by simple to slightly stratified columnar neoplastic epithelial cells with intracellular mucin, coexisting with MCA in situ and ordinary intraductal carcinoma component (ICC). Immunohistochemically, ICC was HER2-negative and estrogen receptor/progesterone receptor-positive, while MCA was triple negative. MCA might be derived from a metaplasia of ordinary ICC, but its pathogenesis and biologic behavior remains unclear. Despite the invasive nature of mammary MCA, these carcinomas appear to be associated with a good prognosis. The patient has remained well and disease-free for 6 months after the operation.

  8. MicroRNA expression in canine mammary cancer.

    PubMed

    Boggs, R Michelle; Wright, Zachary M; Stickney, Mark J; Porter, Weston W; Murphy, Keith E

    2008-08-01

    MicroRNAs (miRNAs) are 18-22-nt noncoding RNAs that are involved in post-transcriptional regulation of genes. Oncomirs, a subclass of miRNAs, include genes whose expression, or lack thereof, are associated with cancers. Until the last decade, the domestic dog was an underused model for the study of various human diseases that have genetic components. The dog exhibits marked genetic and physiologic similarity to the human, thereby making it an excellent model for study and treatment of various hereditary diseases. Furthermore, because the dog presents with distinct, spontaneously occurring mammary tumors, it may serve as a model for genetic analysis and treatments of humans with malignant breast tumors. Because miRNAs have been found to act as both tumor suppressors and oncogenes in several different cancers, expression patterns of ten miRNAs (miR-15a, miR-16, miR-17-5p, miR-21, miR-29b, miR-125b, miR-145, miR-155, miR-181b, let-7f) known to be associated with human breast cancers were compared to malignant canine mammary tumors (n = 6) and normal canine mammary tissue (n = 10). Resulting data revealed miR-29b and miR-21 to have a statistically significant (p < 0.05 by MANOVA analysis) upregulation in cancerous samples. The ten canine miRNAs follow the same pattern of expression as in the human, except for miR-145 which does not show a difference in expression between the normal and cancerous canine samples. In addition, when analyzed according to specific cancer phenotypes, miR-15a and miR-16 show a significant downregulation in canine ductal carcinomas while miRsR-181b, -21, -29b, and let-7f show a significant upregulation in canine tubular papillary carcinomas.

  9. Ductal barriers in mammary epithelium

    PubMed Central

    Owens, Mark B; Hill, Arnold DK; Hopkins, Ann M

    2013-01-01

    Tissue barriers play an integral role in the biology and pathobiology of mammary ductal epithelium. In normal breast physiology, tight and adherens junctions undergo dynamic changes in permeability in response to hormonal and other stimuli, while several of their proteins are directly involved in mammary tumorigenesis. This review describes first the structure of mammary ductal epithelial barriers and their role in normal mammary development, examining the cyclical changes in response to puberty, pregnancy, lactation and involution. It then examines the role of adherens and tight junctions and the participation of their constituent proteins in mammary tumorigenic functions such as migration, invasion and metastasis. Finally, it discusses the potential of these adhesion proteins as both prognostic biomarkers and potential therapeutic targets in breast cancer. PMID:24665412

  10. Villoglandular papillary adenocarcinoma: case report

    PubMed Central

    Salek, Ghizlane; Lalya, Issam; Rahali, Driss Moussaoui; Dehayni, Mohamed

    2016-01-01

    Villoglandular papillary adenocarcinoma (VPA) is a very rare subtype of adenocarcinoma of the uterine cervix, but a well-recognized variant of cervical adenocarcinoma with a favorable prognosis and generally occurring in women of child-bearing age. Herein, we report a case of VPA diagnosed and managed successfully with conservative measure. This management is particularly desirable in young women to preserve reproductive capability. PMID:28293348

  11. Wwox inactivation enhances mammary tumorigenesis.

    PubMed

    Abdeen, S K; Salah, Z; Maly, B; Smith, Y; Tufail, R; Abu-Odeh, M; Zanesi, N; Croce, C M; Nawaz, Z; Aqeilan, R I

    2011-09-08

    Breast cancer is the leading cause of cancer-related death in women worldwide. Expression of the WWOX tumor suppressor is absent or reduced in a large proportion of breast tumors suggesting that loss of WWOX may contribute to breast tumorigenesis. Wwox-deficient mice die by 3-4 weeks of age precluding adult tumor analysis. To evaluate the effect of WWOX-altered expression on mammary tumor formation, the Wwox-heterozygous allele was back crossed onto the C3H mammary tumor-susceptible genetic background (Wwox(C3H)+/-) and incidence of mammary tumor formation was evaluated. Although 50% of the female Wwox(C3H)+/- mice developed mammary carcinomas, only 7% of Wwox(C3H)+/+ mice did. Intriguingly, mammary tumors in Wwox(C3H)+/- mice frequently lost WWOX protein expression suggesting a genetic predisposition toward mammary tumorigenesis. Immunohistochemical staining of hormone receptors revealed loss of estrogen receptor-α (ER) and progesterone receptor in the majority of these tumors. In vitro, depletion of WWOX in MCF7 ER-positive cells led to reduced ER expression and reduced sensitivity to tamoxifen and estrogen treatment and was associated with enhanced survival and anchorage-independent growth. Finally, cDNA array analyses of murine normal mammary epithelial cells and mammary tumors identified 163 significantly downreguated and 129 upregulated genes in the tumors. The majority of differentially expressed genes were part of pathways involved in cellular movement, cell-to-cell signaling and interaction, cellular development, cellular growth and proliferation and cell death. These changes in gene expression of mouse mammary tumors in Wwox(C3H)+/- mice resemble, at least in part, human breast cancer development. Our findings demonstrate the critical role that the WWOX tumor suppressor gene has in preventing tumorigenesis in breast cancer.

  12. Genetic instability favoring transversions associated with ErbB2-induced mammary tumorigenesis.

    PubMed

    Liu, Shiquan; Liu, Wenjing; Jakubczak, John L; Erexson, Gregory L; Tindall, Kenneth R; Chan, Richard; Muller, William J; Adhya, Sankar; Garges, Susan; Merlino, Glenn

    2002-03-19

    It has been argued that genetic instability is required to generate the myriad mutations that fuel tumor initiation and progression and, in fact, patients with heritable cancer susceptibility syndromes harbor defects in specific genes that normally maintain DNA integrity. However, the vast majority of human cancers arise sporadically, in the absence of deficiencies in known "mutator" genes. We used a cII-based mutation detection assay to show that the mean frequency of forward mutations in primary mammary adenocarcinomas arising in mouse mammary tumor virus-c-erbB2 transgenic mice harboring multiple copies of the lambda bacteriophage genome was significantly higher than in aged-matched, wild-type mammary tissue. Analysis of the cII mutational spectrum within the mammary tumor genomic DNA demonstrated a >6-fold elevation in transversion mutation frequency, resulting in a highly unusual inversion of the transition/transversion ratio characteristic of normal epithelium; frameshift mutation frequencies were unaltered. Arising oncogenic point mutations within the c-erbB2 transgene of such tumors were predominantly transversions as well. Data from this model system support the notion that elaboration of a mutator phenotype is a consequential event in breast cancer and suggest that a novel DNA replication/repair gene is a relatively early mutational target in c-erbB2-induced mammary tumorigenesis.

  13. Experimental mammary carcinogenesis - Rat models.

    PubMed

    Alvarado, Antonieta; Faustino-Rocha, Ana I; Colaço, Bruno; Oliveira, Paula A

    2017-03-15

    Mammary cancer is one of the most common cancers, victimizing more than half a million of women worldwide every year. Despite all the studies in this field, the current therapeutic approaches are not effective and have several devastating effects for patients. In this way, the need to better understand the mammary cancer biopathology and find effective therapies led to the development of several rodent models over years. With this review, the authors intended to provide the readers with an overview of the rat models used to study mammary carcinogenesis, with a special emphasis on chemically-induced models.

  14. Mammary analogue secretory carcinoma mimicking salivary adenoma.

    PubMed

    Williams, Lindsay; Chiosea, Simion I

    2013-12-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor characterized by ETV6 translocation. It appears that prior studies have identified MASC by reviewing salivary gland carcinomas, such as acinic cell carcinoma and adenocarcinoma, not otherwise specified. To address the possibility of MASC mimicking benign salivary neoplasms we reviewed 12 salivary gland (cyst)adenomas diagnosed prior to the discovery of MASC. One encapsulated (cyst)adenoma of the parotid gland demonstrated features of MASC. The diagnosis was confirmed by fluorescence in situ hybridization with an ETV6 break-apart probe. An unusual complex pattern of ETV6 rearrangement with duplication of the telomeric/distal ETV6 probe was identified. This case illustrates that MASC may mimic salivary (cyst)adenomas. To more accurately assess true clinical and morphologic spectrum of MASC, future studies may have to include review of salivary (cyst)adenomas. The differential diagnosis of MASC may have to be expanded to include cases resembling salivary (cyst)adenomas.

  15. Searching for mammary analogue [corrected] secretory carcinoma of salivary gland among its mimics.

    PubMed

    Pinto, Andre; Nosé, Vania; Rojas, Claudia; Fan, Yao-Shan; Gomez-Fernandez, Carmen

    2014-01-01

    Mammary analog secretory carcinoma of salivary gland is a recently described entity with unique morphologic, clinical, and genetic characteristics, including the characteristic t(12;15)(p13;q25) with ETV6-NTRK3 translocation found in secretory carcinomas of the breast. Before their initial description, these salivary gland tumors were generally diagnosed as acinic cell carcinoma or adenocarcinoma. For the purpose of this study, all cases of salivary gland acinic cell carcinoma, cribriform cystadenocarcinoma, and adenocarcinoma, not otherwise specified (NOS), diagnosed over a 10-year period were retrieved from our surgical pathology files. There were a total of 11 cases diagnosed as acinic cell carcinoma, 10 cases of adenocarcinoma, NOS, and 6 cases of cribriform cystadenocarcinoma. All slides were reviewed by two pathologists (AP, CGF) and tumors that show morphologic features of mammary analog secretory carcinoma according to the recent literature were selected. This process narrowed down the initial number to six cases originally diagnosed as acinic cell carcinoma, three cases originally diagnosed as adenocarcinoma, NOS, and one case originally diagnosed as cribriform cystadenocarcinoma. The 10 cases were subjected to immunohistochemistry for S-100, mammaglobin, and ANO1, as well as fluorescence in situ hybridization analysis for t(12;15)(p13;q25) with ETV6-NTRK3 fusion rearrangement. The ETV6-NTRK3 gene rearrangement was detected in three tumors. These three tumors, initially diagnosed as acinic cell carcinomas, stained positive for S-100 and mammaglobin, and negative for ANO1 by immunohistochemistry. Two of the three patients were male (2/3). In summary, mammary analog secretory carcinoma is a newly described diagnostic entity that should be in the differential diagnosis of salivary gland tumors that morphologically mimic other neoplasms, mainly acinic cell carcinomas. They differ from conventional acinic cell tumors immunohistochemically and molecularly

  16. Cat and Dog Bites

    MedlinePlus

    ... Prevention and Wellness Staying Healthy Pets and Animals Cat and Dog Bites Cat and Dog Bites Pets and AnimalsPrevention and WellnessStaying Healthy Share Cat and Dog Bites Cat and dog bites are ...

  17. A simple ductal mammary papilloma in a male maned wolf (Chrysocyon brachyurus).

    PubMed

    Cassali, Geovanni D; Bertagnolli, Angélica C; Ferreira, Enio; Malta, Marcelo C C

    2009-01-01

    A 1-cm-diameter nodule was identified in the left inguinal mammary gland of a 9-year-old male maned wolf (Chrysocyon brachyurus). The mass was surgically excised and examined histologically. Microscopically, the neoplasm consisted of papillary proliferations of epithelial cells on well-defined fibrovascular stalks. A myoepithelial layer was located between the single layer of epithelial cells and the fibrovascular stalk. This histologic appearance was compatible with a diagnosis of simple ductal mammary papilloma. Immunohistochemical staining was positive for p63, cytokeratins AE1/AE3, and estrogen receptors. The clinical and histologic observations in the present case indicate that male maned wolves may develop mammary tumors that are similar to those observed in domestic dogs and humans.

  18. Utility of mammaglobin immunohistochemistry as a proxy marker for the ETV6-NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma.

    PubMed

    Bishop, Justin A; Yonescu, Raluca; Batista, Denise; Begum, Shahnaz; Eisele, David W; Westra, William H

    2013-10-01

    Mammary analogue secretory carcinoma is a recently described salivary gland neoplasm defined by ETV6-NTRK3 gene fusion. Mammary analogue secretory carcinoma's morphology is not entirely specific and overlaps with other salivary gland tumors. Documenting ETV6 rearrangement is confirmatory, but most laboratories are not equipped to perform this test. As mammary analogue secretory carcinomas are positive for mammaglobin, immunohistochemistry could potentially replace molecular testing as a confirmatory test, but the specificity of mammaglobin has not been evaluated across a large and diverse group of salivary gland tumors. One hundred thirty-one salivary gland neoplasms were evaluated by routine microscopy, mammaglobin immunohistochemistry, and ETV6 break-apart fluorescent in situ hybridization. The cases included 15 mammary analogue secretory carcinomas, 44 adenoid cystic carcinomas, 33 pleomorphic adenomas, 18 mucoepidermoid carcinomas, 10 acinic cell carcinomas, 4 adenocarcinomas not otherwise specified, 3 polymorphous low-grade adenocarcinomas, 3 salivary duct carcinomas, and 1 low-grade cribriform cystadenocarcinoma. All 15 mammary analogue secretory carcinomas harbored the ETV6 translocation and were strongly mammaglobin positive. None of the 116 other tumors carried the ETV6 translocation; however, mammaglobin staining was present in 1 (100%) of 1 low-grade cribriform cystadenocarcinoma, 2 (67%) of 3 polymorphous low-grade adenocarcinomas, 2 (67%) of 3 salivary duct carcinomas, 2 (11%) of 18 mucoepidermoid carcinomas, and 2 (6%) of 33 pleomorphic adenomas. Mammaglobin is highly sensitive for mammary analogue secretory carcinoma, but immunostaining can occur in a variety of tumors that do not harbor the ETV6 translocation. Strategic use of mammaglobin immunostaining has a role in the differential diagnosis of salivary gland neoplasms, but it should not be indiscriminately used as a confirmatory test for mammary analogue secretory carcinoma.

  19. Cloning of Mammary Stem Cells

    DTIC Science & Technology

    2001-11-01

    these parity-induced cells do represent a totipotent mammary stem cell population per se, but these cells might support stem cell maintenance as... Stem Cells PRINCIPAL INVESTIGATOR: Dr. Kay-Uwe Wagner CONTRACTING ORGANIZATION: University of Nebraska Medical Center Omaha, Nebraska 68198-6810 REPORT...Mammary Stem Cells DAMD17-00-1-0641 6. AUTHOR(S) Dr. Kay-Uwe Wagner 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT

  20. Breed- and age-related differences in canine mammary tumors

    PubMed Central

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-01-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

  1. Breed- and age-related differences in canine mammary tumors.

    PubMed

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-04-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted.

  2. Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment

    PubMed Central

    2011-01-01

    Introduction The mammary primordium forms during embryogenesis as a result of inductive interactions between its constitutive tissues, the mesenchyme and epithelium, and represents the earliest evidence of commitment to the mammary lineage. Previous studies of embryonic mouse mammary epithelium indicated that, by mid-gestation, these cells are determined to a mammary cell fate and that a stem cell population has been delimited. Mammary mesenchyme can induce mammary development from simple epithelium even across species and classes, and can partially restore features of differentiated tissue to mouse mammary tumours in co-culture experiments. Despite these exciting properties, the molecular identity of embryonic mammary cells remains to be fully characterised. Methods Here, we define the transcriptome of the mammary primordium and the two distinct cellular compartments that comprise it, the mammary primordial bud epithelium and mammary mesenchyme. Pathway and network analysis was performed and comparisons of embryonic mammary gene expression profiles to those of both postnatal mouse and human mammary epithelial cell sub-populations and stroma were made. Results Several of the genes we have detected in our embryonic mammary cell signatures were previously shown to regulate mammary cell fate and development, but we also identified a large number of novel candidates. Additionally, we determined genes that were expressed by both embryonic and postnatal mammary cells, which represent candidate regulators of mammary cell fate, differentiation and progenitor cell function that could signal from mammary lineage inception during embryogenesis through postnatal development. Comparison of embryonic mammary cell signatures with those of human breast cells identified potential regulators of mammary progenitor cell functions conserved across species. Conclusions These results provide new insights into genetic regulatory mechanisms of mammary development, particularly

  3. Isolation of canine mammary cells with stem cell properties and tumour-initiating potential.

    PubMed

    Cocola, C; Anastasi, P; Astigiano, S; Piscitelli, E; Pelucchi, P; Vilardo, L; Bertoli, G; Beccaglia, M; Veronesi, M C; Sanzone, S; Barbieri, O; Reinbold, R A; Luvoni, G C; Zucchi, I

    2009-07-01

    Recent data suggest that mammary carcinogenesis may be driven by cancer stem cells (CSCs) derived from mutated adult stem cells, which have acquired aberrant cell self-renewal or by progenitor cells that have acquired the capacity for cell self-renewal. Spontaneous mammary cancers in cats and dogs are important models for the understanding of human breast cancer and may represent alternative species model systems that can significantly contribute to the study of human oncogenesis. With the goal of identifying markers for isolating human breast CSCs, we have generated a canine model system to isolate and characterize normal and CSCs from dog mammary gland. Insight into the hierarchical organization of canine tumours may contribute to the development of universal concepts in oncogenesis by CSCs. Cells with stem cell properties were isolated from normal and tumoural canine breast tissue and propagated as mammospheres and tumourspheres in long-term non-adherent culture conditions. We showed that cells obtained from spheres that display self-renewing properties, have multi-lineage differentiation potential, could generate complex branched tubular structures in vitro and form tumours in NOD/SCID mice. We analysed these cells for the expression of human stem and CSC markers and are currently investigating the tumour-initiating properties of these cells and the hierarchical organization of normal and neoplastic canine mammary tissue.

  4. 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.

  5. Occurrence of tumours metastatic to bones and multicentric tumours with skeletal involvement in dogs.

    PubMed

    Trost, M E; Inkelmann, M A; Galiza, G J N; Silva, T M; Kommers, G D

    2014-01-01

    The skeletons of 110 dogs with malignant tumours of different origins were examined by necropsy examination over a 3-year period to identify bone metastases. Twenty-one cases of metastatic or multicentric tumours with bone involvement were recorded. In general, more female dogs presented with bony metastases; however, when the dogs with mammary tumours were omitted, the gender distribution of the cases was approximately equivalent. The mammary gland was the primary site of most of the metastatic bone lesions, followed by the musculoskeletal system and the respiratory system. The majority (77%) of metastases were grossly visible and present in multiple bones. However, in 23% of the cases, the metastases could be diagnosed only at the microscopical level. The vertebrae and the humerus were the most frequently affected bones regardless of the primary site and the histogenesis of the tumours. The results of this study revealed a high prevalence of bone metastases and/or bone involvement in dogs with multicentric tumours.

  6. Mammary Cancer and Activation of Transposable Elements

    DTIC Science & Technology

    2014-09-01

    AD_________________ Award Number: W81XWH-11-1-0402 TITLE: Mammary Cancer and Activation...TYPE Annual 3. DATES COVERED 1 Sep 2013 – 31 Aug 2014 4. TITLE AND SUBTITLE Mammary Cancer and Activation of Transposable Elements 5a. CONTRACT...investigate molecular events occurring in the preclinical stages of mammary cancer. Specifically, the project investigates the intersection between the

  7. 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…

  8. FACS Sorting Mammary Stem Cells.

    PubMed

    Iriondo, Oihana; Rábano, Miriam; Vivanco, María D M

    2015-01-01

    Fluorescent-activated cell sorting (FACS) represents one of the key techniques that have been used to isolate and characterize stem cells, including cells from the mammary gland. A combination of approaches, including recognition of cell surface antigens and different cellular activities, has facilitated the identification of stem cells from the healthy mammary gland and from breast tumors. In this chapter we describe the protocol to use FACS to separate breast cancer stem cells, but most of the general principles discussed could be applied to sort other types of cells.

  9. 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.

  10. Pulmonary adenosquamous carcinoma in a dog.

    PubMed

    Sato, T; Ito, J; Shibuya, H; Asano, K; Watari, T

    2005-12-01

    A mass that developed in the lung of a 10-year-old mixed-breed dog was pathologically examined. Histopathological examination showed papillary and tubular growth of glandular epithelium-like cells in some areas and growth of squamous cells arranged in nests in other areas, showing coexistence of adenocarcinoma and squamous cell carcinoma in a lung tumour. Immunohistochemical staining with anti-keratin-cytokeratin antibody was strongly positive for cytoplasms in both components. Electron microscopically, the neoplastic cells of the adenocarcinoma component had features of glandular cells, with microvilli, numerous free ribosomes, large round secretory granules and intercellular desmosomes. Non-keratinized squamous cells had tonofilaments and intercellular desmosomes. These findings led to the diagnosis of primary adenosquamous carcinoma, which demonstrates phenotypic profiles characteristic of both epidermal keratinocytes and glandular epithelium.

  11. Defect in ND2, COX2, ATP6 and COX3 mitochondrial genes as a risk factor for canine mammary tumour.

    PubMed

    Surdyka, M; Slaska, B

    2016-06-09

    The aim of this study was to identify mutations in ND2, COX2, ATP6 and COX3 mitochondrial genes in canine mammary tumour, determine their association with the process of neoplastic transformation, and phenotypic traits of dogs. In total, 93 biological samples, including blood, normal and neoplastic tissue samples from 31 dogs with diagnosed malignant canine mammary tumours were analysed. DNA sequencing of genes as well as bioinformatics and statistical analyses were performed. A total of 28 polymorphic loci and 11 mutations were identified. One of the mutations was blood heteroplasmy and two of the mutations caused an amino acid change in p.N117S and p.A184T. For the first time, mutations in mitochondrial genes were detected in dogs with mammary tumours. A statistically significant association between the presence of mutations and the size and age of dogs was demonstrated. Some of these changes may imply that these are the hotspot mutations of canine mammary tumour.

  12. Dog Bite Emergencies

    MedlinePlus

    ... Emergency Care Animal Welfare Veterinary Careers Public Health Dog bite emergencies What do I do if I’ ... vaccination records. What do I do if my dog bites someone? Dog bites are scary for everyone ...

  13. Squamous cell carcinoma of the anal sac in five dogs.

    PubMed

    Esplin, D G; Wilson, S R; Hullinger, G A

    2003-05-01

    Tumors of the perianal area of dogs are common and include multiple tumor types. Whereas perianal adenomas occur often, adenocarcinomas of the apocrine glands of the anal sac occur less frequently. A review of the literature revealed no reports of squamous cell carcinomas arising from the epithelial lining of the anal sac. Squamous cell carcinomas originating from the lining of the anal sac were diagnosed in five dogs. Microscopically, the tumors consisted of variably sized invasive nests and cords of epithelial cells displaying squamous differentiation. Four of the five dogs were euthanatized because of problems associated with local infiltration by the tumors. In the fifth dog, there was no evidence of tumor 7 months after surgical removal, but further follow up was not available.

  14. Mammaglobin and S-100 immunoreactivity in salivary gland carcinomas other than mammary analogue secretory carcinoma.

    PubMed

    Patel, Kalyani R; Solomon, Isaac H; El-Mofty, Samir K; Lewis, James S; Chernock, Rebecca D

    2013-11-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that has morphologic features similar to secretory carcinoma of the breast and that also harbors the same ETV6 translocation. Diffuse mammaglobin and S-100 immunoreactivity are used to differentiate MASC from its morphologic mimics, especially acinic cell carcinoma and adenocarcinoma, not otherwise specified. However, the combination of mammaglobin and S-100 immunoreactivity has not been well studied in other types of salivary gland carcinomas that may have focal areas reminiscent of MASC. Here we evaluated mammaglobin and S-100 immunoreactivity in 15 cases each of polymorphous low-grade adenocarcinoma, adenoid cystic carcinoma and mucoepidermoid carcinoma, and also in 2 cases of adenocarcinoma, not otherwise specified, and 1 mucinous adenocarcinoma. Cases with significant co-expression of mammaglobin and S-100 (moderate or strong immunoreactivity in >25% of tumor cells) were further analyzed by fluorescence in situ hybridization using the ETV6 (12p13) break-apart probe. Nine cases (60%) of polymorphous low-grade adenocarcinoma and two (13.3%) of adenoid cystic carcinoma met the criteria for significant co-expression of mammaglobin and S-100. All were negative for the ETV6 translocation by fluorescence in situ hybridization. Although mammaglobin and S-100 positivity was seen in the majority of polymorphous low-grade adenocarcinomas and a minority of adenoid cystic carcinomas, none were positive for the ETV6 translocation characteristic of MASC. This indicates a need for caution in the use of immunohistochemistry for diagnosing MASC, especially in the absence of cytogenetic confirmation.

  15. 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

  16. Selecting shelter dogs for service dog training.

    PubMed

    Weiss, Emily

    2002-01-01

    Service dogs are an essential aid to persons with disabilities, providing independence, mobility, and improved self-esteem. Because of these proven benefits, the growing se of service dogs is creating a demand and supply crisis. One major cause is the 50% verage dropout rate for dogs selected for training. Weiss and Greenber (1997) re-cently found that a dog, successful on the most commonly used selection test items, was as likely to be either a poor or a good candidate for service work. The experiment presented here evaluated test items developed by the author in 15 years of experience with dogs. The test items were administered to 75 dogs from the Kansas Humane So-ciety. Once tested, the dogs received obedience and retrieval training. The experiment assessed each dog on behavior over 5 weeks of training versus performance on each selection test item. A subset of the selection items, combined in a regression analysis, accounted for 36.4% of the variance with R = 0.603. This research also revealed a reli-able test for dog aggression without risking injury to dog or tester. Items for testing in-cluded fear, motivation, and submission. Another set of selection items reliably pre-dicted the trait of "high energy" commonly described as "high strung." Future research should involve investigating the effectiveness of both cortisol levels and blood pressure in predicting traits to help strengthen the predictive value of the tool and then testing on dogs trained to be full service dogs.

  17. [Endoscopic diagnosis of Barrett's adenocarcinoma].

    PubMed

    Yoshio, H; Takashi, Y; Mitsuyo, H; Nobuhiko, Y; Tatsurou, T; Kazuhiko, S; Yoko, H; Shigemasa, I; Hisanaga, M; Osamu, H; Katsuyoshi, S; Seishi, U; Matsushita, H; Masahiko, T

    1999-03-01

    Biopsy specimens can reveal that esophageal cancer is an adenocarcinoma but they cannot show that its origin is Barrett's mucosa. Therefore we must show during endoscopy that the tumor exists in Barrett's mucosa. We reported that Barrett's esophagus could be clearly diagnosed at endoscopy as the columnar mucosa lying on the longitudinal vessels in the lower esophagus. We define Barrett's esophagus as "the columnar mucosa in the esophagus which exists continuously more than 2 cm in circumference from the stomach." Short-segment Barrett's esophagus (SSBE) is "the columnar mucosa which exists in the esophagus continuously from the stomach but its length has a part under 2 cm in length." Endoscopically Barrett's adenocarcinoma is visualized as a lesion with a reddish and uneven mucosal surface. Barrett's adenocarcinomas occur in the SSBE as well. Endoscopic observation at periodic intervals is necessary not only for cases with Barrett's esophagus but also with SSBE. A further examination is necessary to determine the application of EMR for superficial Barrett's adenocarcinoma.

  18. 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.

  19. Validation of a low-cost modified technique for constructing tissue microarrays for canine mammary tumor analysis.

    PubMed

    Silva, Franciele Basso Fernandes; Leite, Juliana da Silva; de Mello, Marcela Freire Vallim; Ferreira, Ana Maria Reis

    2016-09-01

    Compared with conventional histological paraffin blocks, tissue microarray (TMA) represents a "high-throughput tool" that provides rapid results, a time- and cost-effective approach and simultaneous investigation of several tissue samples under the same conditions. Given the large number of cases of dogs affected with mammary tumors, the complexity of these tumors and their similarity with breast cancer in women, this study aimed to validate a low-cost modified method to construct TMAs for canine mammary tumor analysis using immunomarkers. Carcinoma cases were selected from canine mammary carcinomas in mixed tumors (CMT) because this tumor type is the most heterogeneous among the histopathological types of mammary tumors observed in female dogs. Through a histopathological examination, tumor representativity was compared between conventional sections and histological sections obtained from the TMA block; both were stained with hematoxylin and eosin. An immunohistochemistry analysis was performed to compare the percentages of immunoreactive cells obtained in whole tissue sections versus those obtained from sections from the TMA block. Streptavidin-biotin peroxidase complex and anti-PCNA, anti-vimentin and anti-pancytokeratin antibodies were used. Statistical analysis consisted of the nonparametric Friedman's test (p≤0.05) and descriptive statistical analysis. Histopathological analysis showed tumor representativity in all TMA cores selected for the study. There was no difference between the immunohistochemical analysis of mammary tumors using conventional histological sections or sections obtained from a single 1-mm-diameter TMA core, regardless of the marker used: PCNA (p=0.279), pancytokeratin (p=0.243) and vimentin (p=0.967). The results did not change even when the means of any number of cores were compared among each other and with the conventional histological section: PCNA (p=0.413), pancytokeratin (p=0.177) and vimentin (p=1.0). Therefore, this study

  20. Esophageal and gastric cancers with metastases induced in dogs by N-ethyl-N'-nitro-N-nitrosoguanidine.

    PubMed

    Sasajima, K; Kawachi, T; Sano, T; Sugimura, T; Shimosato, Y

    1977-06-01

    Three 6-month-old male beagle dogs were given a solution of 150 microng N-ethyl-N'-nitrosoguanidine (ENNG)/ml to drink ad libitum for 9 months. They all developed esophageal squamous cell carcinomas and gastric adenocarcinomas. The stomach adenocarcinomas were mostly in the antrum along the lesser curvature and were either well differentiated or poorly differentiated, with or without signet ring cells. The well-differentiated adenocarcinomas metastasized to the liver, and the poorly differentiated ones metastasized to the lymph nodes. The gastric mucosa in the antrum was atrophic, and the muscularis mucosae was fibrotic. Esophageal lesions were multicentric moderately differentiated squamous cell carcinomas, and they developed without diffuse hyperplastic changes of the epithelium. One dog with a large ulcerated carcinoma of the esophagus had metastases in the lung, liver, peritoneum, and abdominal lymph nodes. One dog also had a hemangiosarcoma with hepatic metastasis and spindle cell sarcoma in the stomach and duodenum, respectively.

  1. Prevention of Human Mammary Carcinogenesis.

    DTIC Science & Technology

    1996-07-01

    of HER-2/neu oncogene-transformed human mammary epithelial cells by a green tea polyphenol. Breast Cancer Res Treat 38:100; 1996 8. Telang NT, Katdare...apoptosis and anchorage-dependent colony forming efficiency. Appendix Figure 5 (AF-5): Effect of (-) epigallo catechin gallate (EGCG) on 184- B5/HER cells is... tea polyphenol. Ann. NY Acad. Sci. 768: 215- 222, 1995. Appendix Pubilcation 5 (AP-5): Fishman J, Osborne MP, Telang NT. The role of estrogen in

  2. Detection of autoantibodies against survivin in sera from cancer dogs.

    PubMed

    Tango, Yumiko; Kano, Rui; Maruyama, Haruhiko; Asano, Kazushi; Tanaka, Shigeo; Hasegawa, Astuhiko; Kamata, Hiroshi

    2010-07-01

    Survivin overexpression has been reported in relation to tumor malignancy, suggesting that it is an unfavorable prognostic marker, and antibody responses to this protein have been confirmed in human cancer patients. In this study, we investigated antibody responses to survivin in canine cancer cases, and examined the prevalence of such responses by enzyme-linked immunosorbent assay (ELISA) using recombinant canine survivin protein as the antigen. The cut-off value for positivity in the anti-survivin ELISA was 0.35, as determined using the mean absorbance +2 S.D. of samples from healthy dogs. Sera from 16 of 59 (27.1%) cancer and 3 of 25 (12%) non-cancer disease dogs were positive on ELISA. The highest positivity rates (>50%) among the cancer cases were seen in dogs with mammary tumor, squamous cell carcinoma and melanoma.

  3. Somatic SNPs of the BRCA2 gene at the fragments encoding RAD51 binding sites of canine mammary tumors.

    PubMed

    Ozmen, O; Kul, S; Risvanli, A; Ozalp, G; Sabuncu, A; Kul, O

    2017-01-30

    Mammary tumors are the most common tumor type both in women and in female dogs. In women, heritable breast cancers have been linked mutations in the breast cancer susceptibility gene BRCA2 and it contains eight BRC repeats in exon 11 that bind to RAD51. In this study, we investigated the sequence variations of BRC1-BRC8 and C-terminus of canine BRCA2 gene. From a total of 64 canine patients with mammary tumors, 31 mammary tumors with benign and malign carcinomas and the 3 normal mammary glands were used for the study. In this study, 19 SNPs of exon 11 of BRCA2 in canine mammary tumors were detected for the first time. The c.2383A>C (T1425P) SNP was found to be the most probable disease-associated nsSNP. Our findings suggest that T1425P variation in BRC3 to be the most probable disease-associated nsSNP and may affect RAD51 binding strength.

  4. Canine Mammary Cancer Stem Cells are Radio- and Chemo- Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype.

    PubMed

    Pang, Lisa Y; Cervantes-Arias, Alejandro; Else, Rod W; Argyle, David J

    2011-03-30

    Canine mammary carcinoma is the most common cancer among female dogs and is often fatal due to the development of distant metastases. In humans, solid tumors are made up of heterogeneous cell populations, which perform different roles in the tumor economy. A small subset of tumor cells can hold or acquire stem cell characteristics, enabling them to drive tumor growth, recurrence and metastasis. In veterinary medicine, the molecular drivers of canine mammary carcinoma are as yet undefined. Here we report that putative cancer stem cells (CSCs) can be isolated form a canine mammary carcinoma cell line, REM134. We show that these cells have an increased ability to form tumorspheres, a characteristic of stem cells, and that they express embryonic stem cell markers associated with pluripotency. Moreover, canine CSCs are relatively resistant to the cytotoxic effects of common chemotherapeutic drugs and ionizing radiation, indicating that failure of clinical therapy to eradicate canine mammary cancer may be due to the survival of CSCs. The epithelial to mesenchymal transition (EMT) has been associated with cancer invasion, metastasis, and the acquisition of stem cell characteristics. Our results show that canine CSCs predominantly express mesenchymal markers and are more invasive than parental cells, indicating that these cells have a mesenchymal phenotype. Furthermore, we show that canine mammary cancer cells can be induced to undergo EMT by TGFβ and that these cells have an increased ability to form tumorspheres. Our findings indicate that EMT induction can enrich for cells with CSC properties, and provide further insight into canine CSC biology.

  5. 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.

  6. Hepatoid Adenocarcinoma of the Urachus

    PubMed Central

    Jimenez, Carlos Andrés; Carrascal, Edwin

    2016-01-01

    Hepatoid adenocarcinoma of the urachus is a rare condition. We present the case of a 51-year-old female who developed abdominal pain and hematuria. Pelvic magnetic resonance imaging (MRI) reported an urachal mass with invasion to the bladder that was resected by partial cystectomy. On light microscopy the tumor resembled liver architecture, with polygonal atypical cells in nest formation and trabecular structures. Immunochemistry was positive for alfa-fetoprotein (AFP) and serum AFP was elevated. Hepatoid adenocarcinomas have been reported in multiple organs, being most commonly found in the stomach and the ovaries. Bladder compromise has been rarely described in the literature, and it has been associated with poor prognosis, low remission rates, and early metastasis. PMID:27803830

  7. Oncocytic Adenocarcinoma of the Orbit.

    PubMed

    Harris, Gerald J; Paul, Sean; Hunt, Bryan C

    Oncocytic adenocarcinoma of the orbit is a rare tumor, with 1 case of nonlacrimal sac, nonlacrimal gland origin, and a poor outcome previously reported. An 85-year-old man with a 2-month history of left-sided epiphora, enlarging eyelid nodules, and diplopia in left gaze was found on imaging to have a poorly circumscribed, nodular mass of uniform radiodensity in the inferomedial orbit. Incisional biopsy revealed morphologic and immunohistochemical features of oncocytic adenocarcinoma with origin in the caruncle suspected, and CT of the neck, chest, abdomen, and pelvis showed no metastases or remote primary tumor source. Based on multidisciplinary consensus, orbital exenteration with adjuvant radiation therapy was performed, and there was no evidence of residual or recurrent tumor 2 years after treatment.

