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Sample records for neu-induced mammary carcinomas

  1. Mammary Analogue Secretory Carcinoma.

    Science.gov (United States)

    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.

  2. Mammary carcinoma diagnostics and therapy; Diagnostik und Therapie des Mammakarzinoms

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    Fischer, Uwe; Baum, Friedemann (eds.) [Diagnostisches Brustzentrum Goettingen BZG, Goettingen(Germany)

    2014-11-01

    The book on mammary carcinoma diagnostics and therapy covers the following issues: development, anatomy and physiology of the mammary glands, pathology of benign and malign mammary gland changes, non-imaging diagnostics; mammography; ultrasonic mammography; magnetic resonance tomography of the mammary glands; imaging diagnostics findings; mammary interventions; examination concepts; operative therapy of the mammary carcinoma; chemotherapy of the mammary carcinoma; radio-oncological therapy of the mammary carcinoma; logistics in a medical center for mammary gland diseases; logistics in an interdisciplinary center for mammary diseases; dialogue conduction and psycho-social attendance.

  3. CD49f and CD61 identify Her2/neu-induced mammary tumor-initiating cells that are potentially derived from luminal progenitors and maintained by the integrin-TGFβ signaling.

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    Lo, P-K; Kanojia, D; Liu, X; Singh, U P; Berger, F G; Wang, Q; Chen, H

    2012-05-24

    Human epidermal growth factor receptor 2 (HER2)/Neu is overexpressed in 20-30% of breast cancers and associated with aggressive phenotypes and poor prognosis. For deciphering the role of HER2/Neu in breast cancer, mouse mammary tumor virus (MMTV)-Her2/neu transgenic mice that develop mammary tumors resembling human HER2-subtype breast cancer have been established. Several recent studies have revealed that HER2/Neu is overexpressed in and regulates self renewal of breast tumor-initiating cells (TICs). However, in the MMTV-Her2/neu transgenic mouse model, the identity of TICs remains elusive, despite previous studies showing supportive evidence for existence of TICs in Her2/neu-induced mammary tumors. Through systematic screening and characterization, we identified that surface markers CD49f, CD61 and ESA were aberrantly overexpressed in Her2-overexpressing mammary tumor cells. Analysis of these markers and CD24 detected anomalous expansion of the luminal progenitor population in preneoplastic mammary glands of Her2/neu transgenic mice, indicating that aberrant luminal progenitors originated in Her2-induced mammary tumors. The combined markers, CD49f and CD61, further delineated the CD49f(high)CD61(high)-sorted fraction as a TIC-enriched population, which displayed increased tumorsphere formation ability, enhanced tumorigenicity both in vitro and in vivo and drug resistance to pacitaxel and doxorubicin. Moreover, the TIC-enriched population manifested increased transforming growth factor-β (TGFβ) signaling and exhibited gene expression signatures of stemness, TGFβ signaling and epithelial-to-mesenchymal transition. Our findings that self-renewal and clonogenicity of TICs were suppressed by pharmacologically inhibiting the TGFβ signaling further indicate that the TGFβ pathway is vital for maintenance of the TIC population. Finally, we showed that the integrin-β3 (CD61) signaling pathway was required for sustaining active TGFβ signaling and self-renewal of TICs

  4. Metastatic mammary carcinoma in a cow

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    Manoela Marchezan Piva

    Full Text Available ABSTRACT: Mammary gland neoplasms in cattle are rarely observed in the field veterinary diagnostics routine. Therefore, the objective of this study is to report a metastatic mammary carcinoma in a fourteen-year-old Holstein cow in the state of Santa Catarina, Brazil. The animal was diagnosed by the field veterinarian with clinical mastitis that was unresponsive to treatment, and was euthanized due to the poor prognosis. At the necropsy, multiple yellow, firm, and sometimes friable nodules, ranging from 0.1 to 20cm were observed in all mammary glands, lymph nodes, kidneys, spleen, liver, pancreas, mediastinal lymph nodes, heart, and lungs. The final diagnosis of mammary carcinoma was established through the association of clinical, necropsy, histopathological, and immunohistochemical findings. Differential diagnoses included diseases such as bovine tuberculosis and chronic fungal or bacterial mastitis.

  5. Mammary Analogue Secretory Carcinoma Mimicking Salivary Adenoma

    OpenAIRE

    Williams, Lindsay; Chiosea, Simion I.

    2013-01-01

    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 g...

  6. Squamous Cell Carcinoma of Mammary Gland in Domestic Cat

    OpenAIRE

    Filgueira,Kilder Dantas; Reche Junior,Archivaldo

    2012-01-01

    Background: In the feline species, 80% to 93% of neoplasias in the mammary gland are malignant, being the majority carcinomas. Among them, there is the mammary squamous cell carcinoma, which amounts to a very rare neoplasm in the domestic cat, with considerable potential for malignancy. This study aimed to report a case of squamous cell mammary carcinoma in the feline species. Case: A female cat, mixed breed, ten years old, presented history of skin lesion. The cat had been spayed two years b...

  7. Tubulopapillary mammary carcinoma in a brown bear (Ursus arctos).

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    Nak, Deniz; Cangul, I Taci; Nak, Yavuz; Cihan, Huseyin; Celimli, Nureddin

    2008-04-01

    A 28-yr-old, nulliparous female brown bear (Ursus arctos) at the Karacabey Ovakurusu Bear Sanctuary presented with an enlargement of the mammary gland. Three other nodules were also noted in the proximity of the mammary gland and over the vulva. Clinical, hematologic, ultrasonographic, and radiologic examinations were performed; the enlarged mammary gland was removed and the other masses were also excised. Histopathologic examination revealed tubulopapillary carcinoma of the mammary gland, and the other masses were diagnosed as epidermoid cysts. This is the first reported case of tubulopapillary mammary carcinoma accompanied by epidermoid cysts in a bear.

  8. Epithelioid mammary myofibroblastoma mimicking invasive lobular carcinoma.

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    Arafah, Maria A; Ginter, Paula S; D'Alfonso, Timothy M; Hoda, Syed A

    2015-06-01

    A case of a 53-year-old woman with the epithelioid variant of mammary myofibroblastoma, which was initially misinterpreted as invasive lobular carcinoma, is presented. A needle core biopsy of the 1.6 cm mass showed interlacing bundles of epithelioid myofibroblasts amid dense fibrous tissue associated with lobular carcinoma in situ of the classical type. Most epithelioid cells showed nuclear atypia, and a few exhibited signet-ring cytology. Immunoreactivity for estrogen and progesterone receptors further compounded the deception, and the neoplasm was misinterpreted as invasive lobular carcinoma. Excisional biopsy showed a circumscribed stromal tumor with foci suspicious for invasive lobular carcinoma. The latter was excluded by cytokeratin negativity throughout the tumor. The overall histopathological appearance and immunostaining pattern was confirmatory of myofibroblastoma. This case report emphasizes the potential for mistaking epithelioid myofibroblastoma for invasive lobular carcinoma--particularly in the setting of limited sampling, hormone-receptor immunoreactivity of the lesional cells, and synchronous lobular carcinoma in situ. © The Author(s) 2015.

  9. Cytopathologic features of mammary analogue secretory carcinoma.

    Science.gov (United States)

    Bishop, Justin A; Yonescu, Raluca; Batista, Denise A S; Westra, William H; Ali, Syed Z