  8. 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

  9. Spontaneous infarcted adenoma of the mammary gland in a Wistar Hannover GALAS rat

    PubMed Central

    Matsushita, Kohei; Toyoda, Takeshi; Inoue, Kaoru; Morikawa, Tomomi; Sone, Mizuki; Ogawa, Kumiko

    2016-01-01

    Spontaneous massive infarction of mammary gland tumors has been reported to occur infrequently in humans. A subcutaneous mass (18 × 17 × 10 mm) was observed in the right axilla extending to the chest region of a 110-week-old female Wistar Hannover GALAS rat. Histopathologically, a well-circumscribed mass with lobular structures was present in the subcutis. Most of the mass was occupied by extensive coagulative necrosis of neoplastic cells with relatively uniform acinar and ductal structures. Although each necrotic acinar structure was separated by reticular fibers, periacinar stromal collagen fibers were not abundant. Considering the site of occurrence and histological features, the necrotic tissue was diagnosed as adenoma of the mammary gland. The necrotic region lacked hemorrhage and obvious inflammatory cell infiltration, indicating the necrosis was caused by infarction. Although multiple necrosis and focal infarction are occasionally observed in large-sized tumors in rodents, especially in adenocarcinomas, the present case was characteristic, with the massive infarction involving most parts of the tumor despite the relatively small size and low atypia of neoplastic cells. This is a rare case of spontaneous infarcted adenoma of the mammary gland in rats histologically resembling human cases. PMID:28190925

  10. Optimal lymphadenectomy for esophageal adenocarcinoma.

    PubMed

    Oezcelik, A

    2013-08-01

    Recently published data have shown that an extended lymphadenectomy during the en bloc esophagectomy leads to a significant increased long-term survival for esophageal adenocarcinoma. On the other hand some studies indicate that the increased survival is based on stage migration and that the surgical complication rate is increased after extended lymphadenectomy. The aim of this review was to give an overview about all aspects of an extended lymphadenectomy in patients with esophageal adenocarcinoma. The review of the literature shows clearly that the number of involved lymph nodes is an independent prognostic factor in patients with esophageal adenocarcinoma. Furthermore, an extended lymphadenectomy leads to an increased long-term survival. Some studies describe that 23 lymph nodes should be removed to predict survival; other studies 18 lymph nodes or 15 lymph nodes. Opponents indicate that the survival benefit is based on stage migration. The studies with a large study population have performed a Cox regression analyzes and identified the number of lymph nodes removed as an independent factor for improved survival, which means it is significant independently from other parameters. Under these circumstances is stage migration not an option to explain the survival benefit. An important difficulty is, that there is no standardized definition of an extended lymphadenectomy, which means the localization and number of removed lymph nodes differ depending from the performing centre. The controversies regarding the survival benefit of the lymphadenectomy is based on the lack of standardisation of the lymphadenectomy. The main goal of further studies should be to generate a clear definition of an extended lymphadenectomy in patients with esophageal adenocarcinoma.

  11. Multiple susceptibility loci for radiation-induced mammary tumorigenesis in F2[Dahl S x R]-intercross rats.

    PubMed

    Herrera, Victoria L; Ponce, Lorenz R; Ruiz-Opazo, Nelson

    2013-01-01

    Although two major breast cancer susceptibility genes, BRCA1 and BRCA2, have been identified accounting for 20% of breast cancer genetic risk, identification of other susceptibility genes accounting for 80% risk remains a challenge due to the complex, multi-factorial nature of breast cancer. Complexity derives from multiple genetic determinants, permutations of gene-environment interactions, along with presumptive low-penetrance of breast cancer predisposing genes, and genetic heterogeneity of human populations. As with other complex diseases, dissection of genetic determinants in animal models provides key insight since genetic heterogeneity and environmental factors can be experimentally controlled, thus facilitating the detection of quantitative trait loci (QTL). We therefore, performed the first genome-wide scan for loci contributing to radiation-induced mammary tumorigenesis in female F2-(Dahl S x R)-intercross rats. Tumorigenesis was measured as tumor burden index (TBI) after induction of rat mammary tumors at forty days of age via ¹²⁷Cs-radiation. We observed a spectrum of tumor latency, size-progression, and pathology from poorly differentiated ductal adenocarcinoma to fibroadenoma, indicating major effects of gene-environment interactions. We identified two mammary tumorigenesis susceptibility quantitative trait loci (Mts-QTLs) with significant linkage: Mts-1 on chromosome-9 (LOD-2.98) and Mts-2 on chromosome-1 (LOD-2.61), as well as two Mts-QTLs with suggestive linkage: Mts-3 on chromosome-5 (LOD-1.93) and Mts-4 on chromosome-18 (LOD-1.54). Interestingly, Chr9-Mts-1, Chr5-Mts-3 and Chr18-Mts-4 QTLs are unique to irradiation-induced mammary tumorigenesis, while Chr1-Mts-2 QTL overlaps with a mammary cancer susceptibility QTL (Mcs 3) reported for 7,12-dimethylbenz-[α]antracene (DMBA)-induced mammary tumorigenesis in F2[COP x Wistar-Furth]-intercross rats. Altogether, our results suggest at least three distinct susceptibility QTLs for irradiation

  12. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Inspection of mammary glands. 310.17... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.17 Inspection of mammary glands. (a) Lactating mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed...

  13. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Inspection of mammary glands. 310.17... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.17 Inspection of mammary glands. (a) Lactating mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed...

  14. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Inspection of mammary glands. 310.17... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.17 Inspection of mammary glands. (a) Lactating mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed...

  15. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Inspection of mammary glands. 310.17... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.17 Inspection of mammary glands. (a) Lactating mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed...

  16. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Inspection of mammary glands. 310.17... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.17 Inspection of mammary glands. (a) Lactating mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed...

  17. Serological proteome analysis of dogs with breast cancer unveils common serum biomarkers with human counterparts.

    PubMed

    Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi; Rahbarghazi, Reza

    2014-03-01

    Canine mammary tumor is being touted as a model for investigating the human breast cancer. Breast cancer of the both species has similar biological behavior, histopathologic characteristics, and metastatic pattern. In this study, we used the serological proteome analysis to detect autoantigens that elicit a humoral response in dogs with mammary tumor in order to identify serum biomarkers with potential usefulness as diagnostic markers and to better understand molecular mechanisms underlying canine breast cancer development. Protein extract from a cell line was subject to 2DE followed by Western blotting using sera from 15 dogs with mammary tumor and sera from 15 healthy control dogs. Immunoreactive autoantigens were subsequently identified by the MALDI-TOF MS. Four autoantigens, including manganese-superoxide dismutase, triose phosphate isomerase, alpha-enolase, and phosphoglycerate mutase1, with significantly higher immunoreactivity in the tumor samples than in the normal samples were identified as biomarker candidates. Immunohistochemistry and Western blotting revealed higher expression of these biomarkers in the malignant tumors than in the normal or benign tumors. The autoantigens found in this study have been reported to elicit autoantibody response in the human breast cancer, indicating the similarity of breast cancer proteome profile in dogs with that in human beings.

  18. Cardiopulmonary resuscitation with vasopressin in a dog.

    PubMed

    Schmittinger, Christian A; Astner, Sandra; Astner, Leonhard; Kössler, Josef; Wenzel, Volker

    2005-03-01

    That endogenous vasopressin levels in successfully resuscitated human patients were significantly higher than in patients who died pointed to the possible benefit of administering vasopressin during cardiopulmonary resuscitation (CPR). Several CPR studies in pigs showed that vasopressin improved blood flow to vital organs, cerebral oxygen delivery, resuscitability and neurological outcome when compared with epinephrine. In a small clinical study, vasopressin significantly improved short-term survival when compared with epinephrine indicating its potential as an alternative pressor to epinephrine during CPR in human beings. As there was little clinical data available at that time, its recommended use was limited to adult human beings with shock-refractory ventricular fibrillation. In this report, we present the case of a dog in which the successful management of intraoperative asystolic cardiac arrest involved vasopressin. Unexpected cardiac arrest occurred during anaesthesia for the surgical removal of multiple mammary adenocarcinomata in a 11-year-old Yorkshire terrier. Despite an ASA physical status assignation of III, the dog was successfully resuscitated with external chest compressions, intermittent positive pressure ventilation and vasopressin (2 doses of 0.8 IU kg(-1)) and was discharged 3 days later without signs of neurological injury. We believe vasopressin contributed to restoring spontaneous circulation. It may prove increasingly useful in perioperative resuscitation in dogs.

  19. Transplantation of a mammary stromal cell line into a mammary fat pad: development of the site-specific in vivo analysis system for mammary stromal cells.

    PubMed

    Nakatani, Hajime; Aoki, Naohito; Nadano, Daita; Matsuda, Tsukasa

    2011-01-01

    The interaction between mammary epithelial and stromal tissue is considered to be important in breast tissue development. In this study, we developed a transplantation procedure for the mammary stromal fibroblastic cell line (MSF) to examine its life in vivo. First we established MSF cells which stably expressed lacZ (lacZ/MSF) and had characteristics of mammary stromal cells. The lacZ/MSF cells were then transplanted into a cleared mammary fat pad of syngenic mice with and without mammary primary epithelial organoids. Whole mount X-gal and carmine staining of the transplants revealed that a number of undifferentiated lacZ/MSF cells survived around the mammary epithelial tissue when transplanted with organoids. These results indicate that transplantation of MSF cells into mammary fat pad was accomplished by co-transplantation with primary mammary organoids. Finally, we discuss the application of transplantation procedure for in vivo studies of the mammary stromal tissue development and stromal-epithelial interactions.

  20. Metastatic adenocarcinoma of unknown primary origin.

    PubMed

    Hammar, S P

    1998-12-01

    Adenocarcinomas account for up to 60% of all metastatic neoplasms of unknown primary origin. In general, adenocarcinomas are the most difficult metastatic tumor to accurately identify the primary site. Some metastatic adenocarcinomas have distinctive histological features that allow for their site determination (eg, colonic adenocarcinoma, bronchioloalveolar cell carcinoma), although the majority of metastatic adenocarcinomas have histological features that are not distinctive enough to allow for a specific diagnosis of their origin. For this reason, electron microscopy and immunohistochemistry have been used to help identify the exact type (origin) of metastatic adenocarcinomas. Relatively specific ultrastructural features used to diagnose metastatic adenocarcinomas of unknown primary origin include tubular myelin, intranuclear surfactant apoprotein tubular inclusions, Clara cell granules, uniform short microvilli with filamentous cores and core rootlets, Langerhans cells associated with neoplastic cells, cytoplasmic hyaline globules, lipid droplets, glycogen, and cytoplasmic crystals. Only a few of these ultrastructural features are absolutely specific. Relatively specific immunohistochemical tests used to diagnose metastatic adenocarcinomas of unknown primary origin include prostate-specific antigen, thyroglobulin, estrogen and progesterone receptor proteins, thyroid transcription factor-I, and surfactant apoproteins. Of these, prostate-specific antigen and thyroglobulin are the most specific. The purpose of this article is to discuss the use of electron microscopy and immunohistochemistry in the site-specific diagnosis of metastatic adenocarcinomas of unknown primary origin.

  1. Mammary Malignancy in The Male

    PubMed Central

    Alexander, Leslie L.; Benninghoff, David L.; Camiel, Mortimer R.; Medina, Antonio

    1978-01-01

    Mammary carcinoma in the male, a relatively uncommon disease, represents about 0.9 to 1.5 percent of all breast cancers. 1,2 The authors reviewed 16 cases of male breast cancer seen in a 30-year period at the State University of New York, Kings County Hospital Medical Center in Brooklyn, and the North Shore University Hospital in Manhasset. Epidemiology, etiology, demography, signs and symptoms, management, and prognosis are discussed. A review of pertinent literature is presented. ImagesFigure 1Figure 2 PMID:722829

  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. Tumors and tumor-like lesions in the mammary gland of 24 pet rabbits: a histomorphological and immunohistochemical characterization.

    PubMed

    Schöniger, S; Horn, L-C; Schoon, H-A

    2014-05-01

    The aim of this retrospective study (2004-2011) was to examine mammary tumors and tumor-like lesions in 24 pet rabbits by histopathology and immunohistochemistry. Rabbits were aged 2 to 8 years. Seventeen were female and 7 female-spayed. Diagnosed tumor-like lesions were lobular hyperplasia (2 rabbits) and multiple cysts (10 rabbits). Tumors included cystadenoma (7 tumors; 3 rabbits), intraductal papilloma (2 tumors; 1 rabbit), intraductal papillary carcinoma (1 tumor), adenocarcinoma (14 tumors; 13 rabbits), adenosquamous carcinoma (2 tumors; 2 rabbits), and matrix-producing carcinoma (1 tumor). The most frequently diagnosed lesion was invasive carcinoma (n = 17). Ten rabbits had several lesions. Immunohistochemistry for calponin and p63 showed that the diagnosed tumor-like lesions, benign tumors, and noninvasive carcinoma had a peripheral myoepithelial layer that was lacking in the invasive carcinomas. In 13 of 14 (93%) of the invasive carcinomas, however, there were variable numbers of calponin- and/or p63-immunopositive cells ranging from 0.1% to 40% with morphological features of either retained nonneoplastic myoepithelial cells or neoplastic epithelial cells with a myoepithelial differentiation. Tumor recurrence was reported in the rabbit with the matrix-producing carcinoma and in 3 rabbits with mammary adenocarcinomas displaying ≥20 mitotic figures in 10 high-power fields and high numbers of neoplastic cells with a myoepithelial differentiation (19%-39%). The rabbit with the matrix-producing mammary carcinoma developed cutaneous metastases confirmed by histopathology. This study shows that different types of mammary tumor-like lesions and tumors can occur in pet rabbits.

  4. Dog Bite Prevention

    MedlinePlus

    ... records. Consult with your veterinarian about your dog’s aggressive action. Your veterinarian can examine your dog to ... or one they know. Some owners actually promote aggression in their dogs or allow aggression to go ...

  5. 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.

  6. Transcriptomic Microenvironment of Lung Adenocarcinoma.

    PubMed

    Bossé, Yohan; Sazonova, Olga; Gaudreault, Nathalie; Bastien, Nathalie; Conti, Massimo; Pagé, Sylvain; Trahan, Sylvain; Couture, Christian; Joubert, Philippe

    2017-03-01

    Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.

  7. Proteomic Analysis of Genistein Mammary Cancer

    DTIC Science & Technology

    2005-07-01

    pathways we found up-regulated P-ERK-1, but no significant short-term changes in the tyrosine hydroxylase and iNOS protein expressions in mammary glands...of 21 day old rats. At day 50, there was significant up-regulation of tyrosine hydroxylase and VEGF-R2. This and previous work suggests that early...mammary glands of 21 day old rats only. In 50 day old rats, mammary tyrosine hydroxylase protein expression was up- regulated and now we report that

  8. 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.

  9. Uterine adenocarcinoma with feline leukemia virus infection.

    PubMed

    Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa; Kim, Okjin

    2011-12-01

    Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection.

  10. Pathologic progression of mammary carcinomas in a C3(1)/SV40 T/t-antigen transgenic rat model of human triple-negative and Her2-positive breast cancer.

    PubMed

    Hoenerhoff, M J; Shibata, M A; Bode, A; Green, J E

    2011-04-01

    The C3(1) component of the rat prostate steroid binding protein has been used to target expression of the SV40 T/t-antigen to the mammary epithelium of mice resulting in pre-neoplastic lesions that progress to invasive and metastatic cancer with molecular features of human basal-type breast cancer. However, there are major differences in the histologic architecture of the stromal and epithelial elements between the mouse and human mammary glands. The rat mammary gland is more enriched with epithelial and stromal components than the mouse and more closely resembles the cellular composition of the human gland. Additionally, existing rat models of mammary cancer are typically estrogen receptor positive and hormone responsive, unlike most genetically engineered mouse mammary cancer models. In an attempt to develop a mammary cancer model that might more closely resemble the pathology of human breast cancer, we generated a novel C3(1)/SV40 T/t-antigen transgenic rat model that developed progressive mammary lesions leading to highly invasive adenocarcinomas. However, aggressive tumor development prevented the establishment of transgenic lines. Characterization of the tumors revealed that they were primarily estrogen receptor and progesterone receptor negative, and either her2/neu positive or negative, resembling human triple-negative or Her2 positive breast cancer. Tumors expressed the basal marker K14, as well as the luminal marker K18, and were negative for smooth muscle actin. The triple negative phenotype has not been previously reported in a rat mammary cancer model. Further development of a C3(1)SV40 T/t-antigen based model could establish valuable transgenic rat lines that develop basal-type mammary tumors.

  11. 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.

  12. Dogs catch human yawns.

    PubMed

    Joly-Mascheroni, Ramiro M; Senju, Atsushi; Shepherd, Alex J

    2008-10-23

    This study is the first to demonstrate that human yawns are possibly contagious to domestic dogs (Canis familiaris). Twenty-nine dogs observed a human yawning or making control mouth movements. Twenty-one dogs yawned when they observed a human yawning, but control mouth movements did not elicit yawning from any of them. The presence of contagious yawning in dogs suggests that this phenomenon is not specific to primate species and may indicate that dogs possess the capacity for a rudimentary form of empathy. Since yawning is known to modulate the levels of arousal, yawn contagion may help coordinate dog-human interaction and communication. Understanding the mechanism as well as the function of contagious yawning between humans and dogs requires more detailed investigation.

  13. Trace element transport in the mammary gland.

    PubMed

    Lönnerdal, Bo

    2007-01-01

    The mammary gland has a remarkable capacity to adapt to maternal deficiency or excess of iron, copper, and zinc and to homeostatically control milk concentrations of these essential nutrients. Similarly, it can regulate changes in concentrations of iron, copper, and zinc change during lactation. For iron, this regulation is achieved by transferrin receptor, DMT1, and ferroportin, whereas mammary gland copper metabolism is regulated by Ctr1, ATP7A, and ATP7B. Zinc homeostasis is complex, involving both zinc importers (Zip3) and zinc exporters (ZnT-1, ZnT-2, and ZnT-4). Both transcriptional and post-translational regulation can affect protein abundance and cellular localization of these transporters, finely orchestrating uptake, intracellular trafficking, and secretion of iron, copper, and zinc. The control of mammary gland uptake and milk secretion of iron, copper, and zinc protects both the mammary gland and the breast-fed infant against deficiency and excess of these nutrients.

  14. Mammary gland: From embryogenesis to adult life.

    PubMed

    Musumeci, Giuseppe; Castrogiovanni, Paola; Szychlinska, Marta Anna; Aiello, Flavia Concetta; Vecchio, Giada Maria; Salvatorelli, Lucia; Magro, Gaetano; Imbesi, Rosa

    2015-01-01

    The aim of this review is to focus on the molecular factors that ensure the optimal development and maintenance of the mammary gland thanks to their integration and coordination. The development of the mammary gland is supported, not only by endocrine signals, but also by regulatory molecules, which are able to integrate signals from the surrounding microenvironment. A major role is certainly played by homeotic genes, but their incorrect expression during the spatiotemporal regulation of proliferative, functional and differentiation cycles of the mammary gland, may result in the onset of neoplastic processes. Attention is directed also to the endocrine aspects and sexual dimorphism of mammary gland development, as well as the role played by ovarian steroids and their receptors in adult life.

  15. 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.

  16. The mammary cellular hierarchy and breast cancer.

    PubMed

    Oakes, Samantha R; Gallego-Ortega, David; Ormandy, Christopher J

    2014-11-01

    Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer.

  17. Expression of the aryl hydrocarbon receptor pathway and cyclooxygenase-2 in dog tumors.

    PubMed

    Giantin, M; Vascellari, M; Lopparelli, R M; Ariani, P; Vercelli, A; Morello, E M; Cristofori, P; Granato, A; Buracco, P; Mutinelli, F; Dacasto, M

    2013-02-01

    In humans, the aryl hydrocarbon receptor (AHR) gene battery constitutes a set of contaminant-responsive genes, which have been recently shown to be involved in the regulation of several patho-physiological conditions, including tumorigenesis. As the domestic dog represents a valuable animal model in comparative oncology, mRNA levels of cytochromes P450 1A1, 1A2 and 1B1 (CYP1A1, 1A2 and 1B1), AHR, AHR nuclear translocator (ARNT), AHR repressor (AHRR, whose partial sequence was here obtained) and cyclooxygenase-2 (COX2) were measured in dog control tissues (liver, skin, mammary gland and bone), in 47 mast cell tumors (MCTs), 32 mammary tumors (MTs), 5 osteosarcoma (OSA) and related surgical margins. Target genes were constitutively expressed in the dog, confirming the available human data. Furthermore, their pattern of expression in tumor biopsies was comparable to that already described in a variety of human cancers; in particular, both AHR and COX2 genes were up-regulated and positively correlated, while CYP1A1 and CYP1A2 mRNAs were generally poorly expressed. This work demonstrated for the first time that target mRNAs are expressed in neoplastic tissues of dogs, thereby increasing the knowledge about dog cancer biology and confirming this species as an useful animal model for comparative studies on human oncology.

  18. Spontaneous acromegaly: a retrospective case control study in German shepherd dogs.

    PubMed

    Fracassi, F; Zagnoli, L; Rosenberg, D; Furlanello, T; Caldin, M

    2014-10-01

    Acromegaly results from the overproduction of growth hormone in adulthood and is characterised by overgrowth of soft tissue and/or bone as well as insulin resistance. There are few data indicating the risk factors associated with this disease in dogs or its clinicopathological features and sequelae. The objective of this retrospective study was to catalogue and assess these aspects of the disease in German shepherd dogs (GSDs) which were found to be over-represented among acromegalic dogs attending two veterinary referral clinics over a period of 7 years. Each acromegalic dog (AD) was compared with two breed/age/sex matched controls. Clinical signs of acromegaly included panting, polyuria/polydipsia, widened interdental spaces, weakness, inspiratory stridor, macroglossia, weight gain, redundant skin folds, thick coat, exophthalmos and mammary masses. Serum alkaline phosphatase, creatine-kinase, glucose, triglyceride, phosphate ion, and 'calcium per phosphate product' concentrations were significantly higher in acromegalic animals while haemoglobin concentration, blood urea nitrogen, sodium and chloride ion concentrations, and urinary specific gravity, osmolality and fractional excretion of phosphate were significantly lower. Although, in the majority of cases clinicopathological abnormalities resolved following ovariohysterectomy, in one dog, acromegalic signs abated and insulin-like growth factor-1 concentrations normalised only following the surgical excision of mammary tumours carried out 2 months after ovariohysterectomy. The findings of this study indicate that GSDs are predisposed to the development of acromegaly with a suspected inherited susceptibility.

  19. Mammary fibroadenoma in a lamb

    PubMed Central

    Guvenc, Tolga; Yarim, Murat; Kabak, Yonca B.; Sozgen, Yuksel

    2007-01-01

    A fibroadenoma was diagnosed in the left udder of a 3-month-old female Chios lamb. No recurrence was observed after surgery. Grossly, the tumor had a whitish-gray lobular appearance, and the lobules were interlaced with thin septa. Microscopically, the tumor was composed of proliferating fibroepithelial tissue, including differentiated ducts lined by whorls and interlacing bundles of abundant loose fibrovascular stroma. Immunohistochemistry revealed the ductal epithelium to be positive for pancytokeratin (AE1/AE3) and loose fibrovascular stroma was positive for vimentin and basal cells covering the ductal epithelium of alpha-smooth-muscle actin. Immunostaining for the estrogen and progesterone receptors was negative. A diagnosis of mammary fibroadenoma was made based on the histological and immunohistochemical findings. PMID:17993758

  20. Identification of Mammary Specific Transcription Factors.

    DTIC Science & Technology

    1998-01-01

    per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and...release; distribution unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (Maximum 200 words) The Mouse Mammary Tumor Virus (MMTV) achieves its highest...levels of expression in the mammary glands of lactating mice . Previous work showed that the MMTV Long Terminal Repeat (LTR) has a modest level of

  1. 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.

  2. 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

  3. Role of Mammary Adenocarcinoma Cell Transterrin Response In Breast Cancer Metastasis

    DTIC Science & Technology

    1995-09-21

    for identifying dividing cells. Int. J. Cancer, 27::329-334. 13. Wrba, F., Ritzinger, E., Reiner, A., and Holzner , J.H. Transferrin receptor (TrfR...A., and Holzner , J.H. Transferrin receptor (TrfR) expression in breast carcinoma and its possible relationship to prognosis. An immunohistochemical

  4. Stem cells and the developing mammary gland.

    PubMed

    Makarem, Maisam; Spike, Benjamin T; Dravis, Christopher; Kannan, Nagarajan; Wahl, Geoffrey M; Eaves, Connie J

    2013-06-01

    The mammary gland undergoes dynamic changes throughout life. In the mouse, these begin with initial morphogenesis of the gland in the mid-gestation embryo followed by hormonally regulated changes during puberty and later in adulthood. The adult mammary gland contains a hierarchy of cell types with varying potentials for self-maintenance and differentiation. These include cells able to produce complete, functional mammary glands in vivo and that contain daughter cells with the same remarkable regenerative potential, as well as cells with more limited clonogenic activity in vitro. Here we review how applying in vitro and in vivo methods for quantifying these cells in adult mammary tissue to fetal mammary cells has enabled the first cells fulfilling the functional criteria of transplantable, isolated mammary stem cells to be identified a few days before birth. Thereafter, the number of these cells increases rapidly. Populations containing these fetal stem cells display growth and gene expression programs that differ from their adult counterparts but share signatures characteristic of certain types of breast cancer. Such observations reinforce growing evidence of important differences between tissue-specific fetal and adult cells with stem cell properties and emphasize the merits of investigating their molecular basis.

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

    ClinicalTrials.gov

    2017-02-08

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

  6. Association between environmental dust exposure and lung cancer in dogs.

    PubMed

    Bettini, Giuliano; Morini, Maria; Marconato, Laura; Marcato, Paolo Stefano; Zini, Eric

    2010-12-01

    The objective of this study was to investigate the relationship between the accumulation of black dust matter in lungs (anthracosis) and primary lung cancer in dogs. A retrospective study was carried out on material from 35 dogs with primary lung cancer and 160 controls. The amount, histological appearance and birefringence of anthracosis were assessed in pulmonary specimens by light microscopy, and the odds ratio (OR) calculated for dogs with primary lung cancer. The same factors were analysed to identify an association between tumour histotype, histological grade, and clinical stage. Papillary adenocarcinoma was most commonly diagnosed (45.7%). The majority of tumours were of histological grade II, and the lung cancer was more often localised (clinical stage I). An increased risk of lung cancer was observed in dogs with higher amounts of anthracosis (OR: 2.11, CI 95%: 1.20-3.70; P < 0.01), which suggests an association between anthracosis due to inhalation of polluted air and lung cancer in dogs.

  7. 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.

  8. Identification of six potential markers for the detection of circulating canine mammary tumour cells in the peripheral blood identified by microarray analysis.

    PubMed

    da Costa, A; Lenze, D; Hummel, M; Kohn, B; Gruber, A D; Klopfleisch, R

    2012-01-01

    The presence of circulating tumour cells (CTCs) in the peripheral blood is a prognostic factor for survival of human breast cancer patients. CTCs in the peripheral blood of dogs with mammary tumours have not been reported definitively. The present pilot study identifies mRNA markers for CTCs by comparing the transcriptome of canine mammary carcinoma cell lines CMM26 and CMM115 and peripheral blood leucocytes (PBLs). Genes with a 200-fold or higher mRNA expression in carcinoma cell lines were tested for specificity and sensitivity to detect CTCs using reverse transcriptase polymerase chain reaction (PCR). Six mRNA markers, AGR2, ATP8B1, CRYAB, F3 IRX3 and SLC1A1 were expressed in cell lines, but not PBL. All PCRs were able to detect one carcinoma cell admixed in 10(6) or more PBLs. The six mRNA markers may be suitable for detection of canine mammary CTCs and allow the analysis of their spatiotemporal distribution in dogs with mammary tumours.

  9. [An unusual secondary localization of bronchial adenocarcinoma].

    PubMed

    Mirallie, E; Courant, O; Sagan, C; Letessier, E; Paineau, J; Visset, J

    1993-01-01

    The authors report a rare case of metastatic carcinoma of the large bowel, secondary to a primary bronchogenic adenocarcinoma. Abdominal pain developed in a 44-year old man 5 months after lobectomy for lung adenocarcinoma. The diagnosis of a large caecal extraluminal mass was established by means of sonography, scanner and laparoscopy. Palliative resection (brain metastases) was performed. Postoperative histological examination revealed the resected tumor to be identical to the lung adenocarcinoma. The patient eventually died 4 months after resection (complication of intracranial hypertension). Diagnosis and therapeutic features of metastatic extra-thoracic lung carcinoma are discussed.

  10. [Mesocolic excision for colonic adenocarcinoma].

    PubMed

    Debove, Clotilde; Lefèvre, Jérémie H; Parc, Yann

    2017-02-01

    On the same principle than total mesorectal excision in rectal cancer, the effect of complete mesocolic excision on short and long-term outcomes is actually evaluated for colonic adenocarcinoma. This method, usually performed for left colectomy, offers a surgical specimen of higher quality, with a larger number of lymph nodes harvested. For right colectomy, surgical specifications make it less common complete mesocolic excision and conventional surgery offer comparable outcomes, as regards to postoperative morbidity and mortality rates. No differences are identified between laparoscopic and open surgery. On oncologic outcomes, only two studies report a higher free-disease survival after complete mesocolic excision. Then, there is evidence that complete mesocolic excision offers a higher rate of specimen with extensive lymph node resection, without increased morbidity rate. However, there is limited evidence that it leads to improve long-term oncological outcomes.

  11. Disease Precautions for Dog Walkers

    MedlinePlus

    ... make the dog ill. Dead rodents, wildlife or birds may present an irresistible temptation for many dogs, ... your care has been exposed to a toxin, call the owner and a veterinarian immediately. Dog walking ...

  12. Antiproliferative effect of berberine on canine mammary gland cancer cell culture.

    PubMed

    Sefidabi, Reyhaneh; Mortazavi, Pejman; Hosseini, Saeed

    2017-01-01

    Canine mammary gland tumors are the most frequent cause of cancer in female dogs. Numerous studies using cancer cell lines and clinical trials have indicated that various natural products and antioxidants reduce or possibly prevent the development of cancer. Berberine (BBR), the most important alkaloid in the Berberidaceae, which exerts a wide range of pharmacological and biochemical effects, has drawn much attention due to its particularly high antitumor activity in vitro and in animal studies. The aim of the present study was to investigate the antiproliferative effect of BBR against a canine mammary gland carcinoma cell line (CF41.Mg) in vitro. CF41.Mg cells were cultured in RPMI-1640 medium containing 10% heat inactived fetal bovine serum (FBS) and 100 mg/ml peniciline-streptomycin. Subsequently the cells were treated with different concentrations of BBR chloride (10, 25, 50, 100 and 200 µM) at a density of 12,000 cells/well in 96-well plates. Following treatment, the MTT assay was used to detect cell viability after 24-, 48- and 72-h incubations at 37°C with 5% CO2. The results indicated that BBR inhibited proliferation of canine mammary gland carcinoma cells, as treatment with 100 µM BBR for 24 h resulted in a significant decrease in cell viability (P<0.005). As the present study demonstrated that BBR (10-200 µM) induced cancer cell death, it is proposed that BBR may serve as a candidate agent against canine mammary tumor cells via its antiproliferative activity.

  13. Hormone signaling requirements for the conversion of non-mammary mouse cells to mammary cell fate(s) in vivo.

    PubMed

    Boulanger, Corinne A; Rosenfield, Sonia M; George, Andrea L; Smith, Gilbert H

    2015-06-01

    Mammotropic hormones and growth factors play a very important role in mammary growth and differentiation. Here, hormones including Estrogen, Progesterone, Prolactin, their cognate receptors, and the growth factor Amphiregulin, are tested with respect to their roles in signaling non-mammary cells from the mouse to redirect to mammary epithelial cell fate(s). This was done in the context of glandular regeneration in pubertal athymic female mice. Our previous studies demonstrated that mammary stem cell niches are recapitulated during gland regeneration in vivo. During this process, cells of exogenous origin cooperate with mammary epithelial cells to form mammary stem cell niches and thus respond to normal developmental signals. In all cases tested with the possible exception of estrogen receptor alpha (ER-α), hormone signaling is dispensable for non-mammary cells to undertake mammary epithelial cell fate(s), proliferate, and contribute progeny to chimeric mammary outgrowths. Importantly, redirected non-mammary cell progeny, regardless of their source, have the ability to self-renew and contribute offspring to secondary mammary outgrowths derived from transplanted chimeric mammary fragments; thus suggesting that some of these cells are capable of mammary stem cell/progenitor functions.

  14. Comparative aspects of mammary gland development and homeostasis.

    PubMed

    Capuco, Anthony V; Ellis, Steven E

    2013-01-01

    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, differentiation, lactation, and regression that are coordinated to provide nutrients for offspring or are driven by strategies to manage reproduction and milk production of domesticated species. Growth and maintenance of the mammary epithelium depends on the function of mammary stem cells and progenitor cells. In this review, we provide an overview of postnatal mammary gland development, cyclical phases of mammary gland regression (regression during lactation and between successive lactations), and mammary stem cells and progenitor cells. Where possible, these processes are related to animal production and compared across species, particularly bovine, porcine, murine, and human.

  15. Colonic adenocarcinoma with metastasis to the gingiva.

    PubMed

    Alvarez-Alvarez, Carlos; Iglesias-Rodríguez, Begoña; Pazo-Irazu, Susana; Delgado-Sánchez-Gracián, Carlos

    2006-01-01

    Metastatic tumors involve the oral cavity, and the most common primary sites are the breast and lung. Most cases affect the mandible and maxilla in that order, although some of them can be located in the soft perioral tissues. We report the case of a 62-year-old male who had been diagnosed with sigmoid adenocarcinoma with nodal and liver metastasis, who presented 6 months later with a gingival polypoid tumor, at first considered as a primary neoplasm of gingiva, that was diagnosed in a biopsy as metastatic intestinal adenocarcinoma. The histological evaluation is essential to separate adenocarcinoma from the commoner in this site squamous cell carcinoma, and the immunohistochemical techniques are useful to distinguish metastatic tumor versus primary adenocarcinoma from the minor salivary glands of the area. The intraoral spread of a disseminated neoplasm is generally a sign of bad prognosis, although a longer survival can be expected if a radical surgical treatment of a solitary metastasis is carried out.

  16. Service dogs. Final rule.

    PubMed

    2012-09-05

    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.

  17. USF-1 as an Inhibitor of Mammary Gland Carcinogenesis

    DTIC Science & Technology

    2002-09-01

    was targeted to the mammary gland under the control of the mouse mammary tumor virus (mmtv) long terminal repeat. Of eight lines of transgenic mice ...be explored by testing the hypothesis that targeted overexpression of USF-2 in the mammary glands of MMTV-myc transgenic mice will cause withdrawal...USF-2 under the control of the mouse mammary tumor virus long terminal repeat. Once in hand this new line of transgenic mice would be crossed with a

  18. Epigenetic reprogramming governs EcSOD expression during human mammary epithelial cell differentiation, tumorigenesis and metastasis

    PubMed Central

    Teoh-Fitzgerald, ML; Fitzgerald, MP; Zhong, W; Askeland, RW; Domann, FE

    2013-01-01

    Expression of the antioxidant enzyme EcSOD in normal human mammary epithelial cells was not recognized until recently. Although expression of EcSOD was not detectable in non-malignant human mammary epithelial cells (HMEC) cultured in conventional two-dimensional (2D) culture conditions, EcSOD protein expression was observed in normal human breast tissues, suggesting that the 2D-cultured condition induces a repressive status of EcSOD gene expression in HMEC. With the use of laminin-enriched extracellular matrix (lrECM), we were able to detect expression of EcSOD when HMEC formed polarized acinar structures in a 3D-culture condition. Repression of the EcSOD-gene expression was again seen when the HMEC acini were sub-cultured as a monolayer, implying that lrECM-induced acinar morphogenesis is essential in EcSOD-gene activation. We have further shown the involvement of DNA methylation in regulating EcSOD expression in HMEC under these cell culture conditions. EcSOD mRNA expression was strongly induced in the 2D-cultured HMEC after treatment with a DNA methyltransferase inhibitor. In addition, epigenetic analyses showed a decrease in the degree of CpG methylation in the EcSOD promoter in the 3D versus 2D-cultured HMEC. More importantly, >80% of clinical mammary adenocarcinoma samples showed significantly decreased EcSOD mRNA and protein expression levels compared with normal mammary tissues and there is an inverse correlation between the expression levels of EcSOD and the clinical stages of breast cancer. Combined bisulfite restriction analysis analysis of some of the tumors also revealed an association of DNA methylation with the loss of EcSOD expression in vivo. Furthermore, overexpression of EcSOD inhibited breast cancer metastasis in both the experimental lung metastasis model and the syngeneic mouse model. This study suggests that epigenetic silencing of EcSOD may contribute to mammary tumorigenesis and that restoring the extracellular superoxide scavenging

  19. Epigenetic reprogramming governs EcSOD expression during human mammary epithelial cell differentiation, tumorigenesis and metastasis.

    PubMed

    Teoh-Fitzgerald, M L; Fitzgerald, M P; Zhong, W; Askeland, R W; Domann, F E

    2014-01-16

    Expression of the antioxidant enzyme EcSOD in normal human mammary epithelial cells was not recognized until recently. Although expression of EcSOD was not detectable in non-malignant human mammary epithelial cells (HMEC) cultured in conventional two-dimensional (2D) culture conditions, EcSOD protein expression was observed in normal human breast tissues, suggesting that the 2D-cultured condition induces a repressive status of EcSOD gene expression in HMEC. With the use of laminin-enriched extracellular matrix (lrECM), we were able to detect expression of EcSOD when HMEC formed polarized acinar structures in a 3D-culture condition. Repression of the EcSOD-gene expression was again seen when the HMEC acini were sub-cultured as a monolayer, implying that lrECM-induced acinar morphogenesis is essential in EcSOD-gene activation. We have further shown the involvement of DNA methylation in regulating EcSOD expression in HMEC under these cell culture conditions. EcSOD mRNA expression was strongly induced in the 2D-cultured HMEC after treatment with a DNA methyltransferase inhibitor. In addition, epigenetic analyses showed a decrease in the degree of CpG methylation in the EcSOD promoter in the 3D versus 2D-cultured HMEC. More importantly, >80% of clinical mammary adenocarcinoma samples showed significantly decreased EcSOD mRNA and protein expression levels compared with normal mammary tissues and there is an inverse correlation between the expression levels of EcSOD and the clinical stages of breast cancer. Combined bisulfite restriction analysis analysis of some of the tumors also revealed an association of DNA methylation with the loss of EcSOD expression in vivo. Furthermore, overexpression of EcSOD inhibited breast cancer metastasis in both the experimental lung metastasis model and the syngeneic mouse model. This study suggests that epigenetic silencing of EcSOD may contribute to mammary tumorigenesis and that restoring the extracellular superoxide scavenging

  20. Pathologic classification of adenocarcinoma of lung.

    PubMed

    Van Schil, Paul E; Sihoe, Alan D L; Travis, William D

    2013-10-01

    Recently, the 1999/2004 World Health Organization (WHO) classification of adenocarcinoma became less useful from a clinical standpoint as most adenocarcinomas belonged to the mixed subtype and the term bronchioloalveolar carcinoma (BAC) gave rise to much confusion among clinicians. For these reasons a new adenocarcinoma classification was introduced in 2011 by a joint working group of the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS). This represents an international, multidisciplinary effort joining pathologists, molecular biologists, pulmonary physicians, thoracic oncologists, radiologists, and thoracic surgeons. Currently, a distinction is made between pre-invasive lesions, minimally invasive and invasive lesions. The confusing term BAC is not used anymore and new subcategories include adenocarcinoma in situ and minimally invasive adenocarcinoma. Several aspects of this classification are discussed with main emphasis on its correlation with imaging techniques and its impact on diagnosis, treatment and prognosis. On chest computed tomography (CT) a distinction is made between solid and subsolid nodules, the latter comprising ground glass opacities (GGO), and partly solid lesions. Several studies incorporating CT and positron emission tomographic (PET) data show a good imaging-pathologic correlation. With the implementation of screening programs early lung cancer has become a hotly debated topic and sublobar resection is currently reconsidered for early lesions without lymph node involvement. This new classification will also have an impact on the TNM classification. Thoracic surgeons will continue to play a major role in the application, evaluation and further refinement of this new adenocarcinoma classification.

  1. Pigmented mammary paget disease misdiagnosed as malignant melanoma.

    PubMed

    Lee, Ji Hye; Kim, Tae Hyung; Kim, Soo-Chan; Kim, You Chan; Roh, Mi Ryung

    2014-12-01

    Pigmented mammary Paget disease is a very rare clinicopathologic variant of mammary Paget disease. Diagnosis is often difficult because its clinical and histological features are very similar to those of malignant melanoma. Herein, we report a case of pigmented mammary Paget disease misdiagnosed as malignant melanoma.

  2. 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...

  3. Yin Yang 1 cooperates with activator protein 2 to stimulate ERBB2 gene expression in mammary cancer cells.

    PubMed

    Begon, Dominique Y; Delacroix, Laurence; Vernimmen, Douglas; Jackers, Pascale; Winkler, Rosita

    2005-07-01

    Overexpression of the ERBB2 oncogene is observed in about 30% of breast cancers and is generally correlated with a poor prognosis. Previous results from our and other laboratories indicated that elevated transcriptional activity contributes significantly to the overexpression of ERBB2 mRNA in mammary adenocarcinoma cell lines. Activator protein 2 (AP-2) transcription factors account for this overexpression through two recognition sequences located 215 and 500 bp upstream from the transcription start site. Furthermore, AP-2 transcription factors are highly expressed in cancer cell lines overexpressing ERBB2. In this report, we examined the cooperative effect of Yin Yang 1 (YY1) on AP-2-induced activation of ERBB2 promoter activity. We detected high levels of YY1 transcription factor in mammary cancer cell lines. Notably, we showed that YY1 enhances AP-2alpha transcriptional activation of the ERBB2 promoter through an AP-2 site both in HepG2 and in HCT116 cells, whereas a carboxyl-terminal-truncated form of YY1 cannot. Moreover, we demonstrated the interaction between endogenous AP-2 and YY1 factors in the BT-474 mammary adenocarcinoma cell line. In addition, inhibition of endogenous YY1 protein by an antisense decreased the transcription of an AP-2-responsive ERBB2 reporter plasmid in BT-474 breast cancer cells. Finally, we detected in vivo AP-2 and YY1 occupancy of the ERBB2 proximal promoter in chromatin immunoprecipitation assays. Our data thus provide evidence that YY1 cooperates with AP-2 to stimulate ERBB2 promoter activity through the AP-2 binding sites.

  4. Myc is a Notch1 transcriptional target and a requisite for Notch1-induced mammary tumorigenesis in mice.

    PubMed

    Klinakis, Apostolos; Szabolcs, Matthias; Politi, Katerina; Kiaris, Hippokratis; Artavanis-Tsakonas, Spyros; Efstratiadis, Argiris

    2006-06-13

    To explore the potential involvement of aberrant Notch1 signaling in breast cancer pathogenesis, we have used a transgenic mouse model. In these animals, mouse mammary tumor virus LTR-driven expression of the constitutively active intracellular domain of the Notch1 receptor (N1(IC)) causes development of lactation-dependent mammary tumors that regress upon gland involution but progress to nonregressing, invasive adenocarcinomas in subsequent pregnancies. Up-regulation of Myc in these tumors prompted a genetic investigation of a potential Notch1/Myc functional relationship in breast carcinogenesis. Conditional ablation of Myc in the mammary epithelium prevented the induction of regressing N1(IC) neoplasms and also reduced the incidence of nonregressing carcinomas, which developed with significantly increased latency. Molecular analyses revealed that both the mouse and human Myc genes are direct transcriptional targets of N1(IC) acting through its downstream Cbf1 transcriptional effector. Consistent with this mechanistic link, Notch1 and Myc expression is positively correlated by immunostaining in 38% of examined human breast carcinomas.

  5. Mammary phenotypic expression induced in epidermal cells by embryonic mammary mesenchyme.

    PubMed

    Cunha, G R; Young, P; Christov, K; Guzman, R; Nandi, S; Talamantes, F; Thordarson, G

    1995-01-01

    The goal of this research was to establish methods for inducing mammary epithelial differentiation from nonmammary epithelium. For this purpose, mid-ventral or dorsal epidermis (skin epithelium; SKE) from 13-day rat or mouse embryos was associated with 13-day embryonic mouse mammary mesenchyme (mammary gland mesenchyme; MGM) (mouse MGM+rat or mouse SKE). The resultant MGM+SKE recombinants as well as controls (homotypic mouse mammary recombinants, homotypic mouse skin recombinants and mouse mammary mesenchyme by itself) were grafted under the renal capsule of syngeneic or athymic female nude mouse hosts. Most female hosts were induced to undergo lactogenesis by grafting an adult pituitary which elicited a state of hyperprolactinemia. Tissue recombinants of mouse MGM+rat or mouse SKE grown for 1 month in vivo formed a hair-bearing keratinized skin from which mammary ductal structures extended into the mesenchyme. The ducts were composed of columnar luminal epithelial cells as well as basal, actin-positive myoepithelial cells. When grown in pituitary-grafted hosts, the ductal epithelial cells expressed casein and alpha-lactalbumin as judged by immunocytochemistry. The expression of caseins in MGM+SKE recombinants was confirmed by Western blot. The epithelial cells in mouse MGM+rat SKE recombinants expressing milk proteins were shown to be rat cells while the surrounding connective tissue was composed of mouse cells based upon staining with Hoechst dye 33258. Using mammary-specific markers, these studies confirmed the earlier morphological studies of Propper and unequivocally demonstrated for the first time that embryonic mammary mesenchyme can induce morphological and functional mammary differentiation from nonmammary epithelium.

  6. 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

  7. Adenosquamous carcinoma of the oesophagus in a dog.

    PubMed

    Okanishi, H; Shibuya, H; Miyasaka, T; Asano, K; Sato, T; Watari, T

    2015-08-01

    A six-year-old mixed-breed male dog weighing 7.0 kg was presented with chronic vomiting and regurgitation. Endoscopic examination revealed prominent oesophageal dilation in the thoracic region, multiple small greyish-white nodules over the oesophageal lumen and cauliflower-like masses in the caudal oesophagus. Histopathological studies revealed a characteristic pattern of coexisting elements of infiltrating adenocarcinoma and squamous cell carcinoma. Immunohistochemical staining with anti-cytokeratin AE1 + AE3 was positive in both types of neoplastic cells. Neoplastic glandular cells stained positively for cytokeratin 8 while neoplastic squamous cells stained positively for cytokeratin 5/6. On the basis of these findings, the dog was diagnosed with oesophageal adenosquamous carcinoma. The case history and findings suggest that the malignancy might have developed from Barrett's oesophagus following irritation of the oesophageal mucosa due to chronic vomiting and regurgitation.

  8. CEACAM1 controls the EMT switch in murine mammary carcinoma in vitro and in vivo

    PubMed Central

    Gerstel, Daniela; von Ehrenstein, Lena; Einhoff, Julia; Schmidt, Geske; Logsdon, Matthew; Brandner, Johanna; Tiegs, Gisa; Beauchemin, Nicole; Wagener, Christoph; Deppert, Wolfgang; Horst, Andrea Kristina

    2016-01-01

    We analyzed the molecular basis for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)-controlled inhibition of epithelial-mesenchymal transition (EMT) in a mouse model for mammary adenocarcinoma (WAP-T mice). We demonstrate that silencing of CEACAM1 in WAP-T tumor-derived G-2 cells induces epithelial-mesenchymal plasticity (EMP), as evidenced by typical changes of gene expression, morphology and increased invasion. In contrast, reintroduction of CEACAM1 into G-2 cells reversed up-regulation of genes imposing mesenchymal transition, as well as cellular invasion. We identified the Wnt-pathway as target for CEACAM1-mediated repression of EMT. Importantly, β-catenin phosphorylation status and transcriptional activity strongly depend on CEACAM1 expression: CEACAM1high G-2 cells displayed enhanced phosphorylation of β-catenin at S33/S37/T41 and decreased phosphorylation at Y86, thereby inhibiting canonical Wnt/β-catenin signaling. We identified Src-homology 2 domain-containing phosphatase 2 (SHP-2) as a critical binding partner of CEACAM1 that could modulate β-catenin Y86 phosphorylation. Hence, CEACAM1 serves as a scaffold that controls membrane proximal β-catenin signaling. In vivo, mammary tumors of WAP-T/CEACAM1null mice displayed increased nuclear translocation of β-catenin and a dramatically enhanced metastasis rate compared to WAP-T mice. Hence, CEACAM1 controls EMT in vitro and in vivo by site-specific regulation of β-catenin phosphorylation. Survival analyses of human mammary carcinoma patients corroborated these data, indicating that CEACAM1 is a prognostic marker for breast cancer survival. PMID:27572314

  9. CEACAM1 controls the EMT switch in murine mammary carcinoma in vitro and in vivo.

    PubMed

    Wegwitz, Florian; Lenfert, Eva; Gerstel, Daniela; von Ehrenstein, Lena; Einhoff, Julia; Schmidt, Geske; Logsdon, Matthew; Brandner, Johanna; Tiegs, Gisa; Beauchemin, Nicole; Wagener, Christoph; Deppert, Wolfgang; Horst, Andrea Kristina

    2016-09-27

    We analyzed the molecular basis for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)-controlled inhibition of epithelial-mesenchymal transition (EMT) in a mouse model for mammary adenocarcinoma (WAP-T mice). We demonstrate that silencing of CEACAM1 in WAP-T tumor-derived G-2 cells induces epithelial-mesenchymal plasticity (EMP), as evidenced by typical changes of gene expression, morphology and increased invasion. In contrast, reintroduction of CEACAM1 into G-2 cells reversed up-regulation of genes imposing mesenchymal transition, as well as cellular invasion. We identified the Wnt-pathway as target for CEACAM1-mediated repression of EMT. Importantly, β-catenin phosphorylation status and transcriptional activity strongly depend on CEACAM1 expression: CEACAM1high G-2 cells displayed enhanced phosphorylation of β-catenin at S33/S37/T41 and decreased phosphorylation at Y86, thereby inhibiting canonical Wnt/β-catenin signaling. We identified Src-homology 2 domain-containing phosphatase 2 (SHP-2) as a critical binding partner of CEACAM1 that could modulate β-catenin Y86 phosphorylation. Hence, CEACAM1 serves as a scaffold that controls membrane proximal β-catenin signaling. In vivo, mammary tumors of WAP-T/CEACAM1null mice displayed increased nuclear translocation of β-catenin and a dramatically enhanced metastasis rate compared to WAP-T mice. Hence, CEACAM1 controls EMT in vitro and in vivo by site-specific regulation of β-catenin phosphorylation. Survival analyses of human mammary carcinoma patients corroborated these data, indicating that CEACAM1 is a prognostic marker for breast cancer survival.

  10. Mammary stem cells have myoepithelial cell properties

    PubMed Central

    Prater, Michael D.; Petit, Valérie; Russell, I. Alasdair; Giraddi, Rajshekhar; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F.; Metzger, Daniel; Faraldo, Marisa M.; Deugnier, Marie-Ange; Glukhova, Marina A.; Stingl, John

    2014-01-01

    Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976

  11. 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.

  12. 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.

  13. 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.

  14. Breast metastasis from a pulmonary adenocarcinoma: Case report and review of the literature

    PubMed Central

    SANGUINETTI, ALESSANDRO; PUMA, FRANCESCO; LUCCHINI, ROBERTA; SANTOPRETE, STEFANO; CIROCCHI, ROBERTO; CORSI, ALESSIA; TRIOLA, ROBERTA; AVENIA, NICOLA

    2013-01-01

    Breast metastasis from extra-mammary malignancy is rare. An incidence of 0.4–1.3% has been reported in the literature. The primary malignancies most commonly metastasizing to the breast are leukemia, lymphoma and malignant melanoma. We present a case of metastasis to the breast from a pulmonary adenocarcinoma, diagnosed concomitantly with the primary tumor. A 43-year-old female presented with dyspnea and a dry cough of 3 weeks’ duration. A subsequent chest radiograph revealed a massive pleural effusion. Additionally, on physical examination, a poorly defined mass was noted in the upper outer quadrant of the right breast. The patient underwent bronchoscopy, simple right mastectomy and medical thoracoscopy. Following cytology, histology and immunohistochemistry, primary lung adenocarcinoma with metastasis to the breast and parietal pleura was diagnosed. Histologically, both the primary and metastatic anatomic sites demonstrated a micropapillary component, which has recently been recognized as an important prognostic factor. Although the patient received chemotherapy, she succumbed to her condition within 8 months. Accurate differentiation of metastasis from primary carcinoma is very important as the treatment and prognosis of the two differ significantly. PMID:23255943

  15. Breast metastasis from a pulmonary adenocarcinoma: Case report and review of the literature.

    PubMed

    Sanguinetti, Alessandro; Puma, Francesco; Lucchini, Roberta; Santoprete, Stefano; Cirocchi, Roberto; Corsi, Alessia; Triola, Roberta; Avenia, Nicola

    2013-01-01

    Breast metastasis from extra-mammary malignancy is rare. An incidence of 0.4-1.3% has been reported in the literature. The primary malignancies most commonly metastasizing to the breast are leukemia, lymphoma and malignant melanoma. We present a case of metastasis to the breast from a pulmonary adenocarcinoma, diagnosed concomitantly with the primary tumor. A 43-year-old female presented with dyspnea and a dry cough of 3 weeks' duration. A subsequent chest radiograph revealed a massive pleural effusion. Additionally, on physical examination, a poorly defined mass was noted in the upper outer quadrant of the right breast. The patient underwent bronchoscopy, simple right mastectomy and medical thoracoscopy. Following cytology, histology and immunohistochemistry, primary lung adenocarcinoma with metastasis to the breast and parietal pleura was diagnosed. Histologically, both the primary and metastatic anatomic sites demonstrated a micropapillary component, which has recently been recognized as an important prognostic factor. Although the patient received chemotherapy, she succumbed to her condition within 8 months. Accurate differentiation of metastasis from primary carcinoma is very important as the treatment and prognosis of the two differ significantly.

  16. Characterization of Human Mammary Epithelial Stem Cells

    DTIC Science & Technology

    2009-10-01

    Appendix……………………………………………………………………………… 11 Eirew,P., Stingl,J., Raouf,A., Turashvili,G., Aparicio ,S., Emerman,J.T., and Eaves,C.J. A method for... Aparicio , Joanne Emerman and Connie Eaves. A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability...Abstracts Peter Eirew, John Stingl, Afshin Raouf, Gulisa Turshvili, Sam Aparicio , Joanne Emerman and Connie Eaves, “Identification of Human Mammary

  17. Biomarkers of metastatic potential in cultured adenocarcinoma clones.

    PubMed

    Dabbous, Mustafa Kh; Jefferson, M Margaret; Haney, Lena; Thomas, Edwin L

    2011-02-01

    Two-dimensional isoelectric focusing and gel electrophoresis followed by mass spectrometry were used to detect, measure, and identify changes in protein expression correlated with differences in the metastatic potential of cultured rat mammary adenocarcinoma cells. MTC is a non-metastatic cell clone derived from a primary tumor. MTLn2 and MTLn3 are low and high metastatic potential cell clones derived from lung metastases of the primary tumor. A total of 1,500 proteins was detected. The patterns of protein expression of MTLn2 and MTLn3 cells were similar. Only five spots had a threefold or greater statistically significant difference in staining intensity between MTLn2 and MTLn3 cells, whereas 70 spots differed between MTC and MTLn3 cells. Twenty spots were selected for further study, ten that had a positive correlation of staining intensity with metastatic potential and ten that had a negative (inverse) correlation. Of the 17 unique proteins that were identified, five have often been cited as tumor biomarkers. These included the positive biomarkers nucleophosmin (NPM) and 14-3-3 protein sigma and the negative biomarkers raf kinase inhibitor protein (RKIP), peroxiredoxin-2, and galectin-1. The only identified protein that was markedly higher in MTLn3 cells than in the less-metastatic MTLn2 cells was 14-3-3 protein sigma. The results indicate that increased metastatic potential is associated with positive and negative changes in expression of particular proteins. Proteins that are positively correlated with metastatic potential may prove more useful as clinical biomarkers, but those with negative correlations may still provide useful information about underlying mechanisms of metastatic spread.

  18. Antiproliferative Effects of Oxytocin and Desmopressin on Canine Mammary Cancer Cells

    PubMed Central

    Benavente, Micaela Andrea; Bianchi, Carolina Paula; Imperiale, Fernanda; Aba, Marcelo Alfredo

    2016-01-01

    Neoplasms of the mammary gland represent the most frequent tumor type in the female dog, and according to the histologic criteria, approximately 50% of them are malignant. In the most aggressive cases of mammary cancer, surgery is not enough to warrant a favorable outcome, and adjuvant therapies are needed to improve the patient’s overall survival. The aim of the present study was to evaluate the effects of two peptides on proliferation of a canine mammary cancer cell line derived from a simple carcinoma. The cell line CMT-U27 was grown in 96-well plates, at two cell densities (4 × 103 and 8 × 103 cells/well). Cultures were treated with oxytocin (OT) or desmopressin at five concentrations (10, 50, 100, 500, and 1000 nM). After 72 h of incubation, cell proliferation was determined by the MTT assay. Results showed that with 4 × 103 cells/well, OT at 50, 500, and 1000 nM was growth inhibitory for the cells, being statistically significant at 1000 nM. On the contrary, no antiproliferative effect was observed with 10 or 100 nM. At 8 × 103 cells/well, OT showed a significant antiproliferative effect only with the highest concentration (1000 nM). Desmopressin at 4 × 103 cells/well decreased cell viability at concentrations of 50, 100, 500, and 1000 nM (statistically significant with the highest concentration), while no effect was observed with 10 nM. With 8 × 103 cells/well, this peptide reduced cell growth at 100, 500, and 1000 nM. In conclusion, we suggest that these peptides may be potential and promising compounds for the treatment of dogs with simple carcinomas of the mammary gland. In vivo studies are required to confirm this hypothesis. PMID:28083539

  19. 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

  20. Positional variations in mammary gland development and cancer.

    PubMed

    Veltmaat, Jacqueline M; Ramsdell, Ann F; Sterneck, Esta

    2013-06-01

    Most mammals develop their mammary glands in pairs of which the two counterparts are symmetrically displaced away from the ventral midline. Based on this symmetry and the same functional outcome as a milk-producing organ, the mammary glands are easily presumed to be mere copies of one another. Based on our analysis of published data with inclusion of new results related to mammary development and pathology in mice, we argue that this presumption is incorrect: Between and within pairs, mammary glands differ from one another, and tumor incidence and biology depend on the position along the anterior-posterior and the left-right axis as well. This insight has implications for experimental designs with mouse models and for data extrapolation between mammary glands within and between species. We suggest that improved documentation of location-specific mammary gland features will lead to more insights into the molecular mechanisms of mammary gland development and cancer biology in both mice and humans.

  1. Cooperativity of E-cadherin and Smad4 Loss to Promote Diffuse-type Gastric Adenocarcinoma and Metastasis

    PubMed Central

    Park, Jun Won; Jang, Seok Hoon; Park, Dong Min; Lim, Na Jung; Deng, Chuxia; Kim, Dae Yong; Green, Jeffrey E.; Kim, Hark Kyun

    2014-01-01

    Loss of E-cadherin (CDH1), Smad4 and p53 have all been shown to play an integral role in gastric, intestinal and breast cancer formation. Compound conditional knockout mice for Smad4, p53, and E-cadherin were generated to define and compare the roles of these genes in gastric, intestinal and breast cancer development by crossing with Pdx-1-Cre, Villin-Cre and MMTV-Cre transgenic mice. Interestingly, gastric adenocarcinoma was significantly more frequent in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice than in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1+/+ mice, demonstrating that Cdh1 heterozygosity accelerates the development and progression of gastric adenocarcinoma, in combination with loss of Smad4 and p53. Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice developed gastric adenocarcinomas without E-cadherin expression. However, intestinal and mammary adenocarcinomas with the same genetic background retained E-cadherin expression and were phenotypically similar to mice with both wild-type Cdh1 alleles. Lung metastases were identified in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice, but not in the other genotypes. Nuclear β-catenin accumulation was identified at the invasive tumor front of gastric adenocarcinomas arising in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice. This phenotype was less prominent in mice with intact E-cadherin or Smad4, indicating that the inhibition of β-catenin signaling by E-cadherin or Smad4 down-regulates signaling pathways involved in metastases in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice. Knockdown of β-catenin significantly inhibited migratory activity of Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ cell lines. Thus, loss of E-cadherin and Smad4 cooperate with p53 loss to promote the development and metastatic progression of gastric adenocarcinomas, with similarities to human gastric adenocarcinoma. Implications This study demonstrates that inhibition of β-catenin is a converging node for the anti-metastatic signaling pathways driven by E-cadherin and Smad4 in Pdx-1

  2. Mammary Cancer and Activation of Transposable Elements

    DTIC Science & Technology

    2014-09-01

    AD_________________ AWARD NUMBER: W81XWH-11-1-0401 TITLE: Mammary Cancer and Activation of Transposable Elements PRINCIPAL INVESTIGATOR...way as transcripts from the regular gene promoter. Transcriptional activation of retrotransposons is strongly linked with their CpG DNA methylation

  3. 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...

  4. What Happens After Treatment for Small Intestine Adenocarcinoma?

    MedlinePlus

    ... After Treatment What Happens After Treatment for Small Intestine Adenocarcinoma? For some people with small intestine cancer, ... Small Intestine Adenocarcinoma Stops Working More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  5. What Should You Ask Your Doctor About Small Intestine Adenocarcinoma?

    MedlinePlus

    ... What Should You Ask Your Doctor About Small Intestine Adenocarcinoma? It’s important to have honest, open discussions ... Doctor About Small Intestine Adenocarcinoma? More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  6. Molecular cytogenetic characterization of mammary neuroendocrine carcinoma.

    PubMed

    Xiang, De-Bing; Wei, Bing; Abraham, Susan C; Huo, Lei; Albarracin, Constance T; Zhang, Hong; Babiera, Gildy; Caudle, Abigail S; Akay, Catherine L; Rao, Pulivarthi; Zhao, Yi-Jue; Lu, Xinyan; Wu, Yun

    2014-09-01

    Primary mammary neuroendocrine carcinoma (NEC) is an uncommon entity that accounts for 2% to 5% of breast carcinomas. Recent reports have shown that NEC of the breast is an aggressive subtype of mammary carcinoma that is distinct from invasive ductal carcinoma, not otherwise specified, and have suggested that these tumors have a poorer prognosis than invasive ductal carcinoma, not otherwise specified. In this study, we provide the first cytogenetic characterization of mammary NEC using both conventional G-banding and spectral karyotype on a group of 7 tumors. We identified clonal chromosomal aberrations in 5 (71.4%) cases, with 4 of them showing complex karyotypes. Of these, recurrent numerical aberrations included gain of chromosome 7 (n = 2) and loss of chromosome 15 (n = 2). Recurrent clonal structural chromosomal aberrations involved chromosomes 1 (n = 3), 3 (n = 2), 6q (n = 3), and 17q (n = 3). Of the 4 (57.1%) cases with complex karyotypes, 2 showed evidence of chromothripsis, a phenomenon in which tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. One of these had evidence of chromothripsis involving chromosomes 1, 6, 8, and 15. The other also had evidence of chromosome 8 chromothripsis, making this a recurrent finding shared by both cases. We also found that mammary NEC shared some cytogenetic abnormalities--such as trisomy 7 and 12--with other neuroendocrine tumors in the lung and gastrointestinal tract, suggesting trisomy 7 and 12 as potential common molecular aberrations in neuroendocrine tumors. To our knowledge, this is the first report on molecular cytogenetic characterization of mammary NEC.

  7. Radiographic characterization of primary lung tumors in 74 dogs.

    PubMed

    Barrett, Laura E; Pollard, Rachel E; Zwingenberger, Allison; Zierenberg-Ripoll, Alexandra; Skorupski, Katherine A

    2014-01-01

    Primary pulmonary neoplasia is well recognized in dogs and prognosis depends upon the tumor type. The purpose of this retrospective study was to characterize the radiographic appearance of different primary lung tumors with the goal of establishing imaging criteria to separate the different types. Three-view thoracic radiographs of 74 dogs with histologically confirmed pulmonary anaplastic carcinoma (n = 2), adenocarcinoma (n = 31), bronchioalveolar carcinoma (n = 19), histiocytic sarcoma (n = 21), and squamous cell carcinoma (n = 1) were evaluated. Radiographs were assessed for tumor volume, affected lobe, location within lobe, overall pulmonary pattern, presence of cavitation, mineralization, air bronchograms, lymphadenomegaly, and pleural fluid. Histiocytic sarcomas were significantly larger than other tumor types (271 cm(3); P = 0.009) and most likely to be found in the left cranial (38%; 8/21) and right middle (43%; 9/21) lung lobes, whereas adenocarcinomas were most likely to be found in the left caudal (29%; 9/31) lung lobe. Fifty-seven percent (12/21) of histiocytic sarcomas had an internal air bronchogram. Findings indicate that a large mass in the periphery or affecting the whole lobe of the right middle or left cranial lung lobe with an internal air bronchogram is likely to be an histiocytic sarcoma.

  8. Adenocarcinoma of Meckel's cave: case report.

    PubMed

    Tacconi, L; Arulampalam, T; Johnston, F; Symon, L

    1995-12-01

    A rare localization of adenocarcinoma in Meckel's cave is reported in a 58-year-old woman, who had a 5-month history of pain and altered sensation in the second division of the left trigeminal nerve. Removal of the lesion was achieved by a subtemporal route. Histology showed this to be an adenocarcinoma. The patient underwent investigations for a primary tumor; the investigations were all negative, and the patient was subsequently treated with a course of radiotherapy. At 4-month follow-up, there was no evidence of recurrence, and she remains symptomatically well. The various mechanisms of secondary localization are discussed.

  9. Dog and owner demographic characteristics and dog personality trait associations.

    PubMed

    Kubinyi, Eniko; Turcsán, Borbála; Miklósi, Adám

    2009-07-01

    The aim of this study was to analyze the relationships between four personality traits (calmness, trainability, dog sociability and boldness) of dogs (Canis familiaris) and dog and owner demographics on a large sample size with 14,004 individuals. German speaking dog owners could characterize their dog by filling out a form on the Internet. There were five demographic variables for dogs and nine for owners. Two statistical methods were used for investigating the associations between personality and demographic traits: the more traditional general linear methods and regression trees that are ideal for analyzing non-linear relationships in the structure of the data. The results showed that calmness is influenced primarily by the dog's age, the neutered status, the number of different types of professional training courses (e.g. obedience, agility) the dog had experienced and the age of acquisition. The least calm dogs were less than 2.5 years old, neutered and acquired after the first 12 weeks of age, while the calmest dogs were older than 6.9 years. Trainability was affected primarily by the training experiences, the dog's age, and the purpose of keeping the dog. The least trainable dogs had not received professional training at all and were older than 3 years. The most trainable dogs were those who participated in three or more types of professional training. Sociability toward conspecifics was mainly determined by the age, sex, training experience and time spent together. The least sociable dogs were older than 4.8 years and the owners spent less than 3h with the dog daily. The most sociable dogs were less than 1.5 years old. Males were less sociable toward their conspecifics than females. Boldness was affected by the sex and age of the dog and the age of acquisition. The least bold were females acquired after the age of 1 year or bred by the owner. The boldest dogs were males, acquired before the age of 12 weeks, and were younger than 2 years old. Other variables

  10. 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.

  11. 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

  12. 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.

  13. CDP Is a Repressor of Mouse Mammary Tumor Virus Expression in the Mammary Gland

    PubMed Central

    Zhu, Quan; Gregg, Keqin; Lozano, Mary; Liu, Jinqi; Dudley, Jaquelin P.

    2000-01-01

    Mouse mammary tumor virus (MMTV) transcription is highest in the lactating mammary gland but is detectable in a variety of other tissues. Previous results have shown that MMTV expression is suppressed in lymphoid and other tissues through the binding of the homeodomain-containing repressor special AT-rich binding protein 1 to a negative regulatory element (NRE) in the MMTV long terminal repeat (LTR). Another homeoprotein repressor, CCAAT displacement protein (CDP), also binds to the MMTV NRE, but a role for CDP in MMTV transcriptional suppression has not yet been demonstrated. In this paper, we show that the level of CDP decreases during development of the mammary gland and that this decline in CDP level correlates with the known increase in MMTV expression observed during mammary gland differentiation. Moreover, CDP overexpression was able to suppress MMTV LTR-reporter gene activity up to 20-fold in transient-transfection assays of mouse mammary cells. To determine if this effect was due to direct binding of CDP to the promoter-proximal NRE, we performed DNase I protection assays to map two CDP-binding sites from +835 to +845 and +920 to +931 relative to the first base of the LTR. Mutations engineered into each of these sites decreased CDP binding to the proximal NRE, whereas a combination of these mutations further reduced binding. Subsequently, each of these mutations was introduced into the full-length MMTV LTR upstream of the luciferase reporter gene. Analysis of stable transfectants of LTR constructs showed that CDP binding site mutations in the proximal NRE elevated reporter gene expression two- to sixfold compared to wild-type LTR constructs. Thus, MMTV expression increases during mammary gland development, in part due to decreased CDP levels and CDP binding to the LTR. Together, these experiments provide the first evidence that CDP acts as a repressor of MMTV transcription in the mammary gland. PMID:10864645

  14. 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.

  15. Breed-related differences in altered BRCA1 expression, phenotype and subtype in malignant canine mammary tumors.

    PubMed

    Im, Keum-Soon; Kim, Il-Hwan; Kim, Na-Hyun; Lim, Ha-Young; Kim, Jong-Hyuk; Sur, Jung-Hyang

    2013-03-01

    BRCA1 is a high-penetrance breast cancer susceptibility gene and BRCA1-associated breast cancer has a high familial prevalence that is more common among certain populations of humans. A similar high prevalence also exists for canine mammary tumors (CMTs) and the objective of this study was to determine the breed-related differences in malignant CMTs. Comparative analyses of the expression of various prognostic factors for CMTs, including BRCA1, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) were conducted on 139 malignant CMT cases from five breeds with the highest prevalence of CMTs in Korea. Significant breed-related differences were observed in the expression of BRCA1 (P=0.003), histological grade (P=0.038), and extensive lymphatic invasion (P=0.042). The Shih Tzu breed had the highest proportion of dogs with malignant CMT and strong overexpression of BRCA1. Cytoplasmic and membranous expression of BRCA1 was associated with the ER negative (P=0.004), PR negative (P=0.046), and triple negative (ER, PR, and HER-2 negative; P=0.016) phenotype and the basal-like molecular subtype (P=0.019) in Shih Tzu dogs. Since these features are similar to BRCA1-related human breast cancer, dogs with BRCA1-associated CMT, particularly Shih Tzu dogs, may serve as a suitable spontaneous model, although additional molecular studies are needed.

  16. Fungal rhinitis in dogs.

    PubMed

    Ostrzeszewicz, M; Sapierzyński, R

    2015-01-01

    Fungal rhinitis and sinusitis in dogs are quite common reasons of chronic nasal discharge and rhinoscopy in such cases is commonly suggested. Forty three dogs were examined using rhinoscopy because of the presence of chronic airway symptoms. Clinical examination, routine hematology and serum biochemistry profiles, nasal and frontal sinus radiographs were made in all animals. Additionally, computed tomography in one dog was performed. Samples for histopathology were taken from 9 patients during rhinoscopy, additionally, from 8 of these patients samples for cytopathology were collected by blind nasal swab technique. In 9 of 43 dogs (20,5%), all males aged 1 to 13 years, examinations led to a diagnosis of fungal rhinitis. In 2 cases a diagnosis of fungal rhinitis was obtained based solely on cytopathology, while in 7 cases - mycosis of nasal mucosa was confirmed by histopathology. The present study revealed that cytopathological examination of nasal swabs has a low diagnostic value in the case of nasal infections in dogs. Although, in some dogs cytopathology, together with other widely available diagnostic techniques was sufficient to reliably diagnose fungal rhinitis, histopathology of samples collected during rhinoscopy is still the gold standard in such cases.

  17. [Exaggerated breed characteristics in dogs].

    PubMed

    Wilting, M M; Endenburg, N

    2012-01-01

    Dutch dog owners seem to be aware of bad dog breeding practices with regard to exaggerated breed characteristics that are detrimental to the dog's welfare. Yet they do not always look for these features when buying a dog. Most dog owners think that veterinarians could have an important role in preventing these exaggerated physical traits, by providing information about these traits and taking action in their capacity as veterinarian. Articles 36 and 55 of the Dutch GWWD (animal health and welfare law) provide opportunities to act against the breeding of dogs with exaggerated genetic traits.

  18. Familial anthropophobia in pointer dogs?

    PubMed

    Dykman, R A; Murphree, O D; Reese, W G

    1979-08-01

    This article assesses a dog model in terms of a proposed cross-species definition of phobia, the model referring to a strain of unstable dogs that has been produced by selection and inbreeding. The unstable dogs are contrasted with a strain of stable dogs. New findings are presented on approach and activity behavior toward three stimulus objects (man, another dog, and a sheet-covered chair) in a naturalistic setting. The fear response of unstable dogs to objects other than man habituates gradually, whereas the fear response to the sight of man is far more enduring, suggesting a relatively specific fear of man.

  19. 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.

  20. 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

  1. 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

  2. Prevalence of incidental thyroid nodules in ultrasound studies of dogs with hypercalcemia (2008-2013).

    PubMed

    Pollard, Rachel E; Bohannon, Laurie K; Feldman, Edward C

    2015-01-01

    Ultrasound is commonly used to evaluate the cervical region in dogs with hypercalcemia due to suspected hyperparathyroidism. Incidental thyroid nodules may be detected during these studies, however little information has been published to guide clinical decision-making when this occurs. The purpose of this cross-sectional study was to determine the prevalence of incidental thyroid nodules in hypercalcemic dogs undergoing cervical ultrasound at our hospital during the period of 2008-2013. Dogs with a palpable neck mass were excluded. Cervical ultrasound images for each dog were retrieved and reviewed by a board certified veterinary radiologist who was unaware of patient outcome. Presence, number, and dimensions of thyroid nodules were recorded. Results of thyroid nodule aspirate, biopsy or necropsy were recorded from medical records when available. Ninety-one dogs met inclusion criteria. Of these, 14/91 (15%) dogs had at least one thyroid nodule. Mean (± standard deviation) thyroid gland nodule length, width, and height were 1.51 ± 0.74, 0.96 ± 0.73, and 0.75 ± 0.36 cm, respectively. A histologic diagnosis was available for the incidental thyroid lesions in eight dogs, including one dog with two nodules. Confirmed diagnoses for these nodules were thyroid cyst (3/9, 33%), thyroid adenoma (3/9, 33%), thyroid adenocarcinoma (2/9, 22%) and nodular hyperplasia (1/9, 11%). Findings indicated that incidental thyroid nodules may be present in hypercalcemic dogs with no palpable neck mass and no clinical signs of thyroid disease. Some of these nodules may be malignant and therefore a recommendation for cytology or biopsy may be justified.

  3. Aggressive digital papillary adenoma-adenocarcinoma.

    PubMed

    Keramidas, Evangelos G; Miller, Gavin; Revelos, Kyriakos; Kitsanta, Panagiota; Page, Robert E

    2006-01-01

    Aggressive digital papillary adenocarcinoma and aggressive digital papillary adenoma are rare tumours of the sweat glands. They are most common in the most distal part of the fingers and are locally aggressive with a 50% local recurrence rate; 14% of tumours metastasize. We present two cases.

  4. 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 ...