    2013-05-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is defined by ETV6-NTRK3 gene fusion. To the best of the authors' knowledge, only rare case reports of the cytopathologic features of MASC have been published to date. A wide variety of archival salivary gland tumors were tested for ETV6 translocation by break-apart fluorescent in situ hybridization. Positive cases with preoperative fine-needle aspiration (FNA) specimens or intraoperative touch preparations were retrieved from the archives of The Johns Hopkins Hospital. All smears were reviewed and the cytologic characteristics were described. Five cases of MASC with cytopathologic material (4 FNA specimens and 1 touch preparation) were identified. The cases occurred in 3 men and 2 women ranging in age from 21 years to 78 years (mean, 52 years). On the cytologic smears, the MASCs were variably cellular and exhibited 2 different architectural patterns: 1) intact tissue fragments with isomorphic cells arranged in a sheet-like or papillary configuration; and 2) dispersed and dissociated cells with a mostly "histiocyte-like" appearance with large cells containing abundant vacuolated cytoplasm. No matrix tissue or stromal spindled cells were present. The cells did not display acinic differentiation in the form of cytoplasmic zymogen granules. In each case, the preoperative FNA correctly identified a neoplasm, and the most frequent diagnostic considerations were acinic cell carcinoma, mucoepidermoid carcinoma, and pleomorphic adenoma. MASC is a newly described salivary gland tumor that should be considered in the differential diagnosis of low-grade salivary gland neoplasms. Its cytologic features overlap considerably with those of other tumors, especially acinic cell carcinoma and mucoepidermoid carcinoma. Copyright © 2013 American Cancer Society.

  10. Mammary analogue secretory carcinoma mimicking salivary adenoma.

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    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.

  11. [Mammary carcinoma in a patient with hyperprolactinemia].

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    Gola, M; Papi, G; Tavernari, V; Pesenti, M; Ficarra, G; Velardo, A

    1997-12-01

    In 1990, a 50 year-old man was referred to us for hyperprolactinemia. At 37 years of age the patient had undergone left mastectomy, for a histologically confirmed gynecomastia and, in 1989, he had undergone pituitary adenomectomy, for a PRL secreting macroadenoma (PRL = 3520 ng/ml). Persistently high PRL plasma levels (PRL = 550 ng/ml) showed an incomplete surgical removal of the adenoma and as a consequence, radiotherapy of the pituitary area was performed in 1990. When the patient referred to us, PRL plasma levels were still pathologic and medical therapy with bromocriptine was started. A year later a replacement therapy with cortisone, testosterone, L-thyroxine, was commenced, as the patient presented a post-radiotherapy hypopituitarism. Since the treatment with bromocriptine was unsuccessful, the drug was replaced with cabergoline, but not even the latter was able to normalize PRL plasma levels. In 1996, a nodule of 3 cm in diameter was discovered under his right mammary areola. The nodule biopsy showed a grade II infiltrating ductal breast carcinoma positive to the estrogen and progesterone receptors analysis. A right total mastectomy was performed and the diagnosis was confirmed through histological examination. A case of gynecomastia and breast cancer in a male patient who had been exposed to high PRL plasma levels for several years is reported. In this patient, both elevated PRL plasma levels and a relative hyperestrogenic state may have contributed to originate breast cancer.

  12. Large mammary hamartoma with focal invasive ductal carcinoma

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    Pervatikar Suneet

    2009-04-01

    Full Text Available Mammary hamartomas are uncommon benign lesions rarely associated with malignancy. We report a case of a 25-year-old female patient presenting with a lump in the left breast. Fine needle aspiration cytology showed features of invasive ductal carcinoma along with normal benign glands that were mistaken for normal breast tissue. However, the mastectomy specimen revealed the malignant mass within a larger hamartomatous mass. Mammary hamartomas are benign lesions but, on exceedingly rare occasions, they may be involved by incidental, coexisting carcinoma, as illustrated in this case report.

  13. Nasopharyngeal carcinoma metastasis to the mammary gland: A case report.

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    Li, Shuang; Yang, Jiyuan

    2015-01-01

    Nasopharyngeal carcinoma is the second most common type of malignancy in Southern China. Metastatic sites are usually multifocal and involve the bones, lungs and distant lymph nodes. To date, there have been no studies with regard to nasopharyngeal carcinoma metastasis to the mammary gland. In the current study, the case of a 56-year-old female with nasal obstruction, epitaxis and a bilateral neck mass is presented. Following a series of examinations, the patient was diagnosed with nasopharyngeal carcinoma (cT3N3M0). Subsequently, the patient received radical radiation therapy. After three months, a mass was identified in the left breast, together with enlargement of multiple lymph nodes in the left axilla. The patient underwent a mastectomy and pathological examination revealed that the breast mass and axillary lymph node tissues were derived from the nasopharynx. To the best of our knowledge, this is the first report of a nasopharyngeal carcinoma that metastasized to the mammary gland.