  5. Investigating the Role of FIP200 in Mammary Carcinogenesis Using a Transgenic Mouse Model

    DTIC Science & Technology

    2006-04-01

    in the mammary gland of virgin mice however, lactating mice have severe lobulo-alveolar hypoplasia in the mammary gland. 15. SUBJECT TERMS...mammary gland of virgin mice however, lactating mice have severe lobulo-alveolar hypoplasia in the mammary gland. Body Aim 1. Generation of mammary...leads to dwarfism and pregnant females have severe lobulo-alveolar hypoplasia affecting the mammary gland and, as a consequence, have difficulty

  6. Mouse mammary tumor virus suppresses apoptosis of mammary epithelial cells through ITAM-mediated signaling.

    PubMed

    Kim, Hyoung H; Grande, Shannon M; Monroe, John G; Ross, Susan R

    2012-12-01

    Many receptors in hematopoietic cells use a common signaling pathway that relies on a highly conserved immunoreceptor tyrosine-based activation motif (ITAM), which signals through Src family tyrosine kinases. ITAM-bearing proteins are also found in many oncogenic viruses, including the mouse mammary tumor virus (MMTV) envelope (Env). We previously showed that MMTV Env expression transformed normal mammary epithelial cells and that Src kinases were important mediators in this transformation. To study how ITAM signaling affects mammary cell transformation, we utilized mammary cell lines expressing two different ITAM-containing proteins, one encoding a MMTV provirus and the other a B cell receptor fusion protein. ITAM-expressing cells were resistant to both serum starvation- and chemotherapeutic drug-induced apoptosis, whereas cells transduced with these molecules bearing ITAM mutations were indistinguishable from untransduced cells in their sensitivity to these treatments. We also found that Src kinase was activated in the MMTV-expressing cells and that MMTV-induced apoptosis resistance was completely restored by the Src inhibitor PP2. In vivo, MMTV infection delayed involution-induced apoptosis in the mouse mammary gland. Our results show that MMTV suppresses apoptosis through ITAM-mediated Src tyrosine kinase signaling. These studies could lead to the development of effective treatment of nonhematopoietic cell cancers in which ITAM-mediated signaling plays a role.

  7. 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.

  8. DOG1 (clone K9) is seldom expressed and not useful in the evaluation of pancreatic neoplasms.

    PubMed

    Hemminger, Jessica; Marsh, William L; Iwenofu, Obiajulu Hans; Frankel, Wendy L

    2012-07-01

    DOG1, a transmembrane calcium-regulated chloride channel protein, is a sensitive and specific marker for gastrointestinal stromal tumors compared with other spindle cell and epithelioid neoplasms. Overexpression has also been described in a variety of both benign and malignant epithelial neoplasms. Recently, DOG1 immunoreactivity has been reported in pancreatic solid pseudopapillary tumors (SPT), suggesting a role as a marker for SPT. Utilizing immunohistochemistry, we evaluated DOG1 expression in pancreatic neoplasms to determine the prevalence of staining and establish diagnostic utility. Multiple tissue microarrays (TMA) were created from cores of formalin-fixed paraffin-embedded blocks containing pancreatic adenocarcinomas (n=112), neuroendocrine tumors (n=99), serous cystadenomas (n=28), and SPT (n=14) as well as normal pancreas (n=12). Immunoreactivity for DOG1 (clone K9) was assessed for intensity (1 to 3+), percentage of tumor positivity and location. Of the 99 cases of neuroendocrine tumors, only 2 (2%) were focally positive. Patchy staining was identified in 8 cases (7%) of adenocarcinoma of 1 to 2+ intensity, involving 15% to 80% of the tumor cells and primarily seen in a membranous and luminal distribution. In contrast to a previous report, no DOG1 positivity was observed in SPT, evaluated by both TMA and full sections. The TMAs of serous cystadenomas and normal pancreas were negative for DOG1. Rarely, pancreatic islets displayed granular, cytoplasmic staining. DOG1 antibody clone K9 is not a useful marker for SPT or other primary pancreatic neoplasms. Additional studies may be helpful to evaluate differences between clones of DOG1.

  9. Genetic Susceptibility to Estrogen-Induced Mammary Cancers

    DTIC Science & Technology

    2000-11-01

    mammary glands were reflected in mammary histology. (A and E) Thin sections from Fig. 3. E2 induced pituitary growth and hyperprolactinemia similarly in...with E2 5 (33%) exhibited a normal DNA profile where the great for 12 wk induced pituitary growth and hyperprolactinemia in majority of cells displayed...etal. , " terone, or PRL. Hyperprolactinemia has been shown to be sufficient to induce mammary cancer in certain strains of mouse 1 , (29-31) and rat

  10. 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.

  11. USF-1 as an Inhibitor of Mammary Gland Carcinogenesis

    DTIC Science & Technology

    2001-09-01

    The hypothesis tested in this proposal is that overexpression of USF in the mammary glands of transgenic mice will inhibit myc-dependent...tumorigenesis. To test this hypothesis, a transgene was constructed to target the overexpression of FLAG-tagged USF-2 to the mammary glands of transgenic mice ...under the control of the mouse mammary tumor virus (mmtv) long terminal repeat. A total of eight lines of transgenic mice were generated. Of these, one

  12. Paget cells in the esophagus: assessment of their histopathologic features and near-universal association with underlying esophageal adenocarcinoma.

    PubMed

    Abraham, Susan C; Wang, Huamin; Wang, Kenneth K; Wu, Tsung-Teh

    2008-07-01

    (complete loss in 1 and faint expression in 3, 57%). Overall, PAS-D was the most efficacious stain for highlighting Paget cells. A control group of 19 adenocarcinomas without Paget cells were also stained for E-cadherin; only 1 showed faint expression (5%) and none showed complete loss (P=0.01). These results demonstrate a low but significant prevalence (4.9%) of Paget cells in esophageal and esophagogastric junction adenocarcinomas. Unlike previously described cases of mammary, vulvar, and perianal Paget disease, esophageal Paget cells are almost universally associated with underlying adenocarcinoma and not with high grade dysplasia ("in situ" disease) or primary Paget disease. A commonality among cases with Paget cells is the presence of focal or diffuse, poorly differentiated adenocarcinoma with discohesive cells. E-cadherin alterations seem to play a less significant role.

  13. Establishment of mammary gland model in vitro: culture and evaluation of a yak mammary epithelial cell line.

    PubMed

    Fu, Mei; Chen, Yabing; Xiong, Xianrong; Lan, Daoliang; Li, Jian

    2014-01-01

    This study aimed to establish yak mammary epithelial cells (YMECs) for an in vitro model of yak mammary gland biology. The primary culture of YMECs was obtained from mammary gland tissues of lactating yak and then characterized using immunocytochemistry, RT-PCR, and western blot analysis. Whether foreign genes could be transfected into the YMECs were examined by transfecting the EGFP gene into the cells. Finally, the effect of Staphylococcus aureus infection on YMECs was determined. The established YMECs retained the mammary epithelial cell characteristics. A spontaneously immortalized yak mammary epithelial cell line was established and could be continuously subcultured for more than 60 passages without senescence. The EGFP gene was successfully transferred into the YMECs, and the transfected cells could be maintained for a long duration in the culture by continuous subculturing. The cells expressed more antimicrobial peptides upon S.aureus invasion. Therefore, the established cell line could be considered a model system to understand yak mammary gland biology.

  14. Bovine mammary stem cells: new perspective for dairy science.

    PubMed

    Martignani, E; Cravero, D; Miretti, S; Accornero, P; Baratta, M

    2014-01-01

    Mammary stem cells provide opportunities for the cyclic remodelling of the bovine mammary gland. Therefore, understanding the character and regulation of mammary stem cells is important for increasing animal health and productivity. The exciting possibility that stem cell expansion can influence milk production is currently being investigated by several researchers. In fact, appropriate regulation of mammary stem cells could hopefully benefit milk yield, persistency of lactation, dry period management and tissue repair. Accordingly, we and others have attempted to characterize and regulate the function of bovine mammary stem cells. However, research on mammary stem cells requires tissue biopsies, which represents a limitation for the management of animal welfare. Interestingly, different studies recently reported the identification of putative mammary stem cells in human breast milk. The possible identification of primitive cell types within cow's milk may provide a non-invasive source of relevant mammary cells for a wide range of applications. In this review, we have summarized the main achievements in this field for dairy cow science and described the interesting perspectives open to manipulate milk persistency during lactation and to cope with oxidative stress during the transition period by regulating mammary stem cells.

  15. Growth requirements of human mammary epithelial cells in culture.

    PubMed

    Taylor-Papadimitriou, J; Shearer, M; Stoker, M G

    1977-12-15

    Colony-forming epithelial cells can be separated from the non-dividing "foam cells" in human milk by differential adhesion to glass and freezing. The growth of such partially purified mammary epithelial cells is stimulated by co-culture with non-dividing feeder cells. Foam cells, mitomycin-treated mouse fibroblast lines and human mammary fibroblasts and calf lens epithelial cells are all effective in promoting mammary epithelial cell growth. Contact between epithelial cells and feeders is not required for the growth-promoting effect. The mitogenic effect of epidermal growth factor on mammary epithelial cells also requires feeder cell activity.

  16. Feline Mammary Carcinoma: A Retrospective Evaluation of 17 Cases

    PubMed Central

    Tomlinson, M. J.; Barteaux, L.; Ferns, L. E.; Angelopoulos, E.

    1984-01-01

    Seventeen biopsies of feline mammary carcinoma submitted to the Veterinary Pathology Laboratory, Nova Scotia Department of Agriculture and Marketing were reviewed. All 17 cases were female cats. Data on age, reproductive status (sexually intact vs. neutered), therapy, outcome of the cases and histological features were consistent with data on feline mammary carcinoma previously reported. Four of these 17 cats had a history of receiving exogenous progestin prior to tumor development. The possible role of progestins as initiators or promoters of feline mammary carcinoma was discussed. The use of feline mammary carcinoma as a model for carcinoma of the breast in women was reviewed. ImagesFigure 1. PMID:17422482

  17. Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis.

    PubMed

    Visvader, Jane E

    2009-11-15

    The epithelium of the mammary gland exists in a highly dynamic state, undergoing dramatic morphogenetic changes during puberty, pregnancy, lactation, and regression. The recent identification of stem and progenitor populations in mouse and human mammary tissue has provided evidence that the mammary epithelium is organized in a hierarchical manner. Characterization of these normal epithelial subtypes is an important step toward understanding which cells are predisposed to oncogenesis. This review summarizes progress in the field toward defining constituent cells and key molecular regulators of the mammary epithelial hierarchy. Potential relationships between normal epithelial populations and breast tumor subtypes are discussed, with implications for understanding the cellular etiology underpinning breast tumor heterogeneity.

  18. Apples prevent mammary tumors in rats.

    PubMed

    Liu, Rui Hai; Liu, Jiaren; Chen, Bingqing

    2005-03-23

    Regular consumption of fruits and vegetables has been consistently shown to be associated with reduced risk of developing chronic diseases such as cancer and cardiovascular disease. Apples are commonly consumed and are the major contributors of phytochemicals in human diets. It was previously reported that apple extracts exhibit strong antioxidant and antiproliferative activities and that the major part of total antioxidant activity is from the combination of phytochemicals. Phytochemicals, including phenolics and flavonoids, are suggested to be the bioactive compounds contributing to the health benefits of apples. Here it is shown that whole apple extracts prevent mammary cancer in a rat model in a dose-dependent manner at doses comparable to human consumption of one, three, and six apples a day. This study demonstrated that whole apple extracts effectively inhibited mammary cancer growth in the rat model; thus, consumption of apples may be an effective strategy for cancer protection.

  19. Cytokine signalling in mammary gland development.

    PubMed

    Watson, Christine J; Oliver, Carrie H; Khaled, Walid T

    2011-03-01

    Mammary gland development occurs in three distinct stages during the lifetime of the female mammal: in embryonic, pubertal and reproductive life. At each of these developmental stages, different signalling molecules induce changes in both the epithelium and the surrounding stroma. However, it is during pregnancy that the most dramatic changes occur, resulting in a massive increase in the number of epithelial cells and in their function. Pregnancy initiates the development of a new epithelial lineage, the alveolar cells, which form the milk-producing lobuloalveolar structures. These cells become redundant at the end of lactation and are removed in an exquisitely controlled process of tissue remodelling coupled with extensive cell death. All of these events require not only steroid hormones but also sequential signalling by cytokines. A recent surprising discovery was that the signalling pathways and cytokines that regulate lineage determination in T helper cells are also involved in mammary gland development during pregnancy.

  20. The evolving role of mammary ductoscopy.

    PubMed

    Mokbel, Kefah; Elkak, Abd Elrafea

    2002-01-01

    Mammary ductoscopy (MD) is an emerging technique that allows direct visualisation of the mammary duct system, and that produces sharp and clear video images and ductal washings for cytological analysis. There is a growing body of evidence that MD may have a role in the management of women with pathological nipple discharge, the guiding of breast conserving surgery for cancer, and the screening of high risk women. Further research is required to confirm these potential applications and the feasibility of its use in the rapid intervention and outpatient setting under local anaesthesia. Furthermore, the addition of molecular and genetic analysis of cells obtained by MD and the emergence of newer generations of microendoscopes are likely to enhance the use of this technique.

  1. 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…

  2. [Secret excretion from the mouse mammary gland].

    PubMed

    Tolkunov, Iu A; Balakina, G B; Markov, A G

    2000-02-01

    Histological studies revealed that the mammary gland nipple have smooth muscle fibres along the nipple channel. These fibres infiltrate the connective tissue parallel to the skin. The ring muscles are not obvious. Delays in the milk excretion in mice may be due to specifics of allocation and functioning of the nipple smooth muscles. To obtain milk, a mechanical action upon the nipple and a synchronised release of oxitocin into the blood are necessary.

  3. Leukocytes in Mammary Development and Cancer

    PubMed Central

    Coussens, Lisa M.; Pollard, Jeffrey W.

    2011-01-01

    Leukocytes, of both the innate and adaptive lineages, are normal cellular components of all tissues. These important cells not only are critical for regulating normal tissue homeostasis, but also are significant paracrine regulators of all physiologic and pathologic tissue repair processes. This article summarizes recent insights regarding the trophic roles of leukocytes at each stage of mammary gland development and during cancer development, with a focus on Murids and humans. PMID:21123394

  4. Characterization of Human Mammary Epithelial Stem Cells

    DTIC Science & Technology

    2007-10-01

    robust and reproducible methodology to detect, quantify and isolate stem cells in normal human mammary tissue, using a xenotransplantation system...covers the first year of the grant, during which substantial progress has been made in the development and validation of the xenotransplantation assay...Subrenal xenotransplantation surgery. The hair on the back of anesthetized mice was shaved, and the skin swabbed with 70% alcohol. An anterior to

  5. MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma.

    PubMed

    Schultz, Nicolai A; Werner, Jens; Willenbrock, Hanni; Roslind, Anne; Giese, Nathalia; Horn, Thomas; Wøjdemann, Morten; Johansen, Julia S

    2012-12-01

    MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P=2.06 × 10(-54)) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from non-neoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic

  6. 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.

  7. Mammary ductoscopy: past, present, and future.

    PubMed

    Pereira, Bernadette; Mokbel, Kefah

    2005-04-01

    Mammary ductoscopy (MD) allows direct visual access to the mammary ducts, using fiberoptic microendoscopes inserted through the ductal opening onto the nipple surface. Therefore it has a potential role in the diagnosis and treatment of intraductal breast disease. This article describes the anatomy of the mammary ductal system, the early beginnings of MD, its ongoing evolution, and the need for further development for its future usage in increasing clinical indications. MD is a useful diagnostic adjunct in patients with pathological nipple discharge (PND) and can guide duct excision surgery. However, its potential use in the early detection of breast cancer, in guiding breast-conserving surgery (BCS) for cancer, and in the therapeutic ablation of intraductal disease, as well as in guiding risk-reducing strategies among high-risk women, requires further research and evaluation. The development of a biopsy kit that obtains adequate microbiopsy samples for histological diagnosis under direct visualization will enhance the use of this technique by breast surgeons and radiologists. Future developments also include combining MD with molecular diagnostic markers and optical biopsy systems for the diagnosis of premalignant and early malignant disease, and combining MD with radiofrequency for curative ablation of intraductal lesions.

  8. Mammary ductoscopy: current issues and perspectives.

    PubMed

    Uchida, Ken; Fukushima, Hisaki; Toriumi, Yasuo; Kawase, Kazumi; Tabei, Isao; Yamashita, Akinori; Nogi, Hiroko

    2009-01-01

    Until recently, the mammary duct had not been directly observed in vivo. Starting with the success of Teboul et al., studies of mammary ductoscopy (MD) for nipple discharge have been performed in Japan and other East Asian countries. Ductal lavage screening trials for breast cancer started in the 2000s. Concurrently, the number of English-language articles about MD increased. Sixty-nine English-language and 74 Japanese-language papers published in the last 19 years were reviewed. Important reports and studies were analyzed. MD has undergone significant technological development, and studies of MD have taken place in many countries. As a result, endoscopic images of the mammary duct have developed, and the endoscopic diagnosis for nipple discharge has become possible. MD-guided biopsy and surgery have been studied. Findings of MD are useful for diagnosing intraductal lesions with nipple discharge. As a result, MD has reduced the number and extent of microdochectomies. MD is also helpful in guiding breast-conserving surgery. Many pioneers have tried direct biopsy or interventions under MD, but further developments are necessary for its practical use.

  9. Dogs, zoonoses and immunosuppression.

    PubMed

    Robinson, R A; Pugh, R N

    2002-06-01

    Dogs are the source of a wide range of zoonotic infections that pose a significant threat to human health. This is particularly the case for immunocompromised people, although there are few robust studies that determine immunosuppression as a risk factor for transmission of zoonoses from dogs to humans. An increasing proportion of human society is immunodeficient, principally through the advent of HIV infection and through more people, particularly the expanding elderly group, being subjected to immunosuppressive agents. This is happening at a time when more such people are capitalizing on the acknowledged benefits of dog ownership, making for a potentially dangerous mix. Enteric pathogens (for example, Salmonella, Campylobacter and Cryptosporidium species, that may be canine derived) are a frequent risk to the health of immunocompromised persons. Veterinarians and physicians can be criticised for not communicating with each other, and for not providing adequate risk assessment to pet owners. There is scope for voluntary groups to provide information and support for the immunosuppressed who wish to keep their dogs. Key recommendations are to maintain a clean personal environment and intact mucocutaneous barriers. Public health professionals could help rectify the current communications gap between veterinary and medical staff and so facilitate in the appropriate management of dog-owning immunocompromised people.

  10. Mammary extracellular matrix directs differentiation of testicular and embryonic stem cells to form functional mammary glands in vivo

    PubMed Central

    Bruno, Robert D.; Fleming, Jodie M.; George, Andrea L.; Boulanger, Corinne A.; Schedin, Pepper; Smith, Gilbert H.

    2017-01-01

    Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived cells to produce normal mammary epithelial trees within epithelial divested mouse mammary fat-pads. Conversely, ECMs isolated from omental fat and lung did not redirect testicular cells to a MEC fate, indicating the necessity of tissue specific components of the mECM. mECM preparations also completely inhibited teratoma formation from ESC inoculations. Further, a phenotypically normal ductal outgrowth resulted from a single inoculation of ESCs and mECM. To the best of our knowledge, this is the first demonstration of a tissue specific ECM driving differentiation of cells to form a functional tissue in vivo. PMID:28071703

  11. Technical note: Mammary gland ultrasonography to evaluate mammary parenchymal composition in prepubertal heifers.

    PubMed

    Albino, R L; Guimarães, S E F; Daniels, K M; Fontes, M M S; Machado, A F; Dos Santos, G B; Marcondes, M I

    2017-02-01

    Bovine mammary gland development studies are often terminal or involve invasive biopsy procedures. Therefore, noninvasive means of assessing mammary development should be considered as alternative methods in live animals. The objective was to test if mammary ultrasonography can be used as a noninvasive way to estimate mammary parenchyma (PAR) composition in prepubertal dairy heifers with different average daily body weight gains. In the 84 d preceding, the ultrasound exam heifers were maintained in 1 of 3 treatment groups. Individual heifers were fed a high gain (1 kg/d; n = 6), low gain (0.5 kg/d, n = 6), or maintenance (n = 6) treatment diet. To achieve desired body weight gains, heifers were fed differing amounts of the same silage-based diet. Mammary glands of 18 crossbred heifers Holstein:Gyr underwent a single mammary ultrasound exam immediately before heifer slaughter, which took place when heifers weighed 142.0 ± 8.0 kg and were 200 d old. The 4 mammary glands of each heifer were evaluated using a real-time B-mode ultrasound machine equipped with a 6.5-MHz micro-convex transducer. Digital images (8-bit) of glands were obtained and PAR was identified within gland. Average pixel values per unit of PAR area were determined for each gland and analyzed at the level of heifer. Pixel results were interpreted on the basis that lower average pixel values reflect PAR with relatively high amounts of protein as opposed to fat. To help validate that the pixel value within PAR is associated with composition of PAR, pixel findings were compared with histological [number of adipocytes in PAR (Nad) and epithelial area in PAR (Ep)] and biochemical [percent crude protein in PAR (%CP), percent ether extract in PAR (%EE), PAR weight (WPAR), and mammary fat pad weight (WFAT)] composition of PAR in these same heifers. Within PAR, %EE and WFAT were positively correlated with pixel values, whereas %CP, Ep, and Nad were negatively correlated. Parenchyma weight did not correlate

  12. Bartonella quintana Endocarditis in Dogs

    PubMed Central

    Rolain, Jean-Marc; Maggi, Ricardo; Sontakke, Sushama; Keene, Bruce; Hunter, Stuart; Lepidi, Hubert; Breitschwerdt, Kyle T.; Breitschwerdt, Edward B.; Raoult, Didier

    2006-01-01

    We provide the first evidence that Bartonella quintana can infect dogs and cause typical signs of endocarditis. Using PCR and sequencing, we identified B. quintana in the blood of a dog from the United States with aortic valve endocarditis and probably also in the mitral valve of a dog from New Zealand with endocarditis. PMID:17326937

  13. 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...

  14. Keratin 6 is not essential for mammary gland development

    PubMed Central

    Grimm, Sandra L; Bu, Wen; Longley, Mary Ann; Roop, Dennis R; Li, Yi; Rosen, Jeffrey M

    2006-01-01

    Introduction Keratin 6 (K6) has previously been identified as a marker of early mammary gland development and has also been proposed to be a marker of mammary gland progenitor cells. However, the function of K6 in the mammary gland was not known, so we examined the expression pattern of the protein during both embryonic and postnatal mammary development, as well as the mammary gland phenotype of mice that were null for both K6a and K6b isoforms. Method Immunostaining was performed to determine the expression pattern of K6a throughout mammary gland development, from the embryonic mammary bud to lactation. Double immunofluorescence was used to co-localize K6 with known markers of mammary gland development. Wild-type and K6ab-null mammary tissues were transplanted into the cleared fat pads of nude mice and the outgrowths were analyzed for morphology by whole-mount staining and for markers of mammary epithelium by immunostaining. Finally, progesterone receptor (PR) and bromodeoxyuridine co-localization was quantified by double immunofluorescence in wild-type and K6ab-null mammary outgrowths. Results Here we report that K6 is expressed earlier than described previously, by embryonic day 16.5. K6a is the predominant isoform expressed in the mammary gland, localized in the body cells and luminal epithelial cells but not in the cap cells or myoepithelial cells. Co-localization studies showed that most K6a-positive cells express steroid receptors but do not proliferate. When both the K6a and K6b genes are deleted, mammary gland development appears normal, with similar expression of most molecular markers examined in both the pubertal gland and the mature gland. Loss of K6a and K6b, however, leads to an increase in the number of steroid-receptor-positive cells, and increased co-localization of steroid receptor expression and proliferation was observed. Conclusion Although K6a was not essential for mammary gland development, loss of both K6a and K6b resulted in an increase in

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

    ClinicalTrials.gov

    2016-09-15

    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

  16. Crohn enteritis-associated small bowel adenocarcinomas exhibit gastric differentiation.

    PubMed

    Whitcomb, Emma; Liu, Xiuli; Xiao, Shu-Yuan

    2014-02-01

    Primary small bowel adenocarcinoma is rare. Although generally similar to colonic adenocarcinoma, some small bowel adenocarcinomas exhibit unique morphologic features, particularly those arising in association with Crohn disease. In this study, 15 sporadic small bowel adenocarcinomas and 11 Crohn enteritis-associated small bowel adenocarcinomas were examined for histology and immunohistochemical profile including cytokeratins (CK) 7 and 20, intestinal markers CDX2 and MUC2, and gastric epithelial markers MUC5AC and MUC6. We found that Crohn enteritis-associated small bowel adenocarcinomas frequently resemble gastric tubular adenocarcinoma histologically. In addition, when compared to sporadic small bowel adenocarcinoma, the former expressed MUC5AC and MUC6 with much higher frequency (82% vs. 7% and 73% vs. 0%, respectively). Ten of 11 Crohn enteritis-associated small bowel adenocarcinomas (91%) were positive for at least one gastric-type marker (MUC5AC or MUC6). Expression of CK7 was also more frequent in Crohn enteritis-associated small bowel adenocarcinoma (73% versus 27%) while expression of CK20 was less frequent (64% vs. 100%). There was no difference between sporadic and Crohn enteritis-associated small bowel adenocarcinoma in expression of CDX2 (100% vs. 91%) and MUC2 (93% vs. 73%). These observations suggest that there is a difference in the morphologic and immunohistochemical characteristics of sporadic versus Crohn enteritis-associated small bowel adenocarcinoma, particularly in their expression of gastric-type mucin. The findings also suggest that gastric differentiation in Crohn enteritis-associated small bowel adenocarcinoma is related to gastric metaplasia, a common phenomenon in Crohn disease.

  17. Clinical staging in bitches with mammary tumors: Influence of type and histological grade

    PubMed Central

    Gundim, Lígia F.; de Araújo, Camila P.; Blanca, William T.; Guimarães, Ednaldo C.; Medeiros, Alessandra A.

    2016-01-01

    Breast tumors are the most common tumors in dogs and the study of disease prognostic factors is important for establishing the appropriate treatment protocols. The purpose of this study was to clinically stage mammary tumors of bitches and correlate the stages with histological type and grade. The tumors of 63 dogs were clinically staged based on the findings of tumor sizing, lymph node evaluation, and radiographic examination. After surgical excision, the tumors were classified histologically and graded. The relationship between the tumor grade, stage, and histological type was evaluated using a binomial test. Stage I tumors were the most numerous (31.75%), followed by tumors at stages II, III, IV, and V. Animals with histological grade I carcinomas presented stage I, II, or III tumors more frequently and stage IV and V tumors less frequently. The number of animals with simple carcinomas that were at stage I of the disease was greater than that at stage V. Carcinomas in the mixed tumors were less aggressive; however, the small number of animals in stage V of the disease made any statistical association impossible. The complex carcinomas presented with the invasion of the lymph nodes and less cellular differentiation in a larger number of animals than did simple carcinomas. Histological grading proved to be the best parameter for the prognostic evaluation of the breast carcinomas. PMID:27733787

  18. Directionality of dog vocalizations

    NASA Astrophysics Data System (ADS)

    Frommolt, Karl-Heinz; Gebler, Alban

    2004-07-01

    The directionality patterns of sound emission in domestic dogs were measured in an anechoic environment using a microphone array. Mainly long-distance signals from four dogs were investigated. The radiation pattern of the signals differed clearly from an omnidirectional one with average differences in sound-pressure level between the frontal and rear position of 3-7 dB depending from the individual. Frequency dependence of directionality was shown for the range from 250 to 3200 Hz. The results indicate that when studying acoustic communication in mammals, more attention should be paid to the directionality pattern of sound emission.

  19. Pancreatic Adenocarcinoma, Version 2.2012

    PubMed Central

    Tempero, Margaret A.; Arnoletti, J. Pablo; Behrman, Stephen W.; Ben-Josef, Edgar; Benson, Al B.; Casper, Ephraim S.; Cohen, Steven J.; Czito, Brian; Ellenhorn, Joshua D. I.; Hawkins, William G.; Herman, Joseph; Hoffman, John P.; Ko, Andrew; Komanduri, Srinadh; Koong, Albert; Ma, Wen Wee; Malafa, Mokenge P.; Merchant, Nipun B.; Mulvihill, Sean J.; Muscarella, Peter; Nakakura, Eric K.; Obando, Jorge; Pitman, Martha B.; Sasson, Aaron R.; Tally, Anitra; Thayer, Sarah P.; Whiting, Samuel; Wolff, Robert A.; Wolpin, Brian M.; Freedman-Cass, Deborah A.; Shead, Dorothy A.

    2013-01-01

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting. PMID:22679115

  20. Prolactin, TNF alpha and nitric oxide expression in nitroso-N-methylurea-induced-mammary tumours

    PubMed Central

    Vegh, Irene; de Salamanca, Rafael Enríquez

    2007-01-01

    Background The N-Nitrosomethylurea breast cancer model induced in rats is used for the study of carcinogenesis in mammary cancer, prostate, pancreas, etc. This model is very similar to human neoplastic disease. Methods The present experimental study was designed to assess whether metoclopramide administration has any effect on development of MNU-induced tumours, and evaluate the treatment of goserelin acetate on PRL, TNF alpha and NO expression. NMU was administered to female Wistar rats on 2 occasions (5 mg/100 g body w/rat). PRL and TNF alpha were performed by immune-assay. Nitric Oxide by semi automated-assay and ploidy analyses by flow cytometry. Results The administration of metoclopramide made the induction time shorter and increased the incidence and average of tumours per rat. Tumours development was inhibited by a goserelin chronic administration. The ploidy of adenocarcinoma was polyploid-aneuploid type (average S = 60%). It was higher basal PRL plasma levels in rats with NMU induced tumours than in basal controls without tumour (p < 0.001). The goserelin "in bolus" administration showed maximal inhibition of plasma PRL at 90 min. Plasmatic TNF alpha expression was inhibited at 60 min and also remained inhibited in tissue homogenate post chronic treatment (P < 0.0125). Plasmatic NO expression is higher in rats with induced tumours than healthy controls (P < 0.001). In tissue homogenate NO values were inhibited at 90 min (P < 0.01), as well during chronically goserelin treatment (P < 0.005). Conclusion The increase of blood PRL levels in NMU-induced rats may be an indicator of a poor prognosis of mammary cancer evolution. The metoclopramide administration accelerates tumour growth. However goserelin administration achieves regression in tumour development associated to inhibition PRL, TNF alpha and NO expression. PMID:18045456

  1. Identification of rat mammary tumor-1 gene (RMT-1), which is highly expressed in rat mammary tumors.

    PubMed

    Chiou, S; Yoo, J; Loh, K C; Guzman, R C; Gopinath, G R; Rajkumar, L; Chou, Y C; Yang, J; Popescu, N C; Nandi, S

    2001-12-10

    Full-term pregnancy early in life results in a permanent reduction in lifetime breast cancer risk in women. Parous rats and mice are also refractory to chemical carcinogenesis. Therefore, investigation of the differences between mammary glands from virgin and parous rats would provide valuable information regarding the protective effects of early full-term pregnancy. In this report, we examined the gene expression patterns in mammary glands from virgin and parous Lewis rats. Using differential display technology, a novel 4.2 kb cDNA, designated rat mammary tumor-1 (RMT-1) was isolated. Northern blot analysis of RMT-1 showed that RMT-1 expression was higher in the pre-pubertal and pubertal stages during rat mammary gland development while it was down-regulated in mammary glands from mature virgin and parous rats. RMT-1 expression was highest in rat mammary cancers compared with either the mammary glands of virgin or parous rats. At the Northern blot sensitivity level, RMT-1 expression was found only in the mammary gland. Northern blot analysis also showed that the expression of this gene was found in 74% of N-methyl-nitrosourea (MNU)-induced mammary cancers while it was not found in MNU-induced cancers from other organs. The examination of the RMT-1 gene structure revealed that it consists of five exons spanning 5.9 kb. Using fluorescence in situ hybridization, the gene was localized on rat chromosome 1 band q 43-51. The present data show that there is a correlation between high RMT-1 expression and rat mammary carcinogenesis or decreased RMT-1 expression and parity associated refractoriness to chemically induced mammary carcinogenesis. However, whether or not RMT-1 gene has a functional role in these processes remains to be investigated.

  2. Insertion mutation of the int-1 and int-2 loci by mouse mammary tumor virus in premalignant and malignant neoplasms from the GR mouse strain.

    PubMed Central

    Morris, D W; Barry, P A; Bradshaw, H D; Cardiff, R D

    1990-01-01

    Mouse mammary tumor virus (MMTV)-induced mammary adenocarcinomas can develop from several different premalignant precursors common in GR mice. Insertion mutagenesis of the mammary protooncogenes int-1 and int-2 was studied in this multistep system by analyzing samples from various stages of neoplastic development for novel int-1 and int-2 restriction fragments generated by MMTV provirus integration. int-1 and int-2 insertion mutations were observed in both premalignant lesions and malignant tumors. Some of the tumors with insertion mutations were experimentally derived from insertion mutation-free premalignant precursors. Each class of neoplasm examined had a characteristic frequency of int-1 and int-2 insertion mutations; however, no correspondence was observed between neoplasm morphology and mutation of either gene. These results indicate that insertion mutation of the int-1 and int-2 loci by MMTV provirus can be involved in the earliest identifiable stages of neoplastic development as well as during progression of premalignant lesions to tumors. Insertion mutation of int-1 and int-2 is therefore not stage specific in this system. Images PMID:2157060

  3. 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 ...

  4. Traumatic pseudoaneurysm of left internal mammary artery graft.

    PubMed

    Agathos, E A; Hussein, A; Trehan, H; Trenholme, S E; Floten, H S

    1993-10-01

    Traumatic pseudoaneurysm of the left internal mammary artery was recognized as a possible causal factor in the early recurrence of angina in a 51-year-old man. This patient underwent reoperation for revascularization with the left internal mammary artery graft in situ.

  5. 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

  6. The Krakatau syndrome; a late complication of retroglandular mammary augmentation.

    PubMed

    Vuursteen, P J

    1992-01-01

    A late complication of retroglandular mammary augmentation is described, in which severe fibrous capsular contraction with calcification of the capsule causes pressure atrophy of the centre of the mammary gland and sometimes even atrophy of the underlying pectoralis major muscle. The complication was observed in six patients. Two representative cases are described and the treatment is discussed.

  7. P-Cadherin Expression in Feline Mammary Tissues

    PubMed Central

    Figueira, Ana Catarina; Teodósio, Ana Sofia; Carvalheira, Júlio; Lacerda, Manuela; de Matos, Augusto; Gärtner, Fátima

    2012-01-01

    The search for molecular markers in the feline mammary gland, namely, the adhesion molecules belonging to the cadherin family, is useful in the understanding of the development of mammary carcinomas in felines and humans. To study P-cadherin expression in the feline mammary gland, 61 samples of normal (n = 4), hyperplastic (n = 12), and neoplastic (n = 45) feline mammary tissues were examined. In both normal and hyperplastic mammary tissues as well as in benign tumours, P-cadherin immunolabelling was restricted to myoepithelial cells. In malignant tumours, however, there was an aberrant epithelial P-cadherin immunoexpression in 64.1% (n = 25) of cases, with a membranous and/or cytoplasmic pattern of distribution. A statistically significant relationship was seen between epithelial P-cadherin expression and malignant mammary lesions (P = 0.0001). In malignant mammary tumours, there was likewise a statistically significant relationship between aberrant P-cadherin immunoexpression and histological grade (P = 0.0132). Aberrant epithelial P-cadherin expression seems to be related to malignancy in the feline mammary gland. To confirm the results of this investigation, further studies with larger samples and follow-up studies are warranted. PMID:23091776

  8. 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.

  9. [Atypical metastatic site of lung adenocarcinoma].

    PubMed

    Sakhri, L; Mennecier, B; Jacqmin, D; Di Marco, A; Schumacher, C; Chenard, M-P; Bergmann, E; Quoix, E

    2011-12-01

    The case concerns a 40 years old smoker male, treated for an adenocarcinoma of the left upper lobe, metastatic in muscle extended to the right femur cortex. The patient had first a surgical excision of the mass of the thigh, an intramedullary femoral nailing, and six courses of chemotherapy (cisplatin-vinorelbine) with concurrent thoracic radiotherapy. This treatment led to disease stability. One year later, hematuria revealed a bladder tumor. Cystoscopy with biopsy concluded to an adenocarcinoma pulmonary origin. The PET-scanner showed an uptake of the bladder mass, a hypermetabolic right adrenal gland and subcutaneous left shoulder nodule. The patient had a partial cystectomy associated with enterocystoplasty and left ureteral reimplantation, plus excision of the subcutaneous nodule located in the left shoulder and a right adrenalectomy during the same time. All of the sites were metastasis from adenocarcinoma of pulmonary origin. A salvage chemotherapy was initiated. In the vast majority of cases, bladder metastasis as primary bladder tumours is revealed by hematuria, cystitis or sometimes vague pelvic pain. Our case is a very unusual bladder metastatic site from lung cancer. We will discuss the different procedures and the therapeutic strategies on the basis of the published data.

  10. Laparoscopy in the management of gastric adenocarcinoma.

    PubMed Central

    Burke, E C; Karpeh, M S; Conlon, K C; Brennan, M F

    1997-01-01

    OBJECTIVE: The authors determined the accuracy of laparoscopy in detecting metastatic disease in patients with gastric adenocarcinoma. SUMMARY BACKGROUND DATA: The majority of patients with gastric adenocarcinoma in the United States present with advanced disease. They are at high risk for intraabdominal metastatic spread. METHODS: One hundred eleven patients with gastric adenocarcinoma underwent laparoscopy at Memorial-Sloan Kettering Cancer Center from December 1991 to December 1995. All were judged to be free of intra-abdominal metastatic disease on preoperative computed tomographic scan imaging. RESULTS: Laparoscopic exploration was successful in 110 of 111 patients and accurately staged 94% of the patients with respect to metastatic disease with a sensitivity of 84% and a specificity of 100%. The prevalence rate of metastatic disease was 37%. Twenty-four patients underwent laparoscopy only and were discharged in an average 1.4 days versus 6.5 days in patients undergoing exploratory laparotomy without resection (p < 0.05). No patients undergoing laparoscopy only have returned for palliative surgery. CONCLUSIONS: Laparoscopy should be performed in nonobstructed, nonbleeding patients with advanced gastric cancer in the United States. More than one third of these patients have unsuspected metastatic disease at time of operation. Laparoscopy is highly accurate in detecting occult metastases and identifies a unique population of stage IV patients who may benefit from newer induction chemotherapeutic approaches while avoiding unnecessary laparotomy. Images Figure 4. PMID:9060581

  11. 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

  12. Intraoperative molecular imaging to identify lung adenocarcinomas

    PubMed Central

    Newton, Andrew D.; Kennedy, Gregory T.; Predina, Jarrod D.; Low, Philip S.

    2016-01-01

    Intraoperative molecular imaging is a promising new technology with numerous applications in lung cancer surgery. Accurate identification of small nodules and assessment of tumor margins are two challenges in pulmonary resections for cancer, particularly with increasing use of video-assisted thoracoscopic surgery (VATS). One potential solution to these problems is intraoperative use of a fluorescent contrast agent to improve detection of cancer cells. This technology requires both a targeted fluorescent dye that will selectively accumulate in cancer cells and a specialized imaging system to detect the cells. In several studies, we have shown that intraoperative imaging with indocyanine green (ICG) can be used to accurately identify indeterminate pulmonary nodules. The use of a folate-tagged fluorescent molecule targeted to the folate receptor-α (FRα) further improves the sensitivity and specificity of detecting lung adenocarcinomas. We have demonstrated this technology can be used as an “optical biopsy” to differentiate adenocarcinoma versus other histological subtypes of pulmonary nodules. This strategy has potential applications in assessing bronchial stump margins, identifying synchronous or metachronous lesions, and rapidly assessing lymph nodes for lung adenocarcinoma. PMID:28066672

  13. 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

  14. 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.

  15. 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

  16. Experimental parvovirus infection in dogs.

    PubMed Central

    Potgieter, L N; Jones, J B; Patton, C S; Webb-Martin, T A

    1981-01-01

    Five eight week old dogs were inoculated orally and intranasally with cell culture origin canine parvovirus. Three dogs became depressed and anorectic and developed a mild (one dog) to severe diarrhea five days postinfection. The remaining dogs had subclinical infections but developed a lymphopenia followed by a transient lymphocytosis. The ill dogs developed mild (one dog) to severe neutropenia and a moderate lymphopenia. One died nine days postinfection. Recovery was associated with cessation of viral excretion and with lymphocytosis and antibody production. Two of three dogs challenged intragastrically developed mild clinical signs and a moderate panleukopenia four to eight days postinfection. The pathological changes of the experimental disease were very similar to that of spontaneous disease. Bone marrow changes included a severe granulocytic and mild erythroid depletion. The pathogenesis of canine parvovirus infection is discussed. Images Fig. 4. Fig. 5. Fig. 6. PMID:7340906

  17. Lessons learned from cloning dogs.

    PubMed

    Kim, M J; Oh, H J; Kim, G A; Park, J E; Park, E J; Jang, G; Ra, J C; Kang, S K; Lee, B C

    2012-08-01

    The aim of this article is to review dog cloning research and to suggest its applications based on a discussion about the normality of cloned dogs. Somatic cell nuclear transfer was successfully used for production of viable cloned puppies despite limited understanding of in vitro dog embryo production. Cloned dogs have similar growth characteristics to those born from natural fertilization, with no evidence of serious adverse effects. The offspring of cloned dogs also have similar growth performance and health to those of naturally bred puppies. Therefore, cloning in domestic dogs can be applied as an assisted reproductive technique to conserve endangered species, to treat sterile canids or aged dogs, to improve reproductive performance of valuable individuals and to generate disease model animals.

  18. 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.

  19. Characterization of neutral TRH-like peptides in mammary gland, mammary tumors and milk.

    PubMed

    Ghilchik, M W; Tobaruela, M; del Rio-Garcia, J; Smyth, D G

    2000-06-01

    Three pyroglutamylpeptide amides, pGlu-Glu-Pro amide, pGlu-Phe-Pro amide and pGlu-Gln-Pro amide, with similar structures to thyrotropin-releasing hormone (TRH), have been identified previously in the male reproductive system. We report here that rat and human mammary gland contain neutral TRH-immunoreactive peptides which are not retained on cation or anion exchange chromatography and that similar peptides occur in the milk of rat, cow, ewe and sow. The TRH-like peptides in lyophilized milk from the cow were purified by gel exclusion chromatography, mini-column cation exchange chromatography and reversed phase high performance liquid chromatography (HPLC) and the chromatographed peptides were located by TRH radioimmunoassay (RIA). In each chromatographic system the major TRH-immunoreactive peptide from cow milk exhibited identical behavior to pGlu-Phe-Pro amide; in addition there were two minor TRH-immunoreactive components. The possible physiological role of the TRH-like peptides in the mammary gland is discussed. In a series of patients with breast carcinoma, mammary tumor tissue was shown to contain approximately four times more TRH-like peptide than normal mammary tissue from the same patient, raising the possibility that the TRH-like peptides may be implicated in tumor development.

  20. 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

  1. Mammary gland stem cells and their application in breast cancer.

    PubMed

    Yang, Xing; Wang, Hui; Jiao, Baowei

    2017-02-07

    The mammary gland is an organ comprising two primary lineages, specifically the inner luminal and the outer myoepithelial cell layers. Mammary gland stem cells (MaSCs) are highly dynamic and self-renewing, and can give rise to these mammary gland lineages. The lineages are responsible for gland generation during puberty as well as expansion during pregnancy. In recent years, researchers have focused on understanding how MaSCs are regulated during mammary gland development and transformation of breast cancer. Here, we summarize the identification of MaSCs, and how they are regulated by the signaling transduction pathways, mammary gland microenvironment, and non-coding RNAs (ncRNAs). Moreover, we debate the evidence for their serving as the origin of breast cancer, and discuss the therapeutic perspectives of targeting breast cancer stem cells (BCSCs). In conclusion, a better understanding of the key regulators of MaSCs is crucial for the clinical treatment of breast cancer.

  2. Proteomic analysis of microsomes from lactating bovine mammary gland.

    PubMed

    Peng, Lifeng; Rawson, Pisana; McLauchlan, Danyl; Lehnert, Klaus; Snell, Russell; Jordan, T William

    2008-04-01

    Mammary gland has multiple metabolic potential including for large-scale synthesis of milk proteins, carbohydrate, and lipids including nutrient triacylglycerols. We have carried out a proteomic analysis of mammary tissue to discover proteins that affect lipid metabolism. Unfractionated microsomes from lactating bovine mammary tissue were analyzed using one-dimensional SDS-PAGE with RPLC-ESI-MS/MS. This approach gave 703 proteins including 160 predicted transmembrane proteins. Proteins were classified according to their subcellular localizations and biological functions. Over 50 proteins were associated with cellular uptake, metabolism, and secretion of lipids, including some enzymes that have been previously associated with breast cancer and potential therapeutic targets. This database develops a proteomic view of the metabolic potential of mammary gland that can be expected to contribute to a greater understanding of gene expression and tissue remodeling associated with lactation, and to further dissection of normal and pathological processes in mammary tissue.

  3. Plk2 regulates mitotic spindle orientation and mammary gland development.

    PubMed

    Villegas, Elizabeth; Kabotyanski, Elena B; Shore, Amy N; Creighton, Chad J; Westbrook, Thomas F; Rosen, Jeffrey M

    2014-04-01

    Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here, we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and that this might account for its suggested role as a tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally, a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development.

  4. Luminal progenitors restrict their lineage potential during mammary gland development.

    PubMed

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-02-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

  5. Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development

    PubMed Central

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-01-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes. PMID:25688859

  6. Stem cells in normal mammary gland and breast cancer.

    PubMed

    Luo, Jie; Yin, Xin; Ma, Tao; Lu, Jun

    2010-04-01

    The mammary gland is a structurally dynamic organ that undergoes dramatic alterations with age, menstrual cycle, and reproductive status. Mammary gland stem cells, the minor cell population within the mature organ, are thought to have multiple functions in regulating mammary gland development, tissue maintenance, major growth, and structural remodeling. In addition, accumulative evidence suggests that breast cancers are initiated and maintained by a subpopulation of tumor cells with stem cell features (called cancer stem cells). A variety of methods have been developed to identify and characterize mammary stem cells, and several signal transduction pathways have been identified to be essential for the self-renewal and differentiation of mammary gland stem cells. Understanding the origin of breast cancer stem cells, their relationship to breast cancer development, and the differences between normal and cancer stem cells may lead to novel approaches to breast cancer diagnosis, prevention, and treatment.

  7. Mammary development and breast cancer: the role of stem cells.

    PubMed

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

    2011-06-01

    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.

  8. Is your dog empathic? Developing a Dog Emotional Reactivity Survey.

    PubMed

    Szánthó, Flóra; Miklósi, Ádám; Kubinyi, Enikő

    2017-01-01

    Dogs' seemingly empathic behaviour attracts general and scientific attention alike. Behaviour tests are usually not sufficiently realistic to evoke empathic-like behaviour; therefore we decided to ask owners about their experiences with their dogs in emotionally loaded situations. Owners from Hungary (N = 591) and from Germany (N = 2283) were asked to rate their level of agreement on a 1-5 Likert scale with statements about the reactivity of their dogs to their emotions and to other dogs' behaviour. We created two scales with satisfactory internal reliability: reactivity to the owner's emotion and reactivity to other dogs' behaviour. Based on an owner-dog personality matching theory, we hypothesised that the owner's empathy, as measured by the subscale on the cooperativeness character factor of the human personality, will correlate with their dog's emotional reactivity in emotionally loaded situations. In addition we also examined how anthropomorphism, contagious yawning, attitude toward the dog are related to emotional reactivity in dogs as perceived by the owner. In addition we examined how owners rate dog pictures. We found that the scale scores were largely independent from demographic and environmental variables like breed, sex, age, age at acquiring, keeping practices, training experiences and owner's age. However, anthropomorphic and emotional attitude of the owners probably biased the responses. In the German sample more empathic owners reported to have more emotionally reactive dog, as expected by the personality matching theory. More empathic owners reported to have fewer problems with their dogs and they rated a puppy picture as more cute in both countries. 62% of owners from Hungary and 36% of owner from Germany agreed with the statement "My dog is more important for me than any human being". In Germany, more empathic owners agreed less with this statement and indicated that their dogs have a tendency for contagious yawning. Owners whose attitudes

  9. The non-inflammatory role of C1q during Her2/neu-driven mammary carcinogenesis.

    PubMed

    Bandini, Silvio; Macagno, Marco; Hysi, Albana; Lanzardo, Stefania; Conti, Laura; Bello, Amanda; Riccardo, Federica; Ruiu, Roberto; Merighi, Irene Fiore; Forni, Guido; Iezzi, Manuela; Quaglino, Elena; Cavallo, Federica

    2016-01-01

    There is an ever increasing amount of evidence to support the hypothesis that complement C1q, the first component of the classical complement pathway, is involved in the regulation of cancer growth, in addition to its role in fighting infections. It has been demonstrated that C1q is expressed in the microenvironment of various types of human tumors, including breast adenocarcinomas. This study compares carcinogenesis progression in C1q deficient (neuT-C1KO) and C1q competent neuT mice in order to investigate the role of C1q in mammary carcinogenesis. Significantly accelerated autochthonous neu(+) carcinoma progression was paralleled by accelerated spontaneous lung metastases occurrence in C1q deficient mice. Surprisingly, this effect was not caused by differences in the tumor-infiltrating cells or in the activation of the complement classical pathway, since neuT-C1KO mice did not display a reduction in C3 fragment deposition at the tumor site. By contrast, a significant higher number of intratumor blood vessels and a decrease in the activation of the tumor suppressor WW domain containing oxidoreductase (WWOX) were observed in tumors from neuT-C1KO as compare with neuT mice. In parallel, an increase in Her2/neu expression was observed on the membrane of tumor cells. Taken together, our findings suggest that C1q plays a direct role both on halting tumor angiogenesis and on inducing apoptosis in mammary cancer cells by coordinating the signal transduction pathways linked to WWOX and, furthermore, highlight the role of C1q in mammary tumor immune surveillance regardless of complement system activation.

  10. Mammary carcinogenic effect of low-dose fission radiation in Wistar/Furth rats and its dependency on prolactin

    SciTech Connect

    Yokoro, K.; Sumi, C.; Ito, A.; Hamada, K.; Kanda, K.; Kobayashi, T.

    1980-06-01

    The mammary carcinogenic effect in rats of low-dose fission radiation and its dependency on prolactin were studied. A total of 141 female W/Fu rats were exposed to 4.8, 8.9, or 19.5 rads of fission radiation that had both fission neutrons of 2.0 million electron volts (MeV) and gamma ray components similar to those produced by the Hiroshima bomb. Only 1 of 48 rats (2.0%) developed mammary tumor (MT) after irradiation alone, whereas 20 of 48 rats (41.6%) developed MT's if prolactin was supplied shortly after irradiation by means of grafting of the prolactin-secreting pituitary tumor. Furthermore, MT's occurred in 11 of 45 rats (24.4%) treated wit prolactin as late as 12 months after irradiation, which suggested the long-term survival of radiation-induced dormant MT cells. A correlation was found between the development of MT and the elevation of serum prolactin level; most MT's appeared shortly after the grafted mammotropic pituitary tumor became palpable. The growth of MT's appeared to be promoted by prolactin in collaboration with ovarian hormones; the growth of adenocarcinomas was dependent on prolactin and ovarian hormones, whereas the growth of fibroadenomas appeared to be less hormone-dependent. Much higher bioiogic effectiveness, especially in the low-dose range, was found with 2.0-MeV fission neutrons compared with 14.1-MeV fast neutrons or 180-kilovolt peak X-rays in rat mammary carcinogenesis.

  11. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma

    PubMed Central

    2012-01-01

    Background Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. Case presentation A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. Conclusion We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders. PMID:22873795

  12. Differences in leucocyte-endothelium interactions between normal and adenocarcinoma bearing tissues in response to radiation.

    PubMed Central

    Wu, N. Z.; Ross, B. A.; Gulledge, C.; Klitzman, B.; Dodge, R.; Dewhirst, M. W.

    1994-01-01

    Previously, we demonstrated that the interaction between leucocytes and endothelial cells in tumour tissues is greatly diminished compared with normal tissues under several induced inflammatory conditions. Radiation has been reported to cause release of inflammatory mediators and to promote neutrophil adhesions to cultured endothelial monolayers. In this study, we tested the hypothesis that radiation would cause increased leucocyte rolling and adhesion in both tumour and normal tissues. We examined these two parameters in response to 6 Gy of gamma-radiation in mammary adenocarcinomas implanted into rat skinfold window chambers as well as normal (i.e. non-tumour-bearing) preparations. Leucocyte rolling and adhesion were measured in terms of flux of rolling leucocytes (F(rolling)) and density of adhering leucocytes (D(adhering)) in microvessels. F(rolling) and D(adhering) were measured in two groups of preparations: irradiated and control. In normal preparations, F(rolling) and D(adhering) were both increased significantly by radiation. In contrast, in adenocarcinoma-bearing preparations, F(rolling) and D(adhering) were either unchanged (in the tumour centre) or reduced (in tumour periphery and the normal tissue surrounding the tumour) by radiation. Radiation did not cause changes in haemodynamics in these preparations, thus the observed changes in leucocyte rolling and adhesion could not be accounted for by haemodynamic factors. These results indicate that: (1) in normal preparations, radiation could cause inflammation as manifested by increased leucocyte rolling and adhesion; and (2) in tumour-bearing preparations, radiation caused changes in the vascular surface properties such that they became less adhesive to leucocytes. Such differences in radiation response may have important implications for radiation therapy and provide new insights into the unique features of tumours. Images Figure 2 PMID:8180019

  13. Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth.

    PubMed

    Rao, C V; Desai, D; Kaul, B; Amin, S; Reddy, B S

    1992-11-16

    Propolis, a honey bee hive product, is thought to exhibit a broad spectrum of activities including antibiotic, antiviral, anti-inflammatory and tumor growth inhibition; some of the observed biological activities may be due to caffeic acid (cinnamic acid) esters that are present in propolis. In the present study we synthesized three caffeic acid esters, namely methyl caffeate (MC), phenylethyl caffeate (PEC) and phenylethyl dimethylcaffeate (PEDMC) and tested them against the 3,2'-dimethyl-4-aminobiphenyl, (DMAB, a colon and mammary carcinogen)-induced mutagenicity in Salmonella typhimurium strains TA 98 and TA 100. Also, the effect of these agents on the growth of human colon adenocarcinoma, HT-29 cells and activities of ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) was studied. Mutagenicity was induced in Salmonella typhimurium strains TA 98 and TA 100 plus S9 activation using 5 and 10 micrograms DMAB and antimutagenic activities of 0-150 microM MC, 0-60 microM PEC and 0-80 microM PEDMC were determined. The results indicate that MC, PEC and PEDMC were not mutagenic in the Salmonella tester system. DMAB-induced mutagenicity was significantly inhibited with 150 microM MC, 40-60 microM PEC and 40-80 microM PEDMC in both tester systems. Treatment of HT-29 colon adenocarcinoma cells with > 150 microM MC, 30 microM PEC and 20 microM PEDMC significantly inhibited the cell growth and syntheses of RNA, DNA and protein. ODC and PTK activities were also inhibited in HT-29 cells treated with different concentrations of MC, PEC and PEDMC. These results demonstrate that caffeic acid esters which are present in Propolis possess chemopreventive properties when tested in short-term assay systems.

  14. 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

  15. 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.

  16. 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...

  17. Protothecosis in a dog.

    PubMed

    Vince, Andrew R; Pinard, Chantale; Ogilvie, Adam T; Tan, Emmeline O; Abrams-Ogg, Anthony C G

    2014-10-01

    A case of a disseminated algal infection is reported in a young rough-coated collie dog with progressive neurologic deficits, blindness, and hemorrhagic diarrhea. Prototheca zopfii organisms were cultured from feces, urine, and blood. At necropsy, granulomas containing typical organisms were identified within the proximal colon, heart, kidneys, and eyes.

  18. 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.

  19. 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...

  20. Alcohol exposure in utero leads to enhanced prepubertal mammary development and alterations in mammary IGF and estradiol systems.

    PubMed

    Polanco, Tiffany A; Crismale-Gann, Catina; Cohick, Wendie S

    2011-08-01

    Exposure to alcohol during fetal development increases susceptibility to mammary cancer in adult rats. This study determined if early changes in mammary morphology and the insulin-like growth factor (IGF)/estradiol axis are involved in the mechanisms that underlie this increased susceptibility. Pregnant Sprague-Dawley rats were fed a liquid diet containing 6.7% ethanol (alcohol), an isocaloric liquid diet (pair-fed), or rat chow ad libitum from days 11 to 21 of gestation. At birth, female pups were cross-fostered to ad libitum-fed control dams. Offspring were euthanized at postnatal days (PND) 20, 40, or 80. Animals were injected with BrdU before euthanasia, then mammary glands, serum, and livers were collected. Mammary glands from animals exposed to alcohol in utero displayed increased epithelial cell proliferation and aromatase expression at PND 20 and 40. Mammary IGF-I mRNA was higher in alcohol-exposed animals relative to controls at PND 20, while mammary IGFBP-5 mRNA was lower in this group at PND 40. Hepatic IGF-I mRNA expression was increased at all time points in alcohol-exposed animals, however, circulating IGF-I levels were not altered. These data indicate that alcohol exposure in utero may advance mammary development via the IGF and estradiol systems, which could contribute to increased susceptibility to mammary cancer later in life.

  1. Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study.

    PubMed

    Stevens, Todd M; Kovalovsky, Andra O; Velosa, Claudia; Shi, Qiuying; Dai, Qian; Owen, Randall P; Bell, Walter C; Wei, Shi; Althof, Pamela A; Sanmann, Jennifer N; Sweeny, Larissa; Carroll, William R; Siegal, Gene P; Bullock, Martin J; Brandwein-Gensler, Margaret

    2015-08-01

    Mammary analog secretory carcinoma (MASC) is a recently recognized low-grade salivary carcinoma characterized by a specific ETV6 rearrangement. We describe 14 new MASCs and examine their immunophenotypic and genetic profiles in the context of look-alikes, namely, low-and high-grade salivary duct carcinoma and acinic cell carcinoma. ETV6 rearrangement, and robust expression of mammaglobin and S100, were demonstrated in 11/11, 14/14, and 12/14 MASCs, respectively. All low-grade salivary duct carcinomas coexpressed S100/mammaglobin (6/6); none harbored ETV6 rearrangements (0/5). Given that S100/mammaglobin coexpression and absence of zymogen granules are features of both MASC and low-grade salivary duct carcinoma, these two are best distinguished histologically. The former is predominantly an extraductal neoplasm with bubbly pink cytoplasm, whereas the latter is a distinct intraductal micropapillary and cribriform process. Querying ETV6 gene status may be necessary for difficult cases. No acinic cell carcinoma expressed mammaglobin (0/13) or harbored an ETV6 rearrangement (0/7); only 1/13 acinic cell carcinomas weakly expressed S100. DOG1 expression was limited or absent among all tumor types, except acinic cell carcinoma which expressed DOG1 diffusely in a canalicular pattern. Therefore, histology and immunohistochemistry (mammaglobin, S100, DOG1) suffices in distinguishing acinic cell carcinoma from both MASC and low-grade salivary duct carcinoma. HER2 (ERBB2) amplification was detected in only 1/10 acinic cell carcinomas, but none of the MASCs or low-grade salivary duct carcinomas tested. High-grade salivary duct carcinomas frequently expressed mammaglobin (11/18) and harbored HER2 amplifications (13/15); none harbored ETV6 rearrangements (0/12). High-grade salivary duct carcinomas can easily be distinguished from these other entities by histology and HER2 amplification.

  2. 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

  3. Ductal Adenocarcinoma of the Prostate: A Case Report

    PubMed Central

    Hayashi, Yutaro; Kawahara, Takashi; Iwashita, Hiromichi; Shimokihara, Kota; Tsutsumi, Sohgo; Takamoto, Daiji; Mochizuki, Taku; Hattori, Yusuke; Teranishi, Jun-ichi; Miyoshi, Yasuhide; Yumura, Yasushi; Yao, Masahiro; Inayama, Yoshiaki; Uemura, Hiroji

    2016-01-01

    Ductal adenocarcinoma is an unusual variant of adenocarcinoma of the prostate. A 73-year-old male was referred to our hospital for the further examination of an elevated prostate-specific antigen level of 23.4 ng/mL. Radical prostatectomy (RP) was performed based on the diagnosis obtained by a prostate needle biopsy. The RP specimen revealed ductal adenocarcinoma of the prostate with positive capsular penetration. We herein report a rare case of ductal adenocarcinoma of the prostate. PMID:28101029

  4. Immune cell location and function during post-natal mammary gland development.

    PubMed

    Reed, Johanna R; Schwertfeger, Kathryn L

    2010-09-01

    Post-natal mammary gland development requires complex interactions between the epithelial cells and various cell types within the stroma. Recent studies have illustrated the importance of immune cells and their mediators during the various stages of mammary gland development. However, the mechanisms by which these immune cells functionally contribute to mammary gland development are only beginning to be understood. This review provides an overview of the localization of immune cells within the mammary gland during the various stages of post-natal mammary gland development. Furthermore, recent studies are summarized that illustrate the mechanisms by which these cells are recruited to the mammary gland and their functional roles in mammary gland development.

  5. Mammary Cancer and Activation of Transposable Elements

    DTIC Science & Technology

    2013-09-01

    cytes and ADS-derived induced pluripotent stem cells (ADS-iPSCs) (19) and primary mouse ES cells to isolated sperm and oocytes (20). We selected an...051 59 5 92% H9-IMR90 5875 7 669 782 605 58 91% oocyte - ES cell (mouse) 4727 1 204 883 334 25 93% sperm - ES cell (mouse) 4580 4 364 748 1027 104 91...collaborator, Dr. Anne Peaston, developed a genetically engineered mouse model in which a specific mammary cell population is fluorescently marked upon

  6. Mouse Mammary Cancer Models - Mechanisms and Markers

    DTIC Science & Technology

    2001-08-01

    Wipl knockout mouse model and have shown defects in cell cycle control in cells derived from Wipl null animals. We are crossing these mice to mammary...compartment of the testes (13,14). Mice lacking Wipl are viable, but males show a reduced longevity and frequent runting (14). Wipl null males also show...predominates and thus the other TG/p53 mouse . Wnt-1 TG mice contain several copies nontumor components should not obscure any strong of a germline Wnt-1

  7. Characterization of Human Mammary Epithelial Stem Cells

    DTIC Science & Technology

    2008-10-01

    9 Appendix……………………………………………………………………………… 10 Eirew,P., Stingl,J., Raouf,A., Turashvili,G., Aparicio ,S., Emerman,J.T., and Eaves,C.J. A...Peter Eirew, John Stingl, Afshin Raouf, Gulisa Turashvili, Samuel Aparicio , Joanne Emerman and Connie Eaves. A method for quantifying normal human...Eirew, Afshin Raouf, John Stingl, Gulisa Turashvili, Allen Delaney, Joanne Emerman, Marco Marra and Samuel Aparicio . “Stem Cells in the Mammary Gland

  8. 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.

  9. Disruption of reelin signaling alters mammary gland morphogenesis

    PubMed Central

    Khialeeva, Elvira; Lane, Timothy F.; Carpenter, Ellen M.

    2011-01-01

    Reelin signaling is required for appropriate cell migration and ductal patterning during mammary gland morphogenesis. Dab1, an intracellular adaptor protein activated in response to reelin signaling, is expressed in the developing mammary bud and in luminal epithelial cells in the adult gland. Reelin protein is expressed in a complementary pattern, first in the epithelium overlying the mammary bud during embryogenesis and then in the myoepithelium and periductal stroma in the adult. Deletion in mouse of either reelin or Dab1 induced alterations in the development of the ductal network, including significant retardation in ductal elongation, decreased terminal branching, and thickening and disorganization of the luminal wall. At later stages, some mutant glands overcame these early delays, but went on to exhibit enlarged and chaotic ductal morphologies and decreased terminal branching: these phenotypes are suggestive of a role for reelin in spatial patterning or structural organization of the mammary epithelium. Isolated mammary epithelial cells exhibited decreased migration in response to exogenous reelin in vitro, a response that required Dab1. These observations highlight a role for reelin signaling in the directed migration of mammary epithelial cells driving ductal elongation into the mammary fat pad and provide the first evidence that reelin signaling may be crucial for regulating the migration and organization of non-neural tissues. PMID:21266412

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

    PubMed

    Haricharan, S; Li, Y

    2014-01-25

    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, programmed 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.

  11. A review of mammary ductoscopy in breast cancer.

    PubMed

    Yamamoto, Daigo; Tanaka, Kanji

    2004-01-01

    Breast carcinoma and hyperplasia are thought to start in the lining of the breast duct. Mammary ductoscopy is an emerging technique allowing direct visual access of the ductal system of the breast through the nipple. This article reviews and discusses the utility of mammary ductoscopy. Abnormalities can be identified successfully by mammary ductoscopy, and intraductal biopsy can be used when the tumor is a polypoid type. Ductal lavage using microcatheters is effective in identifying malignant cells in high-risk women and this has stimulated interest in exploring the role of mammary ductoscopy in breast cancer screening. Mammary ductoscopy combined with ductal lavage may have a role in the management of patients with nipple discharge, the guiding of breast-conserving surgery for cancer, and in screening for high-risk women. The addition of molecular and genetic analysis of cells obtained by mammary ductoscopy are likely to enhance the use of this technique. Mammary ductoscopy techniques are safe and appear useful for detecting abnormalities in the breast. The additional molecular biologic study or ductal lavage may enhance the ability to direct and limit subsequent surgery when removing the offending lesions.

  12. 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.

  13. CELL CONTACTS IN THE MOUSE MAMMARY GLAND

    PubMed Central

    Pitelka, Dorothy R.; Hamamoto, Susan T.; Duafala, Joan G.; Nemanic, Michael K.

    1973-01-01

    The nature and distribution of cell contacts have been examined in thin sections and freeze-fracture replicas of mammary gland samples from female C3H/Crgl mice at stages from birth through pregnancy, lactation, and postweaning involution. Epithelial cells of major mammary ducts at all stages examined are linked at their luminal borders by junctional complexes consisting of tight junctions, variable intermediate junctions, occasional small gap junctions, and one or more series of desmosomes. Scattered desmosomes and gap junctions link ductal epithelial and myoepithelial cells in all combinations; hemidesmosomes attach myoepithelial cells to the basal lamina. Freeze-fracture replicas confirm the erratic distribution of gap junctions and reveal a loose, irregular network of ridges comprising the continuous tight-junctional belts. Alveoli develop early in gestation and initially resemble ducts. Later, as alveoli and small ducts become actively secretory, they lose all desmosomes and most intermediate junctions, whereas tight and gap junctions persist, The tight-junctional network becomes compact and orderly, its undulating ridges oriented predominantly parallel to the luminal surface. It is suggested that these changes in junctional morphology, occurring in secretory cells around parturition, may be related to the greatly enhanced rate of movement of milk precursors and products through the lactating epithelium, or to the profound and recurrent changes in shape of secretory cells that occur in relation to myoepithelial cell contraction, or to both. PMID:4569313

  14. 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.

  15. Concentrations of cardiac Troponin I before and after ovariohysterectomy in 46 female dogs with pyometra

    PubMed Central

    Pelander, Lena; Hagman, Ragnvi; Häggström, Jens

    2008-01-01

    Background Canine pyometra is a common disease in countries where routine spaying of young dogs is not common practice. This disease is known to lead to systemic inflammation potentially affecting multiple organs in the body, including the heart. Cardiac-specific Troponin I (cTnI) is a sensitive marker of myocardial cell damage, which can result from ischemia, trauma, toxins or inflammation. Dogs with pyometra are also exposed to anaesthesia which can potentially result in myocardial cell damage. The aims of the study were 1) to evaluate the occurrence of myocardial cell damage as indicated by increased serum concentrations of cTnI in dogs with pyometra and relate these to presence of systemic inflammation and 2) to evaluate the change in cTnI-concentrations after anaesthesia and surgery. Methods Serum cTnI concentration was measured preoperatively and one day after surgery in 46 female dogs with pyometra and 15 female dogs that underwent surgery for other reasons (ovariohysterectomy and mammary tumours). Results Forty-six female dogs of different breeds diagnosed with pyometra were included. The dogs had a median age of 8.5 years (IQR 7.5–10) and a median weight of 29 kg (IQR 9–32). Of the 46 dogs, 37 (80%) fulfilled the chosen criteria for systemic inflammatory response syndrome (SIRS) at inclusion. Thirteen (28%) of the dogs had increased cTnI concentrations (> 0.2 μg/l) before surgery and 18 (39%) had increased cTnI-concentrations the day after surgery. The cTnI concentrations in the 13 dogs with increased preoperative cTnI concentrations decreased in 8 dogs, increased in 4 dogs, and was unchanged in one dog. Seven dogs with nondetectable preoperative cTnI concentrations had increased postoperative concentrations. The only significant association between the studied laboratory or clinical variables (including SIRS) and cTnI concentration was preoperative percentage band neutrophils (PBN) and postoperative cTnI concentration (P = 0.016). In total, 20 dogs

  16. Laparoscopic Diagnosis of Adenocarcinoma of the Appendix Mimicking Serous Papillary Adenocarcinoma of the Peritoneum

    PubMed Central

    Yoshimura, Mayumi; Terai, Yoshito; Konishi, Hiromi; Tanaka, Yoshimichi; Tanaka, Tomohito; Sasaki, Hiroshi; Ohmichi, Masahide

    2013-01-01

    Primary carcinoma of the vermiform appendix is a rare disease with few clinical symptoms. Accordingly, preoperative diagnosis of appendiceal cancer is challenging because of the lack of specific symptoms. We herein report a case of appendicular adenocarcinoma found unexpectedly during laparoscopic surgery in a 69-year-old Japanese female patient diagnosed with serous papillary adenocarcinoma, in order to determine whether optimal cytoreduction could successfully be achieved at the time of primary surgery. We performed diagnostic laparoscopic surgery in order to make a correct diagnosis based on the histological tissue. The vermiform appendix was found to contain a tumor measuring 1.5 cm wide and 4.5 cm long. Laparoscopic appendectomy, partial omentectomy, and partial resection of the lesion in the peritoneum were performed. The histological diagnosis was mucinous adenocarcinoma of the vermiform appendix, and the stage was T4NxM1. The patient received adjuvant chemotherapy with mFOLFOX 6 (5FU, leucovorin, and oxaliplatin). She achieved stable disease and was alive with disease eleven months after surgery. We therefore recommend that gynecologists should not rule out the possibility of appendiceal cancer, even in cases with preoperative findings similar to those of serous papillary adenocarcinoma of the peritoneum with peritoneal disseminated tumors. PMID:24383020

  17. Comparative value of clinical, cytological, and histopathological features in feline mammary gland tumors; an experimental model for the study of human breast cancer

    PubMed Central

    2013-01-01

    localized in the different regions, local invasiveness and enlarged nuclei were observed. The samples included 3 tumors of mammary glands mammary tumors were complex carcinomas (n = 2) and adenocarcinoma (n = 1). The histological grades of the 3 cases were as follows: grade II, (1/3); grade III, (2/3) with high mitotic index. The preferential localization of mammary neoplasms was in the inguinal lobe (1/3 case) and abdominal lobes (2/3 cases). Furthermore, 1case of the inguinal mass affected the left caudo-inguinal lobe and 2cases right cranio and caudo abdominal lobes. Conclusion The study concluded that cytology could be used as a quick, rapid, field diagnostic technique in combination with histopathology for the diagnosis of feline mammary tumors (FMTs). Our findings in feline MTs indicate that FMTs could be useful as an animal model of human breast cancer. Moreover, because of the similarity of the cytohistopathological findings in the human and feline mammary gland tumours, it is possible to use the same cytopathological criteria applied in human pathology for the diagnosis of feline mammary gland tumours. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2047361423103295 PMID:23941603

  18. Cutaneous toxoplasmosis in two dogs.

    PubMed

    Hoffmann, Aline Rodrigues; Cadieu, Jennifer; Kiupel, Matti; Lim, Ailam; Bolin, Steve R; Mansell, Joanne

    2012-05-01

    Cutaneous toxoplasmosis has been previously reported in human beings, rarely reported in cats, and reported in 1 dog with systemic toxoplasmosis. The present report describes 2 cases of cutaneous toxoplasmosis in 2 dogs treated with immunosuppressive therapy. One of the dogs developed generalized cutaneous pustules and pruritus, and the other dog only had a single subcutaneous nodule. Microscopically, skin biopsies showed moderate to severe pyogranulomatous and necrotizing dermatitis and panniculitis, with multifocal vasculitis and vascular thrombosis. Single or aggregates of protozoal tachyzoites were mostly intracytoplasmic and occasionally extracellular. The etiology was confirmed in both cases by immunohistochemistry and by polymerase chain reaction assays, which were followed by nucleic acid sequencing. Both patients were treated with clindamycin. The dog with generalized lesions developed pulmonary and neurological signs and was euthanized. The dog with a single nodule recovered completely with no remission of cutaneous lesions.

  19. Human-dog interactions in a guide-dog training program.

    PubMed

    Koda, N; Shimoju, S

    1999-06-01

    We analyzed dyadic interactions between 12 neutered dogs (6 females and 6 males) and 44 humans (20 women, 14 men, and 10 girls) who were unfamiliar with each other. We also examined the effect of sex differences in dogs and humans as well as age differences in humans on human-dog interactions in a guide-dog training program. Female dogs more actively regulated their distance from humans than male dogs. Dogs made contact with women more frequently than with men, and men made contact with dogs more frequently than women. Girls initiated interactions with dogs more frequently than women; girls formed reciprocal interactions with dogs less frequently than women.

  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. 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.

  2. Angiotensin converting enzyme from sheep mammary, lingual and other tissues.

    PubMed

    Rao, N Mallikarjuna; Udupa, E G Padmanabha

    2007-11-01

    Occurrence of angiotensin converting enzyme (ACE) in mammary gland and tongue taste epithelium was demonstrated for the first time. Six times higher ACE activity in lactating mammary gland, than non-lactating mammary gland, suggested pregnancy and lactation hormonal dependent expression of ACE in female mammals. ACE activity was highest in choroid plexus, less in spinal cord and moderate in cerebrum, medulla, cerebellum and pons. Distribution of ACE in different regions of skin, kidney and among other tissues was different. Presence of ACE in adrenal glands, pancreas, bone marrow and thyroid gland indicated functions other than blood pressure homeostasis for this enzyme.