  14. Nasopharyngeal carcinoma metastasis to the mammary gland: A case report

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    Li, Shuang; Yang, Jiyuan

    2014-01-01

    Nasopharyngeal carcinoma is the second most common type of malignancy in Southern China. Metastatic sites are usually multifocal and involve the bones, lungs and distant lymph nodes. To date, there have been no studies with regard to nasopharyngeal carcinoma metastasis to the mammary gland. In the current study, the case of a 56-year-old female with nasal obstruction, epitaxis and a bilateral neck mass is presented. Following a series of examinations, the patient was diagnosed with nasopharyn...

  15. Mammary analogue secretory carcinoma: A rare salivary gland tumour

    African Journals Online (AJOL)

    Salivary gland malignancy is rare, with a global annual incidence of. 3 per 100 000 people.[1,2] A rare salivary gland tumour, mammary analogue secretory carcinoma (MASC), has only recently been described.[3] The few reports and studies concerning MASC have been published in several pathology journals. We report ...

  16. Mammary analogue secretory carcinoma: A rare salivary gland tumour

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    B S Jackson

    2017-04-01

    Full Text Available Mammary analogue secretory carcinoma (MASC is a rare and recently described tumour of the salivary glands. MASC has similar histomorphological and immunohistochemical features of secretory carcinoma of the breast. MASC can be mistaken for other salivary gland tumours, especially acinic cell carcinoma. A 28-year-old man was diagnosed with a rare salivary gland tumour in Pretoria, South Africa (SA. To our knowledge, a report of MASC in SA has not previously been published. The surgeons dealing with salivary gland tumours should be aware of the clinical presentation. Current treatment is similar to that of other salivary gland malignancies.

  17. Mammary analogue secretory carcinoma: A rare salivary gland tumour.

    Science.gov (United States)

    Jackson, B S; Pratt, T L; Van Rooyen, A

    2017-03-29

    Mammary analogue secretory carcinoma (MASC) is a rare and recently described tumour of the salivary glands. MASC has similar histomorphological and immunohistochemical features of secretory carcinoma of the breast. MASC can be mistaken for other salivary gland tumours, especially acinic cell carcinoma. A 28-year-old man was diagnosed with a rare salivary gland tumour in Pretoria, South Africa (SA). To our knowledge, a report of MASC in SA has not previously been published. The surgeons dealing with salivary gland tumours should be aware of the clinical presentation. Current treatment is similar to that of other salivary gland malignancies.

  18. [Mammary analog secretory carcinoma of the parotid gland].

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    Guérin, Maxime; Diedhiou, Abdoulaye; Nallet, Emmanuel; Duflo, Suzy; Laé, Marick; Wassef, Michel

    2014-10-01

    Mammary analog secretory carcinoma (MASC) of the parotid gland is a rare and recently described lesion. We report the case of a 46-year-old man with a tumor of the parotid gland which was carried to the diagnosis of MASC. Diagnostic was confirmed by highlighting the ETV6-NTRK3 gene translocation. However, some morphologic and immunohistochemical features are suggestive of this entity. This carcinoma should be distinguished from its main differential diagnoses: acinic cell carcinoma and low grade cribriform cystadenocarcinoma. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  19. STUDY OF OVARIAN CHANGES IN RATS WITH MAMMARY CARCINOMAS

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    Maja Zečević

    2013-03-01

    Full Text Available The aim of this study was to estimate ovarian changes in 7,12 dimethylbenz (α anthracene (DMBA induced rat mammary carcinomas. The study was carried out on female virgin albino Wistar rats (n=35, age=35-37days, body mass 120-140g, divided into control (n=10 and experimental group (n=25. Anesthetised animals of experimental group were inoculated with 2 mg