  3. Extended immunologic and genetic lineage of mammary analogue secretory carcinoma of salivary glands.

    PubMed

    Ni, Hao; Zhang, Xue-Ping; Wang, Xiao-Tong; Xia, Qiu-Yuan; Lv, Jing-Huan; Wang, Xuan; Shi, Shan-Shan; Li, Rui; Zhou, Xiao-Jun; Rao, Qiu

    2016-12-01

    Mammary analogue secretory carcinoma (MASC) of salivary glands is a newly recognized tumor entity. To explore a more practical and convenient immunohistochemical approach to distinguish MASC from other tumors arising from salivary glands as well as to expand the immunologic and genetic lineage of MASC, we examined 17 MASCs using clinicopathologic, immunohistochemical, and molecular analyses. Eighteen cases of acinic cell carcinoma, 18 cases of adenoid cystic carcinoma, 22 cases of mucoepidermoid carcinoma, and 14 cases of basal cell adenocarcinoma were brought in for comparison. Seventeen MASCs shared similar architectures with not only intraluminal or intracellular secretion but also low-grade vesicular nuclei. In addition, they were all immunoreactive for S-100 and SOX-10, whereas only 3 of 17 demonstrated reactivity for GATA-3 and P63, and 4 of 17 were focally positive for CD117. ETV6 translocation was detected in 10 cases by fluorescence in situ hybridization, whereas intact ETV6 was noted in 2 cases. Our data proposed a combined immunohistochemical panel to distinguish MASC from other tumors arising from salivary glands and expanded the immunologic and genetic lineage of MASC.

  4. Carbogen-induced changes in rat mammary tumour oxygenation reported by near infrared spectroscopy

    PubMed Central

    Hull, E L; Conover, D L; Foster, T H

    1999-01-01

    We have evaluated the ability of steady-state, radially-resolved, broad-band near infrared diffuse reflectance spectroscopy to measure carbogen-induced changes in haemoglobin oxygen saturation (SO2) and total haemoglobin concentration in a rat R3230 mammary adenocarcinoma model in vivo. Detectable shifts toward higher saturations were evident in all tumours (n = 16) immediately after the onset of carbogen breathing. The SO2 reached a new equilibrium within 1 min and remained approximately constant during 200–300 s of administration. The return to baseline saturation was more gradual when carbogen delivery was stopped. The degree to which carbogen increased SO2 was variable among tumours, with a tendency for tumours with lower initial SO2 to exhibit larger changes. Tumour haemoglobin concentrations at the time of peak enhancement were also variable. In the majority of cases, haemoglobin concentration decreased in response to carbogen, indicating that increased tumour blood volume was not responsible for the observed elevation in SO2. We observed no apparent relationship between the extent of the change in tumour haemoglobin concentration and the magnitude of the change in the saturation. Near infrared diffuse reflectance spectroscopy provides a rapid, non-invasive means of monitoring spatially averaged changes in tumour haemoglobin oxygen saturation induced by oxygen modifiers. © 1999 Cancer Research Campaign PMID:10206281

  5. 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:…

  6. Eccrine adenocarcinoma of the footpads in 2 cats.

    PubMed Central

    Fuentealba, I C; Illanes, O G; Haines, D M

    2000-01-01

    Adenocarcinoma of sweat glands of the footpads was diagnosed in 2 cats. Clinical signs included lameness and swelling of multiple digits. Pulmonary metastasis was detected in one case. Diagnosis was based on histopathological and immunohistochemical findings. Eccrine adenocarcinoma should be included in the differential diagnosis of footpads lesions in aged cats. Images Figure 1. Figure 2. PMID:10816835

  7. Laparoscopic treatment of mucinous urachal adenocarcinoma with mucocele.

    PubMed

    Oberndoerfer, Marine; Bucher, Pascal; Caviezel, Alessandro; Platon, Alexandra; Ott, Vincent; Egger, Jean-François; Morel, Philippe

    2009-02-01

    We present a case of an asymptomatic 76-year-old woman treated laparoscopically for an urachal mucocele owing to a nonmetastatic urachal mucinous adenocarcinoma. Since laparoscopic en bloc resection of the urachus and partial cystectomy, the patient has been healthy and disease-free for 12 months. Modern surgical treatment of urachal adenocarcinoma is discussed in the light of this case.

  8. 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

  9. Is your dog empathic? Developing a Dog Emotional Reactivity Survey

    PubMed Central

    Szánthó, Flóra; Miklósi, Ádám; Kubinyi, Enikő

    2017-01-01

    Dogs' seemingly empathic behaviour attracts general and scientific attention alike. Behaviour tests are usually not sufficiently realistic to evoke empathic-like behaviour; therefore we decided to ask owners about their experiences with their dogs in emotionally loaded situations. Owners from Hungary (N = 591) and from Germany (N = 2283) were asked to rate their level of agreement on a 1–5 Likert scale with statements about the reactivity of their dogs to their emotions and to other dogs’ behaviour. We created two scales with satisfactory internal reliability: reactivity to the owner’s emotion and reactivity to other dogs’ behaviour. Based on an owner-dog personality matching theory, we hypothesised that the owner’s empathy, as measured by the subscale on the cooperativeness character factor of the human personality, will correlate with their dog’s emotional reactivity in emotionally loaded situations. In addition we also examined how anthropomorphism, contagious yawning, attitude toward the dog are related to emotional reactivity in dogs as perceived by the owner. In addition we examined how owners rate dog pictures. We found that the scale scores were largely independent from demographic and environmental variables like breed, sex, age, age at acquiring, keeping practices, training experiences and owner's age. However, anthropomorphic and emotional attitude of the owners probably biased the responses. In the German sample more empathic owners reported to have more emotionally reactive dog, as expected by the personality matching theory. More empathic owners reported to have fewer problems with their dogs and they rated a puppy picture as more cute in both countries. 62% of owners from Hungary and 36% of owner from Germany agreed with the statement “My dog is more important for me than any human being”. In Germany, more empathic owners agreed less with this statement and indicated that their dogs have a tendency for contagious yawning. Owners whose

  10. Chronic pancreatitis in dogs.

    PubMed

    Watson, Penny

    2012-08-01

    Chronic pancreatitis used to be considered uncommon in dogs, but recent pathological and clinical studies have confirmed that it is in fact a common and clinically significant disease. Clinical signs can vary from low-grade recurrent gastrointestinal signs to acute exacerbations that are indistinguishable from classical acute pancreatitis. Chronic pancreatitis is a significant cause of chronic pain in dogs, which must not be underestimated. It also results in progressive impairment of endocrine and exocrine function and the eventual development of diabetes mellitus or exocrine pancreatic insufficiency or both in some affected dogs at end stage. The etiology is unknown in most cases. Chronic pancreatitis shows an increased prevalence in certain breeds, and recent work in English Cocker Spaniels suggests it is part of a polysystemic immune-mediated disease in this breed. The histological and clinical appearance is different in different breeds, suggesting that etiologies may also be different. Diagnosis is challenging because the sensitivities of the available noninvasive tests are relatively low. However, with an increased index of suspicion, clinicians will recognize more cases that will allow them to institute supportive treatment to improve the quality of life of the patient.

  11. 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…

  12. 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

  13. 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

  14. Metastasis of Prostate Adenocarcinoma to the Testis

    PubMed Central

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana

    2016-01-01

    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  15. Effect of Age at Exposure on the Incidence of Lung and Mammary Cancer after Thoracic X-Ray Irradiation in Wistar Rats.

    PubMed

    Yamada, Yutaka; Iwata, Ken-Ichi; Blyth, Benjamin J; Doi, Kazutaka; Morioka, Takamitsu; Daino, Kazuhiro; Nishimura, Mayumi; Kakinuma, Shizuko; Shimada, Yoshiya

    2017-02-01

    Epidemiology studies have shown that children are at greater overall risk of radiation-induced cancer, but the modifying effect of age at exposure in different tissues is heterogeneous. Early epidemiology findings of increased lung cancer risk with increasing age at the time of exposure have been dismissed, with suggestions that the trend is an artefact from a failure to adequately correct for the effects of tobacco smoking. Yet, differing models used in subsequent analyses have shown that the increased susceptibility with age, counter to the overall solid tumor trend, can either be confirmed or discounted depending on the model parameters used. In this study, we analyzed the induction of tumors in female Wistar rats exposed to increasing thoracic doses of X-ray as neonates, juveniles or young adults, to allow the effect of age at exposure in this early period to be observed in the absence of any interactions with smoking. Histology was used to compare tumor subtypes among groups, and genomic DNA copy number alterations in a number of tumors arising after irradiation at different ages were examined. Induction of lung cancers increased with radiation dose, with the frequency of early occurring lung adenomas greater in rats irradiated at older ages. At the highest dose, the rats irradiated at 5 or 15 weeks of age showed increased age-specific rates of lung adenocarcinomas in later life compared to those irradiated at 1 week of age. However, thoracic mammary gland tumors induced by the highest dose at the later ages significantly decreased the lifespan in these groups, reducing the number of rats at risk of radiation-induced lung adenocarcinoma. There was no induction of mammary tumors outside of the irradiated field. Lung adenocarcinomas showed widespread DNA copy number aberrations at the chromosome level, but the only recurrent lesions were intragenic Fhit deletions and losses on chromosome 4. The results presented here suggest that the risk of radiation

  16. Notch in mammary gland development and breast cancer.

    PubMed

    Politi, Katerina; Feirt, Nikki; Kitajewski, Jan

    2004-10-01

    Notch signaling has been implicated in many processes including cell fate determination and oncogenesis. In mice, the Notch1 and Notch4 genes are both targets for insertion and rearrangement by the mouse mammary tumor virus and these mutations promote epithelial mammary tumorigenesis. Moreover, expression of a constitutively active form of Notch4 in mammary epithelial cells inhibits epithelial differentiation and leads to tumor formation in this organ. These data implicate the Notch pathway in breast tumorigenesis and provide the foundation for future experiments that will aid in our understanding of the role of Notch in human breast cancer development. Here, we review studies of mammary tumorigenesis induced by Notch in mouse and in vitro culture models providing evidence that Notch activation is a causal factor in human breast cancer.

  17. 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. ...

  18. Vaginal myofibroblastoma with glands expressing mammary and prostatic antigens.

    PubMed

    Wallenfels, I; Chlumská, A

    2012-01-01

    A case of unusual vaginal myofibroblastoma containing glands which expressed mammary and prostatic markers is described. The tumor occurred in 70-year-old woman in the proximal third of the vagina. It showed morphology and immunophenotype typical of so-called cervicovaginal myofibroblastoma. The peripheral zone of the lesion contained a few groups of glands suggesting vaginal adenosis or prostatic-type glands on initial examination. The glands showed a surprising simultaneous expression of mammary markers mammaglobin and GCDFP-15 and prostatic markers prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP). Immunostains for alpha-smooth muscle actin, p63 and CD10 highlighted the myoepithelial cell layer of the glands. The finding indicates that simultaneous use of both mammary and prostatic markers for examination of unusual glandular lesions in the vulvovaginal location can be helpful for an exact diagnosis, and can contribute to better understanding of prostatic and mammary differentiations in the female lower genital tract.

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

    PubMed Central

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

    2016-01-01

    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

  20. Genes affected by mouse mammary tumor virus (MMTV) proviral insertions in mouse mammary tumors are deregulated or mutated in primary human mammary tumors

    PubMed Central

    Callahan, Robert; Mudunuri, Uma; Bargo, Sharon; Raafat, Ahmed; McCurdy, David; Boulanger, Corinne; Lowther, William; Stephens, Robert; Luke, Brian T.; Stewart, Claudia; Wu, Xiaolin; Munroe, David; Smith, Gilbert H.

    2012-01-01

    The accumulation of mutations is a contributing factor in the initiation of premalignant mammary lesions and their progression to malignancy and metastasis. We have used a mouse model in which the carcinogen is the mouse mammary tumor virus (MMTV) which induces clonal premalignant mammary lesions and malignant mammary tumors by insertional mutagenesis. Identification of the genes and signaling pathways affected in MMTV-induced mouse mammary lesions provides a rationale for determining whether genetic alteration of the human orthologues of these genes/pathways may contribute to human breast carcinogenesis. A high-throughput platform for inverse PCR to identify MMTV-host junction fragments and their nucleotide sequences in a large panel of MMTV-induced lesions was developed. Validation of the genes affected by MMTV-insertion was carried out by microarray analysis. Common integration site (CIS) means that the gene was altered by an MMTV proviral insertion in at least two independent lesions arising in different hosts. Three of the new genes identified as CIS for MMTV were assayed for their capability to confer on HC11 mouse mammary epithelial cells the ability for invasion, anchorage independent growth and tumor development in nude mice. Analysis of MMTV induced mammary premalignant hyperplastic outgrowth (HOG) lines and mammary tumors led to the identification of CIS restricted to 35 loci. Within these loci members of the Wnt, Fgf and Rspo gene families plus two linked genes (Npm3 and Ddn) were frequently activated in tumors induced by MMTV. A second group of 15 CIS occur at a low frequency (2-5 observations) in mammary HOGs or tumors. In this latter group the expression of either Phf19 or Sdc2 was shown to increase HC11 cells invasion capability. Foxl1 expression conferred on HC11 cells the capability for anchorage-independent colony formation in soft agar and tumor development in nude mice. The published transcriptome and nucleotide sequence analysis of gene

  1. 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

  2. [Estrogen receptors and the mammary gland].

    PubMed

    Barrón, A; Bermejo, L; Castro, I

    1997-01-01

    For several decades it has been known that steroid hormones, estrogen and progesterone, regulate some genes involved in the growth, proliferation and differentiation of the mammary-gland in animals and humans. In the last years, the presence or absence of the nuclear estrogen receptor has been used by clinicians as a marker for tumor malignancy, as a prognostic index or as an important parameter for hormonal therapy with anti-estrogenic compounds of some hormone-dependent breast cancers. This review shows some advances in the knowledge of the structure, function, molecular mechanisms of estrogenic activity, and interaction with proteins like protooncogenes and growth factors. Also, we refer to the role of the estrogen receptor in the physiophatology of breast cancer.

  3. Milk protein concentrations in galactorrhoeic mammary secretions.

    PubMed

    Yap, P L; Pryde, E A; McClelland, D B

    1980-02-01

    Milk protein concentrations were determined either by double antibody radioimmunoassay (IgA) or single radial immunodiffusion (IgG, lactoferrin, lysozyme and albumin) in the mammayr secretions of one nulliparous and three parous female patients with galactorrhoea due to hyperprolactinaemia. Concentrations of all the proteins studied were found to be similar to the concentrations observed in post-partum colostrum. In particular, secretory IgA was the only form of IgA detected in galactorrhoeic secretions. It is suggested that hyperprolactinaemia alone can result in increased mammary synthesis of the milk proteins since the steroid changes associated with a full-term pregnancy and delivery of the placenta did not immediately precede the galactorrhoea in three of the four patients studied.

  4. Effect of Reproductive History on Mammary Epithelial Biology

    DTIC Science & Technology

    2001-05-01

    Reproductive History on Mammary Epithelial Biology PRINCIPAL INVESTIGATOR: Lewis A. Chodosh, M.D., Ph.D. CONTRACTING ORGANIZATION : University of Pennsylvania...9348 Organization : University of Pennsylvania Those portions of the technical data contained in this report marked as limited rights data shall not...History on Mammary Epithelial DAMD17-99-1-9348 Biology 6. AUTHOR(S) Lewis A. Chodosh, M.D., Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8

  5. 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

  6. Role of p53 Mammary Epithelial Cell Senescence

    DTIC Science & Technology

    2005-05-01

    susceptibility to oncogenesis exist in the normal mammary tissue, the milk -forming ducts of the mammary gland (for review [2]). Coupled with information...HMECs [25]. proportion of preselection HMECs [8]. The senescence associated with the ’selection’ phase in Human milk is an easily available source of...which has precluded their detailed biochemical proliferation at this stage is dependent on the pRb/p16 study [2,18]. Most of the work on milk cells has

  7. Hippo pathway in mammary gland development and breast cancer.

    PubMed

    Shi, Peiguo; Feng, Jing; Chen, Ceshi

    2015-01-01

    Accumulated evidence suggests that the Hippo signaling pathway plays crucial roles in mammary gland development and breast cancer. Key components of the Hippo pathway regulate breast epithelial cell proliferation, migration, invasion, and stemness. Additionally, the Hippo pathway regulates breast tumor growth, metastasis, and drug resistance. It is expected that the Hippo pathway will provide novel therapeutic targets for breast cancer. This review will discuss and summarize the roles of several core components of the Hippo pathway in mammary gland development and breast cancer.

  8. Mechanism of Environmental Carcinogen-Induced Mammary Tumorigenesis

    DTIC Science & Technology

    2001-10-01

    Detrick, Maryland 21702-5012. 13. ABSTRACT (Maximum 200 Words) Environmental pollutants such as polycyclic aromatic hydrocarbons ( PAH ) are believed to...of treatment of 7,12-dimethylbenz(a)anthracene (DMBA), a member of the PAH family. Estrogen is indispensable for the DMBA-mediated mammary...tumorigenesis. We hypothesize that DMBA-mediated rat mammary tumorigenesis involves in the activation of protooncogene Mdm2 which in turn negatively regulates

  9. 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.

  10. 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

  11. Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis

    PubMed Central

    Ali, Moustafa R K; Ibrahim, Ibrahim M; Ali, Hala R; Selim, Salah A; El-Sayed, Mostafa A

    2016-01-01

    Plasmonic photothermal therapy (PPTT) is a cancer therapy in which gold nanorods are injected at the site of a tumor before near-infrared light is transiently applied to the tumor causing localized cell death. Previously, PPTT studies have been carried out on xenograft mice models. Herein, we report a study showing the feasibility of PPTT as applied to natural tumors in the mammary glands of dogs and cats, which more realistically represent their human equivalents at the molecular level. We optimized a regime of three low PPTT doses at 2-week intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland tumors from seven animals. Histopathology, X-ray, blood profiles, and comprehensive examinations were used for both the diagnosis and the evaluation of tumor statuses before and after treatment. Histopathology results showed an obvious reduction in the cancer grade shortly after the first treatment and a complete regression after the third treatment. Blood tests showed no obvious change in liver and kidney functions. Similarly, X-ray diffraction showed no metastasis after 1 year of treatment. In conclusion, our study suggests the feasibility of applying the gold nanorods-PPTT on natural tumors in dogs and cats without any relapse or toxicity effects after 1 year of treatment. PMID:27703351

  12. 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

  13. Dog Mathematics: Exploring Base-4

    ERIC Educational Resources Information Center

    Kurz, Terri L.; Yanik, H. Bahadir; Lee, Mi Yeon

    2016-01-01

    Using a dog's paw as a basis for numerical representation, sixth grade students explored how to count and regroup using the dog's four digital pads. Teachers can connect these base-4 explorations to the conceptual meaning of place value and regrouping using base-10.

  14. 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.

  15. Pancreatic torsion in a dog

    PubMed Central

    Brabson, Tamera L.; Maki, Lynn C.; Newell, Susan M.; Ralphs, S. Christopher

    2015-01-01

    A 6-month-old male intact Cane Corso mastiff dog was presented for a recent history of vomiting, abdominal pain, and lethargy. A diagnosis of pancreatic torsion was made during abdominal exploratory surgery and was confirmed with histopathology. The dog underwent partial pancreatectomy and recovered with no complications. PMID:25969579

  16. Epidemiology and Molecular Typing of Trypanosoma cruzi in Naturally-Infected Hound Dogs and Associated Triatomine Vectors in Texas, USA

    PubMed Central

    Curtis-Robles, Rachel; Snowden, Karen F.; Dominguez, Brandon; Dinges, Lewis; Rodgers, Sandy; Mays, Glennon

    2017-01-01

    Background Trypanosoma cruzi is the etiologic agent of Chagas disease throughout the Americas. Few population-level studies have examined the epidemiology of canine infection and strain types of T. cruzi that infect canines in the USA. We conducted a cross-sectional study of T. cruzi infection in working hound dogs in south central Texas, including analysis of triatomine vectors collected within kennel environments. Methodology/Principle Findings Paired IFA and Chagas Stat-Pak serological testing showed an overall seroprevalence of 57.6% (n = 85), with significant variation across kennels. Dog age had a marginally significant effect on seropositivity, with one year of age increase associated with a 19.6% increase in odds of being seropositive (odds ratio 95% CI 0.996–1.435; p = 0.055). PCR analyses of blood revealed 17.4% of dogs harbored parasite DNA in their blood, including both seronegative and seropositive dogs. Molecular screening of organs from opportunistically sampled seropositive dogs revealed parasite DNA in heart, uterus, and mammary tissues. Strain-typing showed parasite discrete typing units (DTU) TcI and TcIV present in dog samples, including a co-occurrence of both DTUs in two individual dogs. Bloodmeal analysis of Triatoma gerstaeckeri and Triatoma sanguisuga insects collected from the kennels revealed exclusively dog DNA. Vector infection with T. cruzi was 80.6% (n = 36), in which T. gerstaeckeri disproportionately harbored TcI (p = 0.045) and T. sanguisuga disproportionately harbored TcIV (p = 0.029). Tracing infection status across dog litters showed some seropositive offspring of seronegative dams, suggesting infection of pups from local triatomine vectors rather than congenital transmission. Conclusions/Significance Canine kennels are high-risk environments for T. cruzi transmission, in which dogs likely serve as the predominant parasite reservoir. Disease and death of working dogs from Chagas disease is associated with unmeasured yet

  17. Soy isoflavones increase latency of spontaneous mammary tumors in mice.

    PubMed

    Jin, Zeming; MacDonald, Ruth S

    2002-10-01

    Soy protein, with and without isoflavones, is being added to foods by manufacturers in response to the Food and Drug Administration (FDA)-approved health claim for cardiovascular protection. Furthermore, soy isoflavones are increasingly consumed by women in the United States as an alternative to hormone replacement therapy. The role of these phytoestrogens in breast cancer is controversial. Although exposure of rodents to soy isoflavones during the perinatal period appears to reduce mammary cancer formation, exposure in utero or during adulthood may increase tumor growth. The mouse mammary tumor virus (MMTV)-neu mouse spontaneously develops mammary tumors due to overexpression of the ErbB-2/neu/HER2 oncogene. This model is comparable with human breast cancer because overexpression of the neu oncogene occurs in 20-40% of human breast cancers. We fed MMTV-neu mice AIN-93G diets containing no isoflavones, 250 mg/kg genistein, 250 mg/kg daidzein or an isoflavone mixture (NovaSoy, equivalent to 250 mg genistein/kg) from 7 wk of age. Mammary tumor latency was significantly delayed in mice fed isoflavones compared with the control. Once tumors formed, however, the isoflavones did not reduce the number or size of tumors such that at 34 wk of age there were no differences in tumor burden among the treatment groups. Hence, in the MMTV-neu mouse, soy isoflavones delayed mammary tumorigenesis. Further studies are warranted to define the cellular mechanisms through which these compounds affect mammary tumorigenesis in this model.

  18. Mammary hypoplasia: not every breast can produce sufficient milk.

    PubMed

    Arbour, Megan W; Kessler, Julia Lange

    2013-01-01

    Breast milk is considered the optimal form of nutrition for newborn infants. Current recommendations are to breastfeed for 6 months. Not all women are able to breastfeed. Mammary hypoplasia is a primary cause of failed lactogenesis II, whereby the mother is unable to produce an adequate milk volume. Women with mammary hypoplasia often have normal hormone levels and innervation but lack sufficient glandular tissue to produce an adequate milk supply to sustain their infant. The etiology of this rare condition is unclear, although there are theories that refer to genetic predisposition and estrogenic environmental exposures in select agricultural environments. Women with mammary hypoplasia may not exhibit the typical breast changes associated with pregnancy and may fail to lactate postpartum. Breasts of women with mammary hypoplasia may be widely spaced (1.5 inches or greater), asymmetric, or tuberous in nature. Awareness of the history and clinical signs of mammary hypoplasia during the prenatal period and immediate postpartum increases the likelihood that women will receive the needed education and physical and emotional support and encouragement. Several medications and herbs demonstrate some efficacy in increasing breast milk production in women with mammary hypoplasia.

  19. The role of tight junctions in mammary gland function.

    PubMed

    Stelwagen, Kerst; Singh, Kuljeet

    2014-03-01

    Tight junctions (TJ) are cellular structures that facilitate cell-cell communication and are important in maintaining the three-dimensional structure of epithelia. It is only during the last two decades that the molecular make-up of TJ is becoming unravelled, with two major transmembrane-spanning structural protein families, called occludin and claudins, being the true constituents of the TJ. These TJ proteins are linked via specific scaffolding proteins to the cell's cytoskeleton. In the mammary gland TJ between adjacent secretory epithelial cells are formed during lactogenesis and are instrumental in establishing and maintaining milk synthesis and secretion, whereas TJ integrity is compromised during mammary involution and also as result of mastitis and periods of mammary inflamation (including mastitis). They prevent the paracellular transport of ions and small molecules between the blood and milk compartments. Formation of intact TJ at the start of lactation is important for the establishment of the lactation. Conversely, loss of TJ integrity has been linked to reduced milk secretion and mammary function and increased paracellular transport of blood components into the milk and vice versa. In addition to acting as a paracellular barrier, the TJ is increasingly linked to playing an active role in intracellular signalling. This review focusses on the role of TJ in mammary function of the normal, non-malignant mammary gland, predominantly in ruminants, the major dairy producing species.

  20. 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.

  1. 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

  2. A service dog in group.

    PubMed

    Rothberg, Brian; Collins, Emily

    2015-04-01

    Service dogs are sanctioned by the Americans with Disabilities Act as having protected rights allowing them to assist owners with disabilities. These dogs are appearing with increasing frequency in healthcare settings, and it is important for healthcare providers to understand the rules and regulations given to service animals and owners. We discuss processes that transpired when a service dog was brought into a psychodynamic psychotherapy group. The purpose of this paper is to highlight the unintended consequences of the Americans with Disabilities Act of 2010 as it concerns service dogs and the impact on the group process. Problems resulting from the introduction of service dogs into therapy groups should be anticipated and explicitly discussed in the course of the group's transactions.

  3. Do Dog Behavioral Characteristics Predict the Quality of the Relationship between Dogs and Their Owners?

    PubMed

    Hoffman, Christy L; Chen, Pan; Serpell, James A; Jacobson, Kristen C

    This paper explores whether dog behavioral characteristics predict the quality of the relationship between dogs and their owners (i.e., owner attachment to dog), and whether relations between dog behavior and owner attachment are moderated by demographic characteristics. In this study, N = 92 children and N = 60 adults from 60 dog-owning families completed questionnaires about their attachment to their pet dog, their level of responsibility for that dog, and their general attitudes toward pets. They also rated their dogs on observable behavioral characteristics. Individuals who held positive attitudes about pets and who provided much of their dog's care reported stronger attachments to their dogs. The strength of owners' attachments to their dogs was associated with dog trainability and separation problems. Relationships between owner attachment and both dog excitability and attention-seeking behavior were further moderated by demographic characteristics: for Caucasians but not for non-Caucasians, dog excitability was negatively associated with owner attachment to dog; and for adults, dog attention-seeking behavior was positively associated with owner attachment, but children tended to be highly attached to their dogs, regardless of their dogs' attention-seeking behaviors. This study demonstrates that certain dog behavioral traits are indeed associated with the strength of owners' attachments to their dogs.

  4. Thyroid cancer in dogs: an update based on 638 cases (1995-2005).

    PubMed

    Wucherer, Katja L; Wilke, Vicki

    2010-01-01

    The goal of this study was to update the descriptive statistics of thyroid cancer by using data from multiple institutions collected through the Veterinary Medical Database (VMDB). Information was collected and reported from cases of canine thyroid cancer submitted to the VMDB between January 1, 1995 and December 31, 2005. Odds ratio (OR) analysis was performed on breeds that had > or =3% of the total number of dogs with thyroid cancer; ORs for each age category were also determined. Thyroid cancer represented 1.1% of all neoplasms during the time period of interest. Golden retrievers, beagles, and Siberian huskies all had significantly increased ORs for developing thyroid cancer. No sex predisposition was evident, but dogs between 10 and 15 years of age had a significantly increased chance of developing thyroid disease. Carcinomas and adenocarcinomas represented 90% of thyroid cancers, while adenomas represented 9.3%. Thyroid carcinoma and adenocarcinoma continue to be uncommon in our canine population. Older dogs are still more commonly affected, and this study is in agreement with previous studies that golden retrievers and beagles are overrepresented. A new finding is that Siberian huskies are also overrepresented. Carcinomas represent a much higher proportion of thyroid cancers than previously reported, and adenomas are likely incidental findings on necropsy. Thyroid cancer should be high on the list of differentials for a neck mass in older, large-breed dogs, as they make up 1.1% of the cancer cases reported. The overwhelming majority of thyroid cancers are carcinomas, and they are most common in golden retrievers, beagles, and Siberian huskies.

  5. 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.

  6. 38 CFR 17.148 - Service dogs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Service dogs. 17.148..., Sensory, and Rehabilitative Aids § 17.148 Service dogs. (a) Definitions. For the purposes of this section: Service dogs are guide or service dogs prescribed for a disabled veteran under this section. (b)...

  7. Hypoadrenocorticism in a kindred of Pomeranian dogs.

    PubMed

    Mooney, Erin T; Hammond, Tara N; Mahony, Orla M

    2015-01-01

    Three adult Pomeranian dogs, full siblings from 2 litters, were diagnosed with primary hypoadrenocorticism following onset of hypoadrenal crisis. Review of the family history revealed the dogs' maternal grandmother also had hypoadrenocorticism. All 4 dogs were pedigree-certified by the American Kennel Club. An inherited basis for hypoadrenocorticism is proposed in these Pomeranian dogs.

  8. Clinicopathologic features and prognosis of duodenal adenocarcinoma and comparison with ampullary and pancreatic ductal adenocarcinoma.

    PubMed

    Zenali, Maryam; Overman, Michael J; Rashid, Asif; Broaddus, Russell B; Wang, Hua; Katz, Matthew H; Fleming, Jason B; Abbruzzese, James L; Wang, Huamin

    2013-12-01

    Because of the rarity of duodenal adenocarcinoma (DAC), the clinicopathologic features and prognostication data for DAC are limited. There are no published studies directly comparing the prognosis of DAC to that of ampullary adenocarcinoma (AA) and of pancreatic ductal adenocarcinoma (PDA) after resection. In this study, we examined the clinicopathologic features of 68 patients with DAC, 92 patients with AA, and 126 patients with PDA who underwent resection. Patient clinicopathologic and survival information were extracted from medical records. Statistical analysis was performed using Statistical Package for the Social Sciences with 2-sided significance level of .05. Patients with DAC had higher American Joint Committee on Cancer (AJCC) stage than AA patients (P = .001). Lymph node metastasis (P = .013) and AJCC stage (P = .02) correlated with overall survival in DAC patients. Patients with DAC or AA had lower frequencies of lymph node metastasis and positive margin and better survival than those with PDA (P < .05). However, no differences in nodal metastasis, margin status, or survival were observed between DAC patients and those with AA. Our study showed that lymph node metastasis and AJCC stage are important prognostic factors for overall survival in DAC patients. Patients with DAC had less frequent nodal metastasis and better prognosis than those with PDA. There was no significant difference in prognosis between DAC and AA.

  9. Abiraterone Acetate and Castration Resistant Ductal Adenocarcinoma of the Prostate

    PubMed Central

    Linden-Castro, Edgar; Pelayo-Nieto, Marcela; Alias-Melgar, Alejandro; Espinosa-Perezgrovas, Daniel; Ramirez-Galindo, Ivan; Catalan-Quinto, Gabriel

    2014-01-01

    Ductal adenocarcinoma of the prostate is a rare histological variant that only represents <1% of prostate tumors. This histological variant has several important clinical implications with respect to their evolution, clinical prognosis, and treatment. We report the case of a 64-year-old patient with ductal adenocarcinoma of the prostate, which progresses to castration-resistant prostate cancer, that was treated with abiraterone acetate with good clinical response, to our knowledge, the first case of ductal adenocarcinoma of the prostate in treatment with abiraterone acetate. PMID:24891969

  10. 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. PMID:27622191

  11. [Secondary neoplasms of the larynx from a colonic adenocarcinoma].

    PubMed

    Dadkhah, Naser; Hahn, Christoffer

    2015-01-26

    Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, followed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx are extremely rare. Tumours spreading to the larynx may be asymptomatic or may result in hoarseness, stridor or airway obstruction. Patients with metastasis of colonic adenocarcinoma to the larynx usually present with disseminated disease. We present a case of an isolated laryngeal metastasis from a colonic adenocarcinoma. The patient was treated with endoscopic surgery and radiation.

  12. Duodenal adenocarcinoma presenting as a mass with aneurismal dilatation.

    PubMed

    Mama, Nadia; Ben Slama, Aïda; Arifa, Nadia; Kadri, Khaled; Sriha, Badreddine; Ksiaa, Mehdi; Jemni, Hela; Tlili-Graiess, Kalthoum

    2014-01-01

    Duodenal adenocarcinoma is frequent. Aneurysmal dilatation of the small bowel is reported to be a lymphoma characteristic imaging finding. A 57-year-old male was found to have a duodenal adenocarcinoma with aneurismal dilatation on imaging which is an exceptional feature. On laparotomy, the wall thickening of the dilated duodenum extended to the first jejunal loop, with multiple mesenteric lymph nodes and ascites. Segmental palliative resection with gastro-entero-anastomosis was done. Histopathology revealed a moderately differentiated adenocarcinoma with neuro-endocrine differentiation foci. Wide areas of necrosis and vascular emboli were responsible for the radiological feature of the dilated duodenum with wall thickening.

  13. Biomarkers in pancreatic adenocarcinoma: current perspectives

    PubMed Central

    Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. PMID:28003762

  14. Preclinical models of pancreatic ductal adenocarcinoma.

    PubMed

    Hwang, Chang-Il; Boj, Sylvia F; Clevers, Hans; Tuveson, David A

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDA) is one of the most difficult human malignancies to treat. The 5-year survival rate of PDA patients is 7% and PDA is predicted to become the second leading cancer-related cause of death in the USA. Despite intensive efforts, the translation of findings in preclinical studies has been ineffective, due partially to the lack of preclinical models that faithfully recapitulate features of human PDA. Here, we review current preclinical models for human PDA (eg human PDA cell lines, cell line-based xenografts and patient-derived tumour xenografts). In addition, we discuss potential applications of the recently developed pancreatic ductal organoids, three-dimensional culture systems and organoid-based xenografts as new preclinical models for PDA.

  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. Mammary sensitivity to protein restriction and re-alimentation.

    PubMed

    Goodwill, M G; Jessop, N S; Oldham, J D

    1996-09-01

    The present study tested the influence of protein undernutrition and re-alimentation on mammary gland size and secretory cell activity in lactating rats. During gestation, female Sprague-Dawley rats were offered a high-protein diet (215 g crude protein (N x 6.25; CP)/kg DM; H); litters were standardized to twelve pups at parturition. During lactation, two diets were offered ad libitum, diet H and a low-protein diet (90 g CP/kg DM; L). Lactational dietary treatments were the supply ad libitum of either diet H (HHH) or diet L (LLL) for the first 12 d of lactation, or diet L transferring to diet H on either day 6 (LHH) or 9 (LLH) of lactation. On days 1, 6, 9 and 12 of lactation, rats from each group (n > or = 6) were used to estimate mammary dry mass, fat, protein, DNA and RNA; the activities of lactose synthetase (EC 2.4.1.22) enzyme and Na+,K(+)-ATPase (EC 3.6.1.37) were also measured. Rats offered a diet considered protein sufficient (H) from day 1 of lactation showed a decrease in mammary dry mass and fat but an increase in DNA, RNA and protein on day 6, after which there was no further change, except for mammary protein which continued to increase. However, rats offered diet L showed a steady loss in mammary mass and fat throughout the 12 d lactation period and no change in mammary DNA, RNA or protein. Rats previously protein restricted for either the first 6 or 9 d of lactation had their mammary dry mass and mammary fat loss halted and showed a rapid increase in mammary DNA, RNA and protein on re-alimentation. Lactose production in group HHH, as measured by lactose synthetase activity, was similar on days 1 and 6 of lactation, after which a significant increase was seen. Protein-restricted rats showed no change in lactose synthetase activity during the 12 d experimental period. Changing from diet L to diet H led to a significant increase in lactose synthetase activity to levels comparable with those offered diet H from day 1. These results show that rats

  17. Relationship Between Scarring and Dog Aggression in Pit Bull-Type Dogs Involved in Organized Dogfighting.

    PubMed

    Miller, Katherine A; Touroo, Rachel; Spain, C Victor; Jones, Kelly; Reid, Pamela; Lockwood, Randall

    2016-11-15

    When pit bull-type dogs are seized in an investigation of organized dogfighting, heavily scarred dogs are often assumed to be highly dog aggressive due to a history of fighting. These dogs may be deemed dangerous and euthanized based on scarring alone. We analyzed our existing data on dogs seized from four dogfighting investigations, examining the relationship between the dogs' scars with aggression towards other dogs. Scar and wound data were tallied in three body zones where dogfighting injuries tend to be concentrated. Dog aggression was assessed using a model dog and a friendly stimulus dog in a standardized behavior evaluation. Scarring and dog aggression were significantly related, more strongly among male (Fisher's Exact p < 0.001) than female dogs (Fisher's Exact p = 0.05). Ten or more scars in the three body zones was a reasonable threshold with which to classify a dog as high risk for dog aggression: 82% of males and 60% of females with such scarring displayed dog aggression. However, because many unscarred dogs were dog aggressive while some highly scarred dogs were not, we recommend collecting behavioral information to supplement scar counts when making disposition decisions about dogs seized in dogfighting investigations.

  18. Complex population structure in African village dogs and its implications for inferring dog domestication history.

    PubMed

    Boyko, Adam R; Boyko, Ryan H; Boyko, Corin M; Parker, Heidi G; Castelhano, Marta; Corey, Liz; Degenhardt, Jeremiah D; Auton, Adam; Hedimbi, Marius; Kityo, Robert; Ostrander, Elaine A; Schoenebeck, Jeffrey; Todhunter, Rory J; Jones, Paul; Bustamante, Carlos D

    2009-08-18

    High genetic diversity of East Asian village dogs has recently been used to argue for an East Asian origin of the domestic dog. However, global village dog genetic diversity and the extent to which semiferal village dogs represent distinct, indigenous populations instead of admixtures of various dog breeds has not been quantified. Understanding these issues is critical to properly reconstructing the timing, number, and locations of dog domestication. To address these questions, we sampled 318 village dogs from 7 regions in Egypt, Uganda, and Namibia, measuring genetic diversity >680 bp of the mitochondrial D-loop, 300 SNPs, and 89 microsatellite markers. We also analyzed breed dogs, including putatively African breeds (Afghan hounds, Basenjis, Pharaoh hounds, Rhodesian ridgebacks, and Salukis), Puerto Rican street dogs, and mixed breed dogs from the United States. Village dogs from most African regions appear genetically distinct from non-native breed and mixed-breed dogs, although some individuals cluster genetically with Puerto Rican dogs or United States breed mixes instead of with neighboring village dogs. Thus, African village dogs are a mosaic of indigenous dogs descended from early migrants to Africa, and non-native, breed-admixed individuals. Among putatively African breeds, Pharaoh hounds, and Rhodesian ridgebacks clustered with non-native rather than indigenous African dogs, suggesting they have predominantly non-African origins. Surprisingly, we find similar mtDNA haplotype diversity in African and East Asian village dogs, potentially calling into question the hypothesis of an East Asian origin for dog domestication.

  19. Complex population structure in African village dogs and its implications for inferring dog domestication history

    PubMed Central

    Boyko, Adam R.; Boyko, Ryan H.; Boyko, Corin M.; Parker, Heidi G.; Castelhano, Marta; Corey, Liz; Degenhardt, Jeremiah D.; Auton, Adam; Hedimbi, Marius; Kityo, Robert; Ostrander, Elaine A.; Schoenebeck, Jeffrey; Todhunter, Rory J.; Jones, Paul; Bustamante, Carlos D.

    2009-01-01

    High genetic diversity of East Asian village dogs has recently been used to argue for an East Asian origin of the domestic dog. However, global village dog genetic diversity and the extent to which semiferal village dogs represent distinct, indigenous populations instead of admixtures of various dog breeds has not been quantified. Understanding these issues is critical to properly reconstructing the timing, number, and locations of dog domestication. To address these questions, we sampled 318 village dogs from 7 regions in Egypt, Uganda, and Namibia, measuring genetic diversity >680 bp of the mitochondrial D-loop, 300 SNPs, and 89 microsatellite markers. We also analyzed breed dogs, including putatively African breeds (Afghan hounds, Basenjis, Pharaoh hounds, Rhodesian ridgebacks, and Salukis), Puerto Rican street dogs, and mixed breed dogs from the United States. Village dogs from most African regions appear genetically distinct from non-native breed and mixed-breed dogs, although some individuals cluster genetically with Puerto Rican dogs or United States breed mixes instead of with neighboring village dogs. Thus, African village dogs are a mosaic of indigenous dogs descended from early migrants to Africa, and non-native, breed-admixed individuals. Among putatively African breeds, Pharaoh hounds, and Rhodesian ridgebacks clustered with non-native rather than indigenous African dogs, suggesting they have predominantly non-African origins. Surprisingly, we find similar mtDNA haplotype diversity in African and East Asian village dogs, potentially calling into question the hypothesis of an East Asian origin for dog domestication. PMID:19666600

  20. Dog and cat bites.

    PubMed

    Ellis, Robert; Ellis, Carrie

    2014-08-15

    Animal bites account for 1% of all emergency department visits in the United States and more than $50 million in health care costs per year. Most animal bites are from a dog, usually one known to the victim. Most dog bite victims are children. Bite wounds should be cleaned, copiously irrigated with normal saline using a 20-mL or larger syringe or a 20-gauge catheter attached to the syringe. The wound should be explored for tendon or bone involvement and possible foreign bodies. Wounds may be closed if cosmetically favorable, such as wounds on the face or gaping wounds. Antibiotic prophylaxis should be considered, especially if there is a high risk of infection, such as with cat bites, with puncture wounds, with wounds to the hand, and in persons who are immunosuppressed. Amoxicillin/clavulanate is the first-line prophylactic antibiotic. The need for rabies prophylaxis should be addressed with any animal bite because even domestic animals are often unvaccinated. Postexposure rabies prophylaxis consists of immune globulin at presentation and vaccination on days 0, 3, 7, and 14. Counseling patients and families about animal safety may help decrease animal bites. In most states, physicians are required by law to report animal bites.

  1. Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk.

    PubMed

    Sumis, Allison; Cook, Katherine L; Andrade, Fabia O; Hu, Rong; Kidney, Emma; Zhang, Xiyuan; Kim, Dominic; Carney, Elissa; Nguyen, Nguyen; Yu, Wei; Bouker, Kerrie B; Cruz, Idalia; Clarke, Robert; Hilakivi-Clarke, Leena

    2016-10-01

    Social isolation is a strong predictor of early all-cause mortality and consistently increases breast cancer risk in both women and animal models. Because social isolation increases body weight, we compared its effects to those caused by a consumption of obesity-inducing diet (OID) in C57BL/6 mice. Social isolation and OID impaired insulin and glucose sensitivity. In socially isolated, OID-fed mice (I-OID), insulin resistance was linked to reduced Pparg expression and increased neuropeptide Y levels, but in group-housed OID fed mice (G-OID), it was linked to increased leptin and reduced adiponectin levels, indicating that the pathways leading to insulin resistance are different. Carcinogen-induced mammary tumorigenesis was significantly higher in I-OID mice than in the other groups, but cancer risk was also increased in socially isolated, control diet-fed mice (I-C) and G-OID mice compared with that in controls. Unfolded protein response (UPR) signaling (GRP78; IRE1) was upregulated in the mammary glands of OID-fed mice, but not in control diet-fed, socially isolated I-C mice. In contrast, expression of BECLIN1, ATG7 and LC3II were increased, and p62 was downregulated by social isolation, indicating increased autophagy. In the mammary glands of socially isolated mice, but not in G-OID mice, mRNA expressions of p53 and the p53-regulated autophagy inducer Dram1 were upregulated, and nuclear p53 staining was strong. Our findings further indicated that autophagy and tumorigenesis were not increased in Atg7(+/-) mice kept in social isolation and fed OID. Thus, social isolation may increase breast cancer risk by inducing autophagy, independent of changes in body weight.

  2. Phylogenetic identification of Cystoisospora spp. from dogs, cats, and raccoon dogs in Japan.

    PubMed

    Matsubayashi, Makoto; Carreno, Ramon A; Tani, Hiroyuki; Yoshiuchi, Ryusaku; Kanai, Takenori; Kimata, Isao; Uni, Shigehiko; Furuya, Masaru; Sasai, Kazumi

    2011-03-10

    Cystoisospora spp. from feces in dogs, cats, and raccoon dogs were isolated, sequenced at the small subunit ribosomal RNA gene locus and compared to other Cystoisospora spp. Cystoisospora oocysts from dogs and raccoon dogs were morphologically similar with those of C. ohioensis, and cat isolates were similar with those of C. felis. The sequences from dogs and raccoon dogs, and cats have a homology with C. ohioensis and C. felis, respectively. Phylogenetic analysis of the DNA sequences showed that the dog and raccoon dog isolates were nested in a clade with other Cystoisospora spp. including C. ohioensis, C. belli, and C. orlovi. The cat isolate formed a sister group with C. felis that was a separate clade from the dog and raccoon dog group. We report sequence variation in these Cystoisospora sequences and have identified raccoon dogs as another carnivore host for Cystoisospora spp. infecting dogs.

  3. Specific posttranslational modification regulates early events in mammary carcinoma formation.

    PubMed

    Guo, Hua-Bei; Johnson, Heather; Randolph, Matthew; Nagy, Tamas; Blalock, Ryan; Pierce, Michael

    2010-12-07

    The expression of an enzyme, GnT-V, that catalyzes a specific posttranslational modification of a family of glycoproteins, namely a branched N-glycan, is transcriptionally up-regulated during breast carcinoma oncogenesis. To determine the molecular basis of how early events in breast carcinoma formation are regulated by GnT-V, we studied both the early stages of mammary tumor formation by using 3D cell culture and a her-2 transgenic mouse mammary tumor model. Overexpression of GnT-V in MCF-10A mammary epithelial cells in 3D culture disrupted acinar morphogenesis with impaired hollow lumen formation, an early characteristic of mammary neoplastic transformation. The disrupted acinar morphogenesis of mammary tumor cells in 3D culture caused by her-2 expression was reversed in tumors that lacked GnT-V expression. Moreover, her-2-induced mammary tumor onset was significantly delayed in the GnT-V null tumors, evidence that the lack of the posttranslational modification catalyzed by GnT-V attenuated tumor formation. Inhibited activation of both PKB and ERK signaling pathways was observed in GnT-V null tumor cells. The proportion of tumor-initiating cells (TICs) in the mammary tumors from GnT-V null mice was significantly reduced compared with controls, and GnT-V null TICs displayed a reduced ability to form secondary tumors in NOD/SCID mice. These results demonstrate that GnT-V expression and its branched glycan products effectively modulate her-2-mediated signaling pathways that, in turn, regulate the relative proportion of tumor initiating cells and the latency of her-2-driven tumor onset.

  4. 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.

  5. Endocrine-active chemicals in mammary cancer causation and prevention.

    PubMed

    Jenkins, Sarah; Betancourt, Angela M; Wang, Jun; Lamartiniere, Coral A

    2012-04-01

    Endocrine-active chemicals alter or mimic physiological hormones. These compounds are reported to originate from a wide variety of sources, and recent studies have shown widespread human exposure to several of these compounds. Given the role of the sex steroid hormone, estradiol, in human breast cancer causation, endocrine-active chemicals which interfere with estrogen signaling constitute one potential factor contributing to the high incidence of breast cancer. Thus, the aim of this review is to examine several common endocrine-active chemicals and their respective roles in breast cancer causation or prevention. The plastic component, bisphenol A (BPA), the synthetic estrogen, diethylstilbestrol (DES), the by-product of organic combustion, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the soy component, genistein, and the red grape phytoalexin, resveratrol, have some degree of structural similarities to each other and estradiol. However, despite these structural similarities, the in vitro and in vivo properties of each of these chemicals vary greatly in terms of breast cancer causation and prevention. Early life exposure to BPA and DES increases rodent susceptibility to chemically induced mammary carcinogenesis, presumably through retardation of normal mammary gland maturation and/or disrupting the ratio of cell proliferation and apoptosis in the mammary gland. On the other hand, early exposures to genistein and resveratrol protect rodents against chemically induced and spontaneous mammary cancers. This is reported to occur through the ability of genistein and resveratrol to accelerate mammary gland maturation. Interestingly, TCDD, which is the most structurally dissimilar to the above chemicals and functions as an anti-estrogen, also increases chemically induced mammary carcinogenesis through retardation of mammary gland maturation. This article is part of a Special Issue entitled 'Endocrine disruptors'.

  6. Metabotropic glutamate receptor 1 disrupts mammary acinar architecture and initiates malignant transformation of mammary epithelial cells

    PubMed Central

    Teh, Jessica L. F.; Shah, Raj; La Cava, Stephanie; Dolfi, Sonia C.; Mehta, Madhura S.; Kongara, Sameera; Price, Sandy; Ganesan, Shridar; Reuhl, Kenneth R.; Hirshfield, Kim M.

    2016-01-01

    Metabotropic glutamate receptor 1 (mGluR1/Grm1) is a member of the G-protein-coupled receptor superfamily, which was once thought to only participate in synaptic transmission and neuronal excitability, but has more recently been implicated in non-neuronal tissue functions. We previously described the oncogenic properties of Grm1 in cultured melanocytes in vitro and in spontaneous melanoma development with 100 % penetrance in vivo. Aberrant mGluR1 expression was detected in 60–80 % of human melanoma cell lines and biopsy samples. As most human cancers are of epithelial origin, we utilized immortalized mouse mammary epithelial cells (iMMECs) as a model system to study the transformative properties of Grm1. We introduced Grm1 into iMMECs and isolated several stable mGluR1-expressing clones. Phenotypic alterations in mammary acinar architecture were assessed using three-dimensional morphogenesis assays. We found that mGluR1-expressing iMMECs exhibited delayed lumen formation in association with decreased central acinar cell death, disrupted cell polarity, and a dramatic increase in the activation of the mitogen-activated protein kinase pathway. Orthotopic implantation of mGluR1-expressing iMMEC clones into mammary fat pads of immunodeficient nude mice resulted in mammary tumor formation in vivo. Persistent mGluR1 expression was required for the maintenance of the tumorigenic phenotypes in vitro and in vivo, as demonstrated by an inducible Grm1-silencing RNA system. Furthermore, mGluR1 was found be expressed in human breast cancer cell lines and breast tumor biopsies. Elevated levels of extracellular glutamate were observed in mGluR1-expressing breast cancer cell lines and concurrent treatment of MCF7 xenografts with glutamate release inhibitor, riluzole, and an AKT inhibitor led to suppression of tumor progression. Our results are likely relevant to human breast cancer, highlighting a putative role of mGluR1 in the pathophysiology of breast cancer and the potential

  7. 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...

  8. Dog pack attack: hunting humans.

    PubMed

    Avis, S P

    1999-09-01

    Dog bite-related fatalities, although unusual, accounted for 304 deaths in the United States between 1979 and 1996 and 6 fatalities in Canada between 1994 and 1996. Fatal dog pack attacks and attacks involving human predation are less common. The following describes a dog pack attack on a family of four involving 2 fatalities with predation of the victims. Factors previously identified that contribute to pack attacks and predation, including prior group hunting, social feeding, territorial defense, lack of human interaction, and prey stimuli, are discussed.

  9. 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

  10. Human chorionic gonadotropin and CA 15-3 producing adenocarcinoma.

    PubMed

    Uçkaya, G; Ozet, A; Arpaci, A; Kömürcü, S

    1998-01-01

    50 years old man suffering from primary lung adenocarcinoma presented with high levels of both beta subunit human chorionic gonadotropin (beta HCG) and cancer antigen 15-3 (CA 15-3) in the absence of elevated carcinoembrionic antigen (CEA), alfa fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9). Although beta HCG or CA 15-3 high levels were reported in adenocarcinoma of lung, this is the first report of a patient with high levels of both markers.

  11. Metachronous Colon Metastases from Gastric Adenocarcinoma: A Case Report

    PubMed Central

    Pace, Ugo; Contino, Gianmarco; Chiappa, Antonio; Bertani, Emilio; Bianchi, Paolo P.; Fazio, Nicola; Renne, Giuseppe; Di Meglio, Giovanni; Andreoni, Bruno

    2009-01-01

    The colon is a very rare metastatic localization. Here we report a case of colonic metastases from gastric adenocarcinoma whose clinical presentation was suggestive of a de novo adenocarcinoma of the ascending colon. The authors discuss that in the presence of a previous history of gastric cancer, immunohistochemical analysis on endoscopic biopsies may help in the definition of a differential diagnosis. Furthermore, this rare metastatic localization might suggest a poor prognosis and a more accurate diagnostic work-up. PMID:20740169

  12. [Gastric signet ring cell adenocarcinoma: A distinct entity].

    PubMed

    Tabouret, Tessa; Dhooge, Marion; Rouquette, Alexandre; Brezault, Catherine; Beuvon, Frédéric; Chaussade, Stanislas; Coriat, Romain

    2014-04-01

    Gastric signet ring cell carcinoma (GSRC) is a distinct entity. Their incidence is increasing. The pathologist plays a central role in the identification of this entity. Diagnosis is based on an adenocarcinoma containing a majority of signet ring cells (above 50 %). The prognosis of GSRC is the same as gastric adenocarcinoma while GSRC appeared more aggressive. Signet ring cells present a low sensitivity to chemotherapy. This review aimed to discuss the histological, the prognostic and the therapeutic aspect of this entity.

  13. [A survey on intestinal parasites of livestock guardian dogs and herding dogs in Switzerland].

    PubMed

    Frey, C F; Regotz, J; Rosenberg, G; Gottstein, B; Kohler, S

    2010-12-01

    The present study describes the occurrence of intestinal parasite infections in livestock guardian dogs and herding dogs. A total of 71 guardian dogs (more than half of the total number of guardian dogs in Switzerland) and 21 herding dogs were coprologically examined, using a combined sedimentation-flotation method. In 21 (23 %) of the dogs intestinal parasites were detected, and 8 (8.7 %) of these dogs shed either sporocysts of Sarcocystis sp. (n = 6) or taeniid eggs (n = 2). The evaluation of questionnaires providing data on age, origin and deworming schemes of the dogs completed the study.

  14. Prevalence of staphylococcal enterotoxins in Staphylococcus pseudintermedius isolates from dogs with pyoderma and healthy dogs.

    PubMed

    Tanabe, Taishi; Toyoguchi, Midori; Hirano, Fumitaka; Chiba, Mei; Onuma, Kenta; Sato, Hisaaki

    2013-09-01

    To investigate the role of staphylococcal enterotoxins (SEs) produced by Staphylococcus pseudintermedius in the pathogenesis of pyoderma, isolates from dogs with pyoderma and healthy dogs were analyzed. According to reverse passive latex agglutination, 14/184 isolates (7.6%) from dogs with pyoderma and 9/87 (10.3%) from healthy dogs produced SEs (SEA, SEC or SED). According to multiplex PCR, 99 isolates (53.7%) from dogs with pyoderma and 97 (90.8%) from healthy dogs possessed one or more se genes. There was no significant difference regarding ses between dogs with pyoderma and healthy dogs. Therefore, SEs may not be a direct virulence factor in pyoderma.

  15. Mammary analogue secretory carcinoma: an evaluation of its clinicopathological and genetic characteristics.

    PubMed

    Luk, Peter P; Selinger, Christina I; Eviston, Timothy J; Lum, Trina; Yu, Bing; O'Toole, Sandra A; Clark, Jonathan R; Gupta, Ruta

    2015-12-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland malignancy. We evaluate the clinicopathological characteristics and long-term clinical behaviour of MASCs. A total of 190 primary salivary gland malignancies at a single institution were reviewed along with relevant immunohistochemical and fluorescent in situ hybridisation (FISH) studies to identify MASCs. Nine MASCs were identified predominantly in the parotid with an equal incidence in men and women and mean age of 36 years. The tumour size ranged from 14 to 50 mm (mean 22 mm). MASCs were composed of monotonous cells with vacuolated eosinophilic cytoplasm and a small nucleus with a distinctive nucleolus. All cases showed immunoreactivity with S-100, MUC4, CK7 and mammoglobin, and lacked immunoreactivity with DOG1, p63, CK5/6 and calponin. ETV6 rearrangement was seen in all cases. No mutations were identified using the OncoCarta Panel v1.0 Kit. Follow up was available for 0.4 to 22 years (median 4 years). Intraparotid lymph node involvement and local recurrence were seen in one patient each. There were no distant metastases. MASCs have specific histopathological features and immunohistochemical profile that distinguish them from their mimics. FISH plays a confirmatory role. An indolent long-term clinical course was observed in this cohort despite involvement of intraparotid lymph node and microscopically involved/close margins.

  16. 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.

  17. Identification of triple-negative and basal-like canine mammary carcinomas using four basal markers.

    PubMed

    Kim, N H; Lim, H Y; Im, K S; Kim, J H; Sur, J-H

    2013-05-01

    Molecular-based classification of canine mammary carcinomas (CMCs) has been a recent research focus. In human breast cancer, triple-negative and basal-like phenotypes are distinct molecular subgroups that are known for their poor prognosis, but these tumours are not yet well defined in the dog. The aim of this study was to determine whether CMCs include triple-negative and basal-like phenotypes by immunohistochemical assessment of expression of the oestrogen receptor (OR), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and four basal markers, cytokeratin (CK) 14, CK5/6, p63 and the epidermal growth factor receptor (EGFR). In this study of 241 CMCs, 45 triple-negative tumours (OR(-), PR(-) and HER2(-)) were identified and this phenotype was associated with an unfavourable prognosis. In these tumours, the expression of CK14, CK5/6 and EGFR was related to clinicopathological parameters, while the expression of p63 was not relevant. The majority of the triple-negative tumours were of the basal-like phenotype, given that 75.6% of them expressed more than two basal markers. However, three of the basal markers were not uniformly expressed; therefore, the proportion of the basal-like phenotype was altered on the basis of the selection of the markers. Although both triple-negative and basal-like phenotypes are distinct entities in CMC, further study is needed to differentiate one from the other.

  18. The Management and Prognostic Prediction of Adenocarcinoma of Appendix

    PubMed Central

    Xie, Xin; Zhou, Zhangjian; Song, Yongchun; Li, Wenhan; Diao, Dongmei; Dang, Chengxue; Zhang, Hao

    2016-01-01

    Malignant tumours of the appendix are quite rare, especially appendiceal adenocarcinomas, which may be difficult to detect preoperatively or intraoperatively. We collected data for 1404 patients with adenocarcinoma of the appendix from the Surveillance, Epidemiology, and End Results Program (SEER) database to explore the potential associations between clinicopathological factors and overall survival. Furthermore, a novel nomogram for predicting prognosis was developed based on our analysis of the SEER data. The nomogram prediction model included seven prognostic factors derived based on different clinical estimates. When compared with the traditional tumour-node-metastasis (TNM) staging system, the nomogram prediction model showed superior discriminatory power (Harrell’s C-index, 0.741 vs. 0.686) and a greater degree of similarity to actual 5-year overall survival after calibration (Akaike Information Criterion index, 5270.781 vs. 5430.141). Finally, we provide recommendations for the management of patients with adenocarcinoma of the appendix. Notably, we found the depth of adenocarcinoma invasion may be used as an indicator to determine the optimal surgical approach. For mucinous adenocarcinomas of the appendix, because these tumours are characterized by unique biological behaviour, intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended. However, whether systematic chemotherapy should be administered to patients with adenocarcinoma of the appendix requires further investigation. PMID:27982068

  19. Windows in early mammary development: critical or not?

    PubMed

    Knight, C H; Sorensen, A

    2001-09-01

    Two critical windows in mammary development have been proposed. The first arises from observations in rodents that nutrition during fetal and neonatal periods can affect mammary ductular outgrowth, subsequent proliferative activity and, eventually, tumorigenesis, that is, potentially it could have a long-term effect on pathological outcome (breast cancer) in women. The second similarly involves early diet, but in this case the outcome is phenotypic, in that dairy heifers reared too quickly during the peripubertal period subsequently show impaired udder development and reduced milk yield persisting throughout life. Most mammary development occurs during pregnancy, but this period is usually thought of only in terms of the immediate outcome for the subsequent lactation; it is not believed to be a critical window, at least in terms of lifetime mammary productivity. This review examines the evidence underlying these various claims and attempts to define the mechanisms involved, and also considers whether derangements occurring earlier in life (prenatally) could also have long-term consequences for physiological or pathological mammary development.

  20. Quantification of progesterone binding in mammary tissue of pregnant ewes

    SciTech Connect

    Smith, J.J.; Capuco, A.V.; Akers, R.M.

    1987-06-01

    Progestin-binding sites in mammary tissue from 14 prepartum, multiparous ewes at 50, 80, 115, and 140 d of gestation were demonstrated by the binding of (/sup 3/H) R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) to ovine mammary cytosol in the presence of sodium molybdate and excess cortisol. Homogenization extracted 89% of total mammary receptors (nuclear) into cytosol. Binding was specific for progestins and was of high affinity. The average dissociation constant for (/sup 3/H) R5020 specifically bound to receptors extracted into mammary cytosol was 1.9 (+/- .4) x 10/sup -9/ M (n = 14) and did not change significantly over the test period. However, binding capacities (fmol/mg cytosolic protein) differed according to stage of gestation with averages of 125 +/- 53, 149 +/- 26, 656 +/- 216, 57 +/- 22 at 50, 80, 115, and 140 d of pregnancy, respectively. Increased number of progestin-binding sites at 115 d of gestation (whether data are expressed per unit of tissue weight, DNA, or cytosolic protein) suggests that an increase per mammary epithelial cell may be necessary to produce the full lobuloalveolar proliferation observed at this stage of gestation.

  1. 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.

  2. Hormonal regulation of the immune microenvironment in the mammary gland.

    PubMed

    Need, Eleanor F; Atashgaran, Vahid; Ingman, Wendy V; Dasari, Pallave

    2014-07-01

    It is well established that the development and homeostasis of the mammary gland are highly dependent upon the actions of ovarian hormones progesterone and estrogen, as well as the availability of prolactin for the pregnant and lactating gland. More recently it has become apparent that immune system cells and cytokines play essential roles in both mammary gland development as well as breast cancer. Here, we review hormonal effects on mammary gland biology during puberty, menstrual cycling, pregnancy, lactation and involution, and dissect how hormonal control of the immune system may contribute to mammary development at each stage via cytokine secretion and recruitment of macrophages, eosinophils, mast cells and lymphocytes. Collectively, these alterations may create an immunotolerant or inflammatory immune environment at specific developmental stages or phases of the menstrual cycle. Of particular interest for further research is investigation of the combinatorial actions of progesterone and estrogen during the luteal phase of the menstrual cycle and key developmental points where the immune system may play an active role both in mammary development as well as in the creation of an immunotolerant environment, thereby affecting breast cancer risk.

  3. Serotonin: a local regulator in the mammary gland epithelium.

    PubMed

    Horseman, Nelson D; Collier, Robert J

    2014-02-01

    Serotonin (5-hydroxytryptamine, 5-HT) is a very simple molecule that plays key roles in complex communication mechanisms within the animal body. In the mammary glands, serotonin biosynthesis and secretion are induced in response to dilation of the alveolar spaces. Since its discovery several years ago, mammary 5-HT has been demonstrated to perform two homeostatic functions. First, serotonin regulates lactation and initiates the transition into the earliest phases of involution. Second, serotonin is a local signal that induces parathyroid hormone-related peptide (PTHrP), which allows the mammary gland to drive the mobilization of calcium from the skeleton. These processes use different receptor types, 5-HT7 and 5-HT2, respectively. In this review, we provide synthetic perspectives on the fundamental processes of lactation homeostasis and the adaptation of calcium homeostasis for lactation. We analyze the role of the intrinsic serotonin system in the physiological regulation of the mammary glands. We also consider the importance of the mammary serotonin system in pathologies and therapies associated with lactation and breast cancer.

  4. 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 ...

  5. 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...

  6. The Analysis of Cell Population Dynamics in Mammary Gland Development and Tumorigenesis

    DTIC Science & Technology

    2006-08-01

    processes of mammary epithelial cell differentiation during developmentand tumorigenesis. Using FACS, mammary epithelial cell ( MEC ) populations from tumors...developed techniques for viral transduction andtransplantation of primary MECs . 15. SUBJECT TERMS mammary, stem cell, lentivirus, FACS, cancer, imaging 16...epithelial cell ( MEC ) populations from tumors and wildtype tissue was investigated for their outgrowth potential or tumorigenic capacity. We also developed

  7. 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 ...

  8. Mammary fibroadenomatous hyperplasia in a young cat attributed to treatment with megestrol acetate

    PubMed Central

    MacDougall, Lori D.

    2003-01-01

    A male, neutered cat was presented for lethargy, reluctance to walk, and mammary enlargement after recent treatment with megestrol acetate. Mammary fibroadenomatous hyperplasia was diagnosed on the basis of history, clinical signs, and histopathological findings. Pathogenesis, clinical signs, and treatment options for mammary fibroadenomatous hyperplasia attributed to megestrol acetate treatment are discussed. PMID:12677692

  9. Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma

    PubMed Central

    Nadolski, Amy C.; Markovich, Jessica E.; Jennings, Samuel H.; Mahony, Orla M.

    2016-01-01

    A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior. PMID:27708447

  10. Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma.

    PubMed

    Nadolski, Amy C; Markovich, Jessica E; Jennings, Samuel H; Mahony, Orla M

    2016-10-01

    A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior.

  11. 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.

  12. Breast cancer detection using mammary ductoscopy.

    PubMed

    Sauter, Edward

    2005-06-01

    Mammary ductoscopy (MD) has been used as a tool to evaluate the breast for cancer for over 10 years. MD allows the direct visualization of the duct lumen, providing a more targeted approach to the diagnosis of disease arising in the ductal system, since the lesion can be visualized and samples collected in the area of interest. Initial studies of MD evaluated women with pathologic spontaneous nipple discharge (PND), while more recent reports are also using MD to assess women without PND for the presence of breast cancer. Cytologic assessment of MD is highly specific but less sensitive in the detection of breast cancer. Nonetheless, a MD sample from a breast with PND may rarely undergo cytologic review and be interpreted as consistent with malignancy, only later to undergo surgical resection demonstrating benign pathology. For this reason, PND specimens interpreted as malignant on cytologic review require histopathologic confirmation prior to instituting therapy. Additional sample evaluation using image or molecular analysis may improve the sensitivity and specificity of MD in breast cancer detection.

  13. Frustration behaviors in domestic dogs.

    PubMed

    Jakovcevic, Adriana; Elgier, Angel M; Mustaca, Alba E; Bentosela, Mariana

    2013-01-01

    During extinction a previously learned behavior stops being reinforced. In addition to the decrease in the rate of the instrumental response, it produces an aversive emotional state known as frustration. This state can be assimilated with the fear reactions that occur after aversive stimuli are introduced at both the physiological and behavioral levels. This study evaluated frustration reactions of domestic dogs (Canis familiaris) during a communicative situation involving interactions with a human. The task included the reinforcement and extinction of the gaze response toward the experimenter's face when the dogs tried to obtain inaccessible food. The dog's frustration reactions during extinction involved an increase in withdrawal and side orientation to the location of the human as well as lying down, ambulation, sniffing, and vocalizations compared with the last acquisition trial. These results are especially relevant for domestic dog training situations in which the extinction technique is commonly used to discourage undesirable behaviors.

  14. Do dogs (Canis familiaris) show contagious yawning?

    PubMed

    Harr, Aimee L; Gilbert, Valerie R; Phillips, Kimberley A

    2009-11-01

    We report an experimental investigation into whether domesticated dogs display contagious yawning. Fifteen dogs were shown video clips of (1) humans and (2) dogs displaying yawns and open-mouth expressions (not yawns) to investigate whether dogs showed contagious yawning to either of these social stimuli. Only one dog performed significantly more yawns during or shortly after viewing yawning videos than to the open-mouth videos, and most of these yawns occurred to the human videos. No dogs showed significantly more yawning to the open-mouth videos (human or dog). The percentage of dogs showing contagious yawning was less than chimpanzees and humans showing this behavior, and considerably less than a recently published report investigating this behavior in dogs (Joly-Mascheroni et al. in Biol Lett 4:446-448, 2008).

  15. Dietary lignin, and insoluble fiber, enhance uterine cancer but did not influence mammary cancer induced by N-methyl-N-nitrosourea in rats.

    PubMed

    Birt, D F; Markin, R S; Blackwood, D; Harvell, D M; Shull, J D; Pennington, K L

    1998-01-01

    Previous investigations suggested potential breast cancer-preventive properties of dietary fiber from cabbage. The purpose of the present investigation was to determine whether lignin, a component of cabbage fiber, would protect against mammary carcinogenesis by N-methyl-N-nitrosourea (MNU) in Sprague-Dawley rats. A six-week study was conducted using diets containing 0.5-5% dietary wood lignin (a readily available, purified source). These diets were well tolerated by the rats, and a carcinogenesis study using 5 mg MNU/100 g body wt i.v. at 50 days of age was conducted, with the 2.5% lignin diet fed from 6 through 8 weeks of age followed by 5% lignin diet until 20 weeks after MNU. Dietary lignin and MNU treatment increased food consumption (p < 0.05), and body weight was slightly reduced at 10 and 20 weeks after MNU in the MNU-5% lignin diet group (p < 0.05). Serum estradiol was not altered by dietary lignin or MNU treatment, but uterine weights were highest in the MNU-control diet group 4 and 12 weeks after MNU. Expression of creatine kinase B, and estrogen-responsive gene, was lower in eh uteri of the MNU-lignin diet group than in other groups at 20 weeks. Mammary carcinogenesis was not altered by dietary lignin. However, uterine endometrial adenocarcinoma was observed only in the MNU-lignin diet group (4 carcinomas/40 effective rats) (p < 0.05).

  16. Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin.

    PubMed

    Park, Won Young; Kim, Mi Hyun; Shin, Dong Hoon; Lee, Jung Hee; Choi, Kyung Un; Kim, Jee Yeon; Park, Do Youn; Lee, Chang Hun; Sol, Mee Young

    2012-09-01

    Whereas most carcinomas occur through a sequential step, atypical adenomatous hyperplasia and bronchioloalveolar carcinoma pathway is known for pulmonary adenocarcinoma. This type is known as terminal respiratory unit adenocarcinoma. Based on our observation of transitions from normal ciliated columnar cells to adenocarcinoma via dysplastic mucous columnar cells, we reviewed our archive of pulmonary adenocarcinoma. Terminal respiratory unit type adenocarcinoma was defined as adenocarcinoma with type II pneumocyte, Clara cell, or bronchiolar cell morphology according to previous reports. Among 157 cases, 121 cases have been identified as terminal respiratory unit type adenocarcinoma and 36 cases as non-terminal respiratory unit type adenocarcinoma. Among non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma.

  17. Hepatoid adenocarcinoma of the stomach – a different histology for not so different gastric adenocarcinoma: a case report

    PubMed Central

    Gálvez-Muñoz, Elisa; Gallego-Plazas, Javier; Gonzalez-Orozco, Verónica; Menarguez-Pina, Francisco; Ruiz-Maciá, José A; Morcillo, Miguel A

    2009-01-01

    Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. Hepatoid adenocarcinoma of the stomach is a cancer with an extremely poor prognosis with few cases reported. Here, we describe a 75-year-old Spanish man referred to our hospital with a history of abdominal pain, general fatigue, anorexia and sickness. Initial study revealed anemia, and computed tomography scan and abdominal ultrasonography showed multiple metastases to the liver with hepatocellular carcinoma characteristics in a liver with no cirrhotic change. Further study included a serum level of alpha-fetoprotein (AFP), which resulted markedly elevated, and a conclusive esophagogastroduodenoscopy describing an elevated tumour growing through the cardia and gastroesophageal junction with foci of necrosis and haemorrhage. Gastric biopsies of the tumor revealed poorly differenciated adenocarcinoma, with hepatoid differentiation. After a diagnosis of AFP-producing hepatoid adenocarcinoma of the stomach with multiple liver metastases was made, pallitive total gastrectomy, without liver resection, was performed. Patient recovered well after surgery, and entered into a palliative systemich chemotherapy protocol. Although this illness is recognized as having poor prognosis, the patient remains alive 8 months after the operation. Accurate diagnosis of hepatoid adenocarcinoma of the stomach is important, and should be suspected under certain circumstances. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects. PMID:19674468

  18. Int-6, a highly conserved, widely expressed gene, is mutated by mouse mammary tumor virus in mammary preneoplasia.

    PubMed Central

    Marchetti, A; Buttitta, F; Miyazaki, S; Gallahan, D; Smith, G H; Callahan, R

    1995-01-01

    With a unique mouse mammary tumor model system in which mouse mammary tumor virus (MMTV) insertional mutations can be detected during progression from preneoplasia to frank malignancy, including metastasis, we have discovered a new common integration site (designated Int-6) for MMTV in mouse mammary tumors. MMTV was integrated into Int-6 in a mammary hyperplastic outgrowth line, its tumors and metastases, and two independent mammary tumors arising in unrelated mice. The Int-6 gene is ubiquitously expressed as a 1.4-kb RNA species in adult tissues and is detected beginning at day 8 of embryonic development. The nucleotide sequence of Int-6 is unrelated to any of the known genes in the GenBank database. MMTV integrates within introns of the gene in the opposite transcriptional orientation. In each tumor tested, this results in the expression of a truncated Int-6/long terminal repeat (LTR) chimeric RNA species which is terminated at a cryptic termination signal in the MMTV LTR. Since the nonrearranged Int-6 alleles in these tumors contain no mutations, we favor the conclusion that truncation of the Int-6 gene product either biologically activates its function or represents a dominant-negative mutation. PMID:7853537

  19. 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.

  20. Service Dogs in the Perioperative Setting.

    PubMed

    Levey, Janet A; Chappy, Sharon L

    2017-04-01

    Service dogs are critical for the independence of individuals with disabilities because they assist with daily living activities and help these individuals navigate society. Perioperative nurses need a working knowledge of disability laws pertaining to service dogs to provide patient-centered care for individuals using service dogs. This article provides information on the Americans With Disabilities Act regulations regarding service dogs, makes recommendations for the care of patients with service dogs across the perioperative continuum, and offers policy directives to ensure that safe, high-quality care is delivered to patients using service dogs.

  1. Annexin A3 Knockdown Suppresses Lung Adenocarcinoma

    PubMed Central

    Liu, Qing-Qing; Zhang, Yue-Hua; Qiu, Jing-Hua

    2016-01-01

    Our previous study identified an elevated abundance of annexin A3 (Anxa3) as a novel prognostic biomarker of lung adenocarcinoma (LADC) through quantitative proteomics analysis. However, the biological functions of Anxa3 in LADC are not fully clear. In this study, in vitro and in vivo assays were performed to investigate the effects of Anxa3 downregulation on the growth, migration, invasion, metastasis, and signaling pathway activation of LADC cells. After Anxa3 downregulation, the growth of A549 and LTEP-a2 LADC cells was slowed and they showed decreased migration and invasion in vitro. Anxa3 knockdown significantly inhibited tumor formation by A549 cells in vivo; while many metastases were formed by control A549 cells, there were obvious reductions in the numbers of lung, liver, and brain metastases formed by Anxa3 knockdown in A549 cells. Furthermore, Anxa3 knockdown significantly decreased MMP-2 and N-cadherin expression and increased E-cadherin expression both in cell lines in vitro and in tumor nodules examined during in vivo tumorigenesis assays. Interestingly, Anxa3 downregulation reduced the phosphorylated levels of MEK and ERK. In summary, Anxa3 knockdown inhibited the growth, migration, invasion, and metastasis of LADC, decreased the activation of the MEK/ERK signaling pathway, and modulated the expression of MMP-2, E-cadherin, and N-cadherin. PMID:27995049

  2. Pancreatic adenocarcinoma pathology: changing “landscape”

    PubMed Central

    Brosens, Lodewijk A. A.; Hackeng, Wenzel M.; Offerhaus, G. Johan; Hruban, Ralph H.

    2015-01-01

    Pancreatic cancer is a devastating disease. At time of diagnosis the disease is usually advanced and only a minority of patients are eligible for surgical resection. The overall 5-year survival is 6%. However, survival of patients with early stage pancreatic cancer is significantly better. To improve the prognosis of patients with pancreatic cancer, it is essential to diagnose and treat pancreatic cancer in the earliest stage. Prevention of pancreatic cancer by treating noninvasive precursor lesions just before they invade tissues can potentially lead to even better outcomes. Pancreatic carcinogenesis results from a stepwise progression in which accumulating genetic alterations drive neoplastic progression in well-defined precursor lesions, ultimately giving rise to an invasive adenocarcinoma. A thorough understanding of the genetic changes that drive pancreatic carcinogenesis can lead to identification of biomarkers for early detection and targets for therapy. Recent next-generation sequencing (NGS) studies have shed new light on our understanding of the natural history of pancreatic cancer and the precursor lesions that give rise to these cancers. Importantly, there is a significant window of opportunity for early detection and treatment between the first genetic alteration in a cell in the pancreas and development of full-blown pancreatic cancer. The current views on the pathology and genetics of pancreatic carcinogenesis that evolved from studies of pancreatic cancer and its precursor lesions are discussed in this review. PMID:26261723

  3. Emerging therapeutic targets in esophageal adenocarcinoma

    PubMed Central

    Gaur, Puja; Hunt, Clayton R.; Pandita, Tej K.

    2016-01-01

    The incidence of gastro-esophageal disease and associated rate of esophageal adenocarcinoma (EAC) is rising at an exponential rate in the United States. However, research targeting EAC is lagging behind, and much research is needed in the field to identify ways to diagnose EAC early as well as to improve the rate of pathologic complete response (pCR) to systemic therapies. Esophagectomy with subsequent reconstruction is known to be a morbid procedure that significantly impacts a patient's quality of life. If indeed the pCR rate of patients can be improved and those patients destined to be pCR can be identified ahead of time, they may be able to avoid this life-altering procedure. While cancer-specific biological pathways have been thoroughly investigated in other solid malignancies, much remains unexplored in EAC. In this review, we will highlight some of the latest research in the field in regards with EAC, along with new therapeutic targets that are currently being explored. After reviewing conventional treatment and current changes in medical therapy for EAC, we will focus on unchartered grounds such as cancer stem cells, genetics and epigenetics, immunotherapy, and chemoradio-resistant pathways as we simultaneously propose some investigational possibilities that could be applicable to EAC. PMID:27102294

  4. Algenpantucel-L immunotherapy in pancreatic adenocarcinoma.

    PubMed

    Coveler, Andrew L; Rossi, Gabriela R; Vahanian, Nicholas N; Link, Charles; Chiorean, E Gabriela

    2016-02-01

    Pancreatic adenocarcinoma is the 4th leading cause of cancer death in the USA and the EU. A minority of patients presents with surgically resectable and potentially curable disease, but among these, 80% are destined to relapse and overall survival rates with adjuvant chemotherapy average 24 months. Immunotherapy is a promising therapeutic option and a potential paradigm shift in the treatment of patients with pancreatic cancer, and may be particularly effective when used early in the disease course to prevent metastatic spread. Algenpantucel-L (HyperAcute Pancreas, NewLink Genetics, Ames, IA, USA) is a whole-cell immunotherapy consisting of irradiated allogeneic pancreatic cancer cells genetically engineered to express the murine enzyme α-GT, which results in hyperacute rejection of the tumor cells with complement- and antibody-dependent cytotoxicity. Phase II clinical trial data has been encouraging, particularly for patients who demonstrated humoral immunologic responses. Here, we report preliminary results and biomarkers correlations with clinical activity of algenpantucel-L in pancreatic cancer.

  5. Biology and treatment of cervical adenocarcinoma

    PubMed Central

    Takeuchi, Satoshi

    2016-01-01

    Uterine cervical adenocarcinoma (ADC) has been increasing in its prevalence world widely despite the decrease of squamous cell carcinoma (SCC). It comprises nearly 20-25% of the all cervical malignancy in developed countries. The worse biological behavior had been reported in patients with intermediate- and high risk factors after surgery, and in advanced stage over Ⅲ, radiotherapy (RT) alone and concurrent chemo-radiotherapy (CCRT) with cisplatin was not always effective. As for chemotherapy (CT), the induction CT has not established, as well. Further molecular targeted therapy (MTT) has been studied. The targets of oncogenic driver mutations were vascular endothelial growth factor (VEGF) in SCC, or tyrosine kinase (TK) of endothelial growth factor receptor 2 (EGFR2, Her2/neu)-Ras-MAPK-ERK pathway. Bevacizumab (Bev, anti-VEGF monoclonal antibody) is considered as one of key agent with paclitaxel and carboplatin in SCC, but not for ADC. This article focuses on up-to-date knowledge of biology and possible specific therapeutic directions to explore in the management of cervical ADC. PMID:27198186

  6. Comprehensive molecular characterization of gastric adenocarcinoma

    PubMed Central

    Bass, Adam J.; Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M.; Miller, Michael; Bernard, Brady; Hinoue, Toshinori; Laird, Peter W.; Curtis, Christina; Shen, Hui; Weisenberger, Daniel J.; Schultz, Nikolaus; Shen, Ronglai; Weinhold, Nils; Kelsen, David P.; Bowlby, Reanne; Chu, Andy; Kasaian, Katayoon; Mungall, Andrew J.; Robertson, A. Gordon; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B.; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Parfenov, Michael; Gulley, Margaret; Piazuelo, M. Blanca; Schneider, Barbara G.; Kim, Jihun; Boussioutas, Alex; Sheth, Margi; Demchok, John A.; Rabkin, Charles S.; Willis, Joseph E.; Ng, Sam; Garman, Katherine; Beer, David G.; Pennathur, Arjun; Raphael, Benjamin J.; Wu, Hsin-Ta; Odze, Robert; Kim, Hark K.; Bowen, Jay; Leraas, Kristen M.; Lichtenberg, Tara M.; Weaver, Stephanie; McLellan, Michael; Wiznerowicz, Maciej; Sakai, Ryo; Getz, Gad; Sougnez, Carrie; Lawrence, Michael S.; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric S.; Ding, Li; Niu, Beifang; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chu, Andy; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Nip, Ka Ming; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Beroukhim, Rameen; Carter, Scott L.; Cherniack, Andrew D.; Cho, Juok; Cibulskis, Kristian; DiCara, Daniel; Frazer, Scott; Fisher, Sheila; Gabriel, Stacey B.; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lander, Eric S.; Lawrence, Michael S.; Lichtenstein, Lee; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Sougnez, Carrie; Stojanov, Petar; Tabak, Barbara; Taylor-Weiner, Amaro; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Protopopov, Alexei; Santoso, Netty; Parfenov, Michael; Lee, Semin; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Xi, Ruibin; Bristow, Christopher A.; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Kim, Sang-Bae; Lee, Ju-Seog; Lu, Yiling; Mills, Gordon; Laird, Peter W.; Hinoue, Toshinori; Weisenberger, Daniel J.; Bootwalla, Moiz S.; Lai, Phillip H.; Shen, Hui; Triche, Timothy; Van Den Berg, David J.; Baylin, Stephen B.; Herman, James G.; Getz, Gad; Chin, Lynda; Liu, Yingchun; Murray, Bradley A.; Noble, Michael S.; Askoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, S. Onur; Sun, Yichao; Weinhold, Nils; Thorsson, Vésteinn; Bernard, Brady; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Miller, Michael; Reynolds, Sheila M.; Rovira, Hector; Tasman, Natalie; Shmulevich, Ilya; Ng, Santa Cruz Sam; Haussler, David; Stuart, Josh M.; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Verhaak, Roeland G.W.; Mills, Gordon B.; Leiserson, Mark D. M.; Raphael, Benjamin J.; Wu, Hsin-Ta; Taylor, Barry S.; Black, Aaron D.; Bowen, Jay; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; Leraas, Kristen M.; Lichtenberg, Tara M.; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik; Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Benz, Christopher; Lee, Jae-Hyuk; Fedosenko, Konstantin; Manikhas, Georgy; Potapova, Olga; Voronina, Olga; Belyaev, Smitry; Dolzhansky, Oleg; Rathmell, W. Kimryn; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; ŁaŸniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychała, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Wiznerowicz, Maciej; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young; Penny, Robert; Gardner, Johanna; Kemkes, Ariane; Mallery, David; Morris, Scott; Shelton, Troy; Shelton, Candace; Curley, Erin; Alexopoulou, Iakovina; Engel, Jay; Bartlett, John; Albert, Monique; Park, Do-Youn; Dhir, Rajiv; Luketich, James; Landreneau, Rodney; Janjigian, Yelena Y.; Kelsen, David P.; Cho, Eunjung; Ladanyi, Marc; Tang, Laura; McCall, Shannon J.; Park, Young S.; Cheong, Jae-Ho; Ajani, Jaffer; Camargo, M. Constanza; Alonso, Shelley; Ayala, Brenda; Jensen, Mark A.; Pihl, Todd; Raman, Rohini; Walton, Jessica; Wan, Yunhu; Demchok, John A.; Eley, Greg; Mills Shaw, Kenna R.; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Davidsen, Tanja; Hutter, Carolyn M.; Sofia, Heidi J.; Burton, Robert; Chudamani, Sudha; Liu, Jia

    2014-01-01

    Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. PMID:25079317

  7. Interventional Nanotheranostics of Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Li, Junjie; Liu, Fengyong; Gupta, Sanjay; Li, Chun

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of all pancreatic cancer. Nanoparticles (NPs) offer new opportunities for image-guided therapy owing to the unique physicochemical properties of the nanoscale effect and the multifunctional capabilities of NPs. However, major obstacles exist for NP-mediated cancer theranostics, especially in PDAC. The hypovascular nature of PDAC may impede the deposition of NPs into the tumor after systemic administration, and most NPs localize predominantly in the mononuclear phagocytic system, leading to a relatively poor tumor-to-surrounding-organ uptake ratio. Image guidance combined with minimally invasive interventional procedures may help circumvent these barriers to poor drug delivery of NPs in PDAC. Interventional treatments allow regional drug delivery, targeted vascular embolization, direct tumor ablation, and the possibility of disrupting the stromal barrier of PDAC. Interventional treatments also have potentially fewer complications, faster recovery, and lower cost compared with conventional therapies. This work is an overview of current image-guided interventional cancer nanotheranostics with specific attention given to their applications for the management of PDAC. PMID:27375787

  8. Biology of glucose transport in the mammary gland.

    PubMed

    Zhao, Feng-Qi

    2014-03-01

    Glucose is the major precursor of lactose, which is synthesized in Golgi vesicles of mammary secretory alveolar epithelial cells during lactation. Glucose is taken up by mammary epithelial cells through a passive, facilitative process, which is driven by the downward glucose concentration gradient across the plasma membrane. This process is mediated by facilitative glucose transporters (GLUTs), of which there are 14 known isoforms. Mammary glands mainly express GLUT1 and GLUT8, and GLUT1 is the predominant isoform with a Km of ~10 mM and transport activity for mannose and galactose in addition to glucose. Mammary glucose transport activity increases dramatically from the virgin state to the lactation state, with a concomitant increase in GLUT expression. The increased GLUT expression during lactogenesis is not stimulated by the accepted lactogenic hormones. New evidence indicates that a possible low oxygen tension resulting from increased metabolic rate and oxygen consumption may play a major role in stimulating glucose uptake and GLUT1 expression in mammary epithelial cells during lactogenesis. In addition to its primary presence on the plasma membrane, GLUT1 is also expressed on the Golgi membrane of mammary epithelial cells and is likely involved in facilitating the uptake of glucose and galactose to the site of lactose synthesis. Because lactose synthesis dictates milk volume, regulation of GLUT expression and trafficking represents potentially fruitful areas for further research in dairy production. In addition, this research will have pathological implications for the treatment of breast cancer because glucose uptake and GLUT expression are up-regulated in breast cancer cells to accommodate the increased glucose need.

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. Mammary gland development: cell fate specification, stem cells and the microenvironment.

    PubMed

    Inman, Jamie L; Robertson, Claire; Mott, Joni D; Bissell, Mina J

    2015-03-15

    The development of the mammary gland is unique: the final stages of development occur postnatally at puberty under the influence of hormonal cues. Furthermore, during the life of the female, the mammary gland can undergo many rounds of expansion and proliferation. The mammary gland thus provides an excellent model for studying the 'stem/progenitor' cells that allow this repeated expansion and renewal. In this Review, we provide an overview of the different cell types that constitute the mammary gland, and discuss how these cell types arise and differentiate. As cellular differentiation cannot occur without proper signals, we also describe how the tissue microenvironment influences mammary gland development.

  14. 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.

  15. The contribution of growth hormone to mammary neoplasia

    PubMed Central

    Perry, Jo K; Mohankumar, Kumarasamypet M; Emerald, B Starling; Mertani, Hichem C; Lobie, Peter E

    2008-01-01

    While the effects of growth hormone (GH) on longitudinal growth are well established, the observation that GH contributes to neoplastic progression is more recent. Accumulating literature implicates GH-mediated signal transduction in the development and progression of a wide range malignancies including breast cancer. Recently autocrine human GH been demonstrated to be an orthotopically expressed oncogene for the human mammary gland. This review will highlight recent evidence linking GH and mammary carcinoma and discuss GH-antagonism as a potential therapeutic approach for treatment of breast cancer. PMID:18253708

  16. 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.

  17. Mammary analogue secretory carcinoma of salivary glands: a new entity associated with ETV6 gene rearrangement.

    PubMed

    Majewska, Hanna; Skálová, Alena; Stodulski, Dominik; Klimková, Adéla; Steiner, Petr; Stankiewicz, Czesław; Biernat, Wojciech

    2015-03-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumour that harbours the recurrent ETV6-NTRK3 translocation. This is the first series of MASC cases identified in the historic cohort of carcinomas of salivary glands with clinical/pathological correlation and follow-up data. We reviewed 183 primary carcinomas of major and minor salivary glands resected at the Medical University of Gdańsk, Poland, between 1992 and 2012. Based on morphology and immunohistochemistry, cases suspicious for MASC were selected, and the diagnosis was confirmed by fluorescence in situ hybridization (FISH) for ETV6 rearrangement and by RT-PCR for the ETV6-NTRK3 fusion transcript. Seven carcinomas met the criteria of MASC, as they exhibited a typical appearance with solid/microcystic and papillary architecture and intraluminal secretions, and cells completely devoid of basophilic cytoplasmic zymogen granules indicative of true acinar differentiation. The only paediatric case was an unencapsulated tumour composed of macrocystic structures covered by a mostly single but, focally, double layer of cells with apocrine morphology. In all cases, the neoplastic cells revealed immunoreactivity for S100, mammaglobin, cytokeratin CK7, CK8, STAT5a and vimentin. FISH for ETV6 gene rearrangement was positive in six out of seven cases, and RT-PCR was positive in three cases. MASC is a new entity of malignant epithelial salivary gland tumours not included in the 2005 WHO Classification of Head and Neck Tumours. There is a growing body of evidence that it is not as rare as was assumed, as is also indicated by our series (3.8 %). In most cases, MASC shares some microscopic features with AciCC, adenocarcinoma/cystadenocarcinoma NOS and low-grade MEC. In rare cases, MASC with high-grade transformation may mimic the morphological appearances of high-grade salivary gland malignancies, such as salivary duct carcinoma.

  18. Mammary analogue secretory carcinoma (MASC) of salivary gland in four Mexican patients.

    PubMed

    Serrano-Arévalo, Mónica L; 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.

  19. 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.

  20. Activation of p21(CIP1/WAF1) in mammary epithelium accelerates mammary tumorigenesis and promotes lung metastasis.

    PubMed

    Cheng, Xiaoyun; Xia, Weiya; Yang, Jer-Yen; Hsu, Jennifer L; Chou, Chao-Kai; Sun, Hui-Lung; Wyszomierski, Shannon L; Mills, Gordon B; Muller, William J; Yu, Dihua; Hung, Mien-Chie

    2010-12-03

    While p21 is well known to inhibit cyclin-CDK activity in the nucleus and it has also been demonstrated to have oncogenic properties in different types of human cancers. In vitro studies showed that the oncogenic function of p21is closely related to its cytoplasmic localization. However, it is unclear whether cytoplasmic p21 contributes to tumorigenesis in vivo. To address this question, we generated transgenic mice expressing the Akt-phosphorylated form of p21 (p21T145D) in the mammary epithelium. The results showed that Akt-activated p21 was expressed in the cytoplasm of mammary epithelium. Overexpression of Akt-activated p21 accelerated tumor onset and promoted lung metastasis in MMTV/neu mice, providing evidence that p21, especially cytoplasmic phosphorylated p21, has an oncogenic role in promoting mammary tumorigenesis and metastasis.

  1. [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

  2. Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors.

    PubMed

    Raposo-Ferreira, T M M; Bueno, R C; Terra, E M; Avante, M L; Tinucci-Costa, M; Carvalho, M; Cassali, G D; Linde, S D; Rogatto, S R; Laufer-Amorim, R

    2016-11-01

    The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in normal mammary gland samples (n = 10), benign mammary tumors (n = 11), nonmetastatic mammary carcinomas (n = 19), and metastatic mammary carcinomas (n = 11). Lower ATM transcript levels were detected in benign mammary tumors and carcinomas compared with normal mammary glands (P = .011). Similarly, lower ATM protein expression was observed in benign tumors (P = .0003), nonmetastatic mammary carcinomas (P < .0001), and the primary sites of metastatic carcinomas (P < .0001) compared with normal mammary glands. No significant differences in ATM gene or protein levels were detected among benign tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein downregulation is involved in canine mammary gland tumorigenesis.

  3. The male mammary gland: a target for the xenoestrogen bisphenol A.

    PubMed

    Vandenberg, Laura N; Schaeberle, Cheryl M; Rubin, Beverly S; Sonnenschein, Carlos; Soto, Ana M

    2013-06-01

    Males of some strains of mice retain their mammary epithelium even in the absence of nipples. Here, we have characterized the mammary gland in male CD-1 mice both in whole mounts and histological sections. We also examined the effects of bisphenol A (BPA), an estrogen mimic that alters development of the female mouse mammary gland. BPA was administered at a range of environmentally relevant doses (0.25-250μg/kg/day) to pregnant and lactating mice and then the mammary glands of male offspring were examined at several periods in adulthood. We observed age- and dose-specific effects on mammary gland morphology, indicating that perinatal BPA exposures alter the male mammary gland in adulthood. These results may provide insight into gynecomastia, the most common male breast disease in humans, where proliferation of the mammary epithelium leads to breast enlargement.

  4. 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.

  5. "I'm Just a'-Walking the Dog" correlates of regular dog walking.

    PubMed

    Christian nee Cutt, Hayley; Giles-Corti, Billie; Knuiman, Matthew

    2010-01-01

    Intrapersonal and environmental factors associated with dog walking (N = 483) were examined. A greater proportion of regular (80%) than irregular (59%) dog walkers met the recommended 150 minutes of physical activity per week. Owners who perceived greater social support and motivation from their dogs to walk, and who had access to a dog-supportive park within their neighborhood, were more likely to regularly walk with their dogs, even after adjustment for other well-known correlates of physical activity. The higher level of physical activity of regular dog walkers can be attributed to the additional walking these owners perform with their dogs.

  6. Relationship Between Scarring and Dog Aggression in Pit Bull-Type Dogs Involved in Organized Dogfighting

    PubMed Central

    Miller, Katherine A.; Touroo, Rachel; Spain, C. Victor; Jones, Kelly; Reid, Pamela; Lockwood, Randall

    2016-01-01

    Simple Summary Organizations responsible for placing dogs seized from dogfighting investigations often must determine if a particular dog should be euthanized because it is too dangerous or if it is safe to place the dog in an adoptive home. In this study, we examine whether the extent of scarring from dog fighting is a reliable predictor of aggression towards other dogs and therefore could be used to help make that decision. We found that dogs with 10 or more scars in the three body zones where dogfighting injuries tend to be concentrated were more likely, on average, to show aggression to other dogs. The relationship is imperfect, however. Many unscarred dogs were dog aggressive while some highly scarred dogs were not. Therefore, we recommend also assessing a dog’s behavior before making decisions about its disposition. Abstract When pit bull-type dogs are seized in an investigation of organized dogfighting, heavily scarred dogs are often assumed to be highly dog aggressive due to a history of fighting. These dogs may be deemed dangerous and euthanized based on scarring alone. We analyzed our existing data on dogs seized from four dogfighting investigations, examining the relationship between the dogs’ scars with aggression towards other dogs. Scar and wound data were tallied in three body zones where dogfighting injuries tend to be concentrated. Dog aggression was assessed using a model dog and a friendly stimulus dog in a standardized behavior evaluation. Scarring and dog aggression were significantly related, more strongly among male (Fisher’s Exact p < 0.001) than female dogs (Fisher’s Exact p = 0.05). Ten or more scars in the three body zones was a reasonable threshold with which to classify a dog as high risk for dog aggression: 82% of males and 60% of females with such scarring displayed dog aggression. However, because many unscarred dogs were dog aggressive while some highly scarred dogs were not, we recommend collecting behavioral information to

  7. 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)

  8. Prevention and treatment of dog bites.

    PubMed

    Presutti, R J

    2001-04-15

    Almost one half of all dog bites involve an animal owned by the victim's family or neighbors. A large percentage of dog bite victims are children. Although some breeds of dogs have been identified as being more aggressive than other breeds, any dog may attack when threatened. All dog bites carry a risk of infection, but immediate copious irrigation can significantly decrease that risk. Assessment for the risk of tetanus and rabies virus infection, and subsequent selection of prophylactic antibiotics, are essential in the management of dog bites. The dog bite injury should be documented with photographs and diagrams when appropriate. Family physicians should educate parents and children on ways to prevent dog bites.

  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. Multigene deletions in lung adenocarcinomas from irradiated and control mice

    SciTech Connect

    Zhang, Y.; Woloschak, G.E.

    1996-06-01

    K-ras codon 12 point mutations mRb and p53 gene deletions were examined in tissues from 120 normal lungs and lung adenocarcinomas that were Formalin-treated and paraffin-embedded 25 years ago. The results showed that 12 of 60 (20%) lung adenocarcinomas had mRb deletions. All lung adenocarcinomas that were initially found bearing deleted mRb had p53 deletions (15 of 15; 100%). A significantly higher mutation frequency for K-ras codon 12 point mutations was also found in the lung adenocarcinomas from mice exposed to 24 once-weekly neutron irradiation (10 of 10; 100%) compared with those exposed to 24 or 60 once-weekly {gamma}-ray doses (5 of 10; 50%). The data suggested that p53 and K-ras gene alterations were two contributory factors responsible for the increased incidence of lung adenocarcinoma in B6CF{sub 1} male mice exposed to protracted neutron radiation.

  11. Small bowel adenocarcinomas--existing evidence and evolving paradigms.

    PubMed

    Raghav, Kanwal; Overman, Michael J

    2013-09-01

    Small bowel cancers account for 3% of all gastrointestinal malignancies and small bowel adenocarcinomas represent a third of all small bowel cancers. Rarity of small bowel adenocarcinomas restricts molecular understanding and presents unique diagnostic and therapeutic challenges. Better cross-sectional imaging techniques and development of enteroscopy and capsule endoscopy have facilitated earlier and more-accurate diagnosis. Surgical resection remains the mainstay of therapy for locoregional disease. In the metastatic setting, fluoropyrimidine and oxaliplatin-based chemotherapy has shown clinical benefit in prospective non-randomized trials. Although frequently grouped under the same therapeutic umbrella as large bowel adenocarcinomas, small bowel adenocarcinomas are distinct clinical and molecular entities. Recent progress in molecular characterization has aided our understanding of the pathogenesis of these tumours and holds potential for prospective development of novel targeted therapies. Multi-institutional collaborative efforts directed towards cogent understanding of tumour biology and designing sensible clinical trials are essential for developing improved therapeutic strategies. In this Review, we endeavour to outline an evidence-based approach to present-day management of small bowel adenocarcinoma, describe contemporary challenges and uncover evolving paradigms in the management of these rare 'orphan' neoplasias.

  12. Synchronous Multiple Lung Adenocarcinomas: Estrogen Concentration in Peripheral Lung

    PubMed Central

    Shinchi, Yusuke; Sanada, Mune; Motooka, Yamato; Fujino, Kosuke; Mori, Takeshi; Suzuki, Makoto

    2016-01-01

    Background The detection rate of synchronous multiple lung adenocarcinomas (SMLA), which display multiple ground glass opacity nodules in the peripheral lung, is increasing due to advances in high resolution computed tomography. The backgrounds of multicentric development of adenocarcinoma are unknown. In this study, we quantitated estrogen concentration in the peripheral lungs of postmenopausal female patients with SMLA. Methods The tissue concentration of estrogens (estrone [E1] and estdadiol [E2]) in the noncancerous peripheral lung were measured with liquid chromatography/electrospray tandem mass spectrometry in postmenopausal female patients with lung adenocarcinoma. The expression levels of CYP19A1 in the normal lung were also quantitated with real-time PCR. Thirty patients with SMLA and 79 cases of control patients with single lung adenocarcinoma were analyzed. Results The concentrations of E1 and E2 in the noncancerous tissue were significantly higher in SMLA cases than control cases (P = 0.004 and P = 0.02, respectively). The minor allele (A) of single nucleotide polymorphism rs3764221 were significantly associated with higher concentration of E1 and E2 (P = 0.002 and P = 0.01, respectively) and higher CYP19A1 mRNA expression (P = 0.03). Conclusion The tissue estrogen concentration of peripheral lung was significantly higher in SMLA than control cases. The high concentration of estrogen may be one of the causes of multicentric development of peripheral lung adenocarcinomas. PMID:27526096

  13. Gli promotes epithelial-mesenchymal transition in human lung adenocarcinomas

    PubMed Central

    Jin, Joy Q.; Woodard, Gavitt A.; Tolani, Bhairavi; Luh, Thomas M.; Giroux-Leprieur, Etienne; Mo, Minli; Chen, Zhao; Che, Juanjuan; Zhang, Zhenfa; Zhou, Yong; Wang, Lei; Hao, Xishan; Jablons, David; Wang, Changli; He, Biao

    2016-01-01

    Adenocarcinoma is the most common type of lung cancer. Epithelial-mesenchymal transition (EMT) is required for tumor invasion/metastasis and the components that control this process are potential therapeutic targets. This study we examined the role of Gli in lung adenocarcinoma and whether its activation regulates metastasis through EMT in lung adenocarcinoma. We found that tumors with high Gli expression had significantly lower E-Cadherin expression in two independent cohorts of patients with lung adenocarcinoma that we studied. In vitro up-regulation of SHh resulted in increased cell migration while small molecule inhibitors of Smo or Gli significantly reduced cell mobility both in a wound healing assay and in a 3D cell invasion assay. Inhibition of Gli in vivo decreased tumor growth and induced an increase in E-Cadherin expression. Our results indicate that Gli may be critical for lung adenocarcinoma metastasis and that a novel Gli inhibitor shows promise as a therapeutic agent by preventing cell migration and invasion in vitro and significantly reducing tumor growth and increasing E-Cadherin expression in vivo. PMID:27533453

  14. ATM protein is deficient in over 40% of lung adenocarcinomas.

    PubMed

    Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J

    2016-09-06

    Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

  15. Intestinal Type Adenocarcinoma from Inverted Papilloma: A Rare Recurrence

    PubMed Central

    Singh, Garima; Singh, Meeta; Chandana, Mansi; Nargotra, Namrata

    2016-01-01

    Inverted Papilloma (IP) is an uncommon and locally aggressive benign tumour of sinonasal region, which tends to recur after surgical resection. Most tumours are confined to the lateral nasal wall and sinuses, with maxillary sinus being most commonly affected and a male preponderance. It has a known association with in situ and invasive carcinomas with a <10% rate of malignant transformation. Most common association has been seen with squamous cell carcinoma and extremely rare association with adenocarcinoma and small cell carcinoma. A 36-year-old male presented with a left sided polypoidal nasal mass and underwent a polypectomy. Pathology results showed IP with mild dysplasia. The polypoidal growth reappeared on the same side after a period of 10 months and on histopathological examination, the growth revealed features of intestinal type adenocarcinoma. IP recurring as adenocarcinoma is rare and even after exhaustive literature search only few cases could be found. Two studies have described recurrence of adenocarcinoma in existing IP previously. We report an unusual case of inverted papilloma showing malignant transformation into an intestinal type adenocarcinoma in a 36-year-old male patient within 10 months of previous surgery. PMID:28050382

  16. Artificial Blood for Dogs

    PubMed Central

    Yamada, Kana; Yokomaku, Kyoko; Kureishi, Moeka; Akiyama, Motofusa; Kihira, Kiyohito; Komatsu, Teruyuki

    2016-01-01

    There is no blood bank for pet animals. Consequently, veterinarians themselves must obtain “blood” for transfusion therapy. Among the blood components, serum albumin and red blood cells (RBCs) are particularly important to save lives. This paper reports the synthesis, structure, and properties of artificial blood for the exclusive use of dogs. First, recombinant canine serum albumin (rCSA) was produced using genetic engineering with Pichia yeast. The proteins showed identical features to those of the native CSA derived from canine plasma. Furthermore, we ascertained the crystal structure of rCSA at 3.2 Å resolution. Pure rCSA can be used widely for numerous clinical and pharmaceutical applications. Second, hemoglobin wrapped covalently with rCSA, hemoglobin–albumin cluster (Hb-rCSA3), was synthesized as an artificial O2-carrier for the RBC substitute. This cluster possesses satisfactorily negative surface net charge (pI = 4.7), which supports enfolding of the Hb core by rCSA shells. The anti-CSA antibody recognized the rCSA exterior quantitatively. The O2-binding affinity was high (P50 = 9 Torr) compared to that of the native Hb. The Hb-rCSA3 cluster is anticipated for use as an alternative material for RBC transfusion, and as an O2 therapeutic reagent that can be exploited in various veterinary medicine situations. PMID:27830776

  17. From Reflux Esophagitis to Esophageal Adenocarcinoma.

    PubMed

    Souza, Rhonda F

    Reflux esophagitis causes Barrett's metaplasia, an abnormal esophageal mucosa predisposed to adenocarcinoma. Medical therapy for reflux esophagitis focuses on decreasing gastric acid production with proton pump inhibitors. We have reported that reflux esophagitis in a rat model develops from a cytokine-mediated inflammatory injury, not from a caustic chemical (acid) injury. In this model, refluxed acid and bile stimulate the release of inflammatory cytokines from esophageal squamous cells, recruiting lymphocytes first to the submucosa and later to the luminal surface. Emerging studies on acute reflux esophagitis in humans support this new concept, suggesting that reflux-induced cytokine release may be a future target for medical therapies. Sometimes, reflux esophagitis heals with Barrett's metaplasia, a process facilitated by reflux-related nitric oxide (NO) production and Sonic Hedgehog (Hh) secretion by squamous cells. We have shown that NO reduces expression of genes that promote a squamous cell phenotype, while Hh signaling induces genes that mediate the development of the columnar cell phenotypes of Barrett's metaplasia. Agents targeting esophageal NO production or Hh signaling conceivably could prevent the development of Barrett's esophagus. Persistent reflux promotes cancer in Barrett's metaplasia. We have reported that acid and bile salts induce DNA damage in Barrett's cells. Bile salts also cause NF-x03BA;B activation in Barrett's cells, enabling them to resist apoptosis in the setting of DNA damage and likely contributing to carcinogenesis. Oral treatment with ursodeoxycholic acid prevents the esophageal DNA damage and NF-x03BA;B activation induced by toxic bile acids. Altering bile acid composition might be another approach to cancer prevention.

  18. Perspectives in the treatment of pancreatic adenocarcinoma

    PubMed Central

    Cid-Arregui, Angel; Juarez, Victoria

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is an incurable lethal disease whose incidence rate is growing. There is no effective screening for detection of early stage tumors and, in most cases, PDAC is diagnosed at advanced disease stages, when radical pancreatic resection is not possible. The aggressive nature of pancreatic tumor cells lies in the complex genetic mechanisms behind their uncontrolled capability to grow and metastasize, which involve essential adaptive changes in cellular metabolism, signaling, adhesion and immunoediting. In addition, PDAC cells promote a dense functional stroma that facilitates tumor resistance to chemotherapy and radiation. During the last two decades, gemcitabine has been the reference for the systemic treatment of PDAC. However, recently, a regimen combining fluorouracil, irinotecan, oxaliplatin, and leucovorin (FOLFIRINOX) and another combining albumin-bound paclitaxel with gemcitabine have shown clear therapeutic advantage in advanced PDAC, with survival outcomes of 11.3 and 8.5 mo on phase III trials, respectively, over single-agent gemcitabine. With the pending issue of their higher toxicities, these regimens set the reference for ongoing and future clinical studies in advanced PDAC. In addition, the efficacy of oral fluoropyrimidine (S-1) has been well documented in Asiatic PDAC patients. The development of therapeutic approaches other than cytotoxic drugs has proven difficult in the past, with only one drug (erlotinib) approved to date. Besides, a number of agents targeting signaling pathways in tumor or stroma cells are being investigated. Likewise, immunotherapies that target PDAC in various ways are the subject of a number of clinical trials. The search for reliable biomarkers with diagnostic and prognostic value using genomics and mass spectrometry methods may facilitate monitoring and refinement of therapies. This review focuses on current understanding of the pathogenesis of PDAC and the latest developments in the

  19. Gemcitabine resistance in pancreatic ductal adenocarcinoma.

    PubMed

    Binenbaum, Yoav; Na'ara, Shorook; Gil, Ziv

    2015-11-01

    Pancreatic ductal adenocarcinoma (PDA) ranks fourth among cancer related deaths. The disappointing 5-year survival rate of below 5% stems from drug resistance to all known therapies, as well as from disease presentation at a late stage when PDA is already metastatic. Gemcitabine has been the cornerstone of PDA treatment in all stages of the disease for the last two decades, but gemcitabine resistance develops within weeks of chemotherapy initiation. From a mechanistic perspective, gemcitabine resistance may result from alterations in drug metabolism until the point that the cytidine analog is incorporated into the DNA, or from mitigation of gemcitabine-induced apoptosis. Both of these drug resistance modalities can be either intrinsic to the cancer cell, or influenced by the cancer microenvironment. Mechanisms of intrinsic gemcitabine resistance are difficult to tackle, as many of the genes that drive the carcinogenic process itself also interfere with gemcitabine-induced apoptosis. In this regard, recent understanding of the involvement of microRNAs in gemcitabine resistance may offer new opportunities to overcome intrinsic gemcitabine resistance. The characteristically fibrotic and immune infiltrated stroma of PDA that accompanies tumor inception and expansion is a lush ground for treatments aimed at targeting tumor microenvironment-mediated drug resistance. In the last couple of years, drugs interfering with tumor microenvironment have matured to clinical trials. Although drugs inducing 'stromal depletion' have yet failed to improve survival, they have greatly increased our understanding of tumor microenvironment-mediated drug resistance. In this review we summarize the current knowledge on intrinsic and environment-mediated gemcitabine resistance, and discuss the impact of these pathways on patient screening, and on future treatments aimed to potentiate gemcitabine activity.

  20. Adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive pulmonary adenocarcinoma--analysis of interobserver agreement, survival, radiographic characteristics, and gross pathology in 296 nodules.

    PubMed

    Boland, Jennifer M; Froemming, Adam T; Wampfler, Jason A; Maldonado, Fabien; Peikert, Tobias; Hyland, Courtney; de Andrade, Mariza; Aubry, Marie Christine; Yang, Ping; Yi, Eunhee S

    2016-05-01

    The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society and 2015 World Health Organization classifications of lung adenocarcinoma recommend designating tumors showing entirely lepidic growth as adenocarcinoma in situ (AIS) and lepidic tumors with invasion less than or equal to 5 mm as minimally invasive adenocarcinoma (MIA), both of which have superior outcome to conventional invasive adenocarcinoma (IA). Data on interobserver variability within this classification are limited, and further validation of the superior survival of AIS and MIA is needed. A total of 296 surgically excised pulmonary adenocarcinomas were reviewed from 254 patients (1997-2009). Slides were independently reviewed by 2 pulmonary pathologists who categorized tumors as AIS, MIA, or IA. Of 296 nodules, 244 (82.4%) were agreed upon by both observers: 10 AIS, 61 MIA, and 173 IA (κ = 0.63, good agreement). In 6 cases (2%), there was disagreement between AIS and MIA; in 45 cases (15%), there was disagreement between MIA and IA; and in 1 case, there was disagreement between AIS and IA. Overall survival was significantly different among categories as determined by both observers. Cases with disagreement between MIA and IA had similar survival to agreed MIA. Disease-specific 10-year survival was 100% for AIS (both observers) and 97.3% and 97.6% for MIA, although this did not reach statistical significance compared to IA for either observer. Good agreement was present between observers when classifying tumors as AIS, MIA, and IA. Significant differences in overall survival were present between the 3 groups for both observers, and interobserver variability was evident. Patients with AIS and MIA experienced excellent DSS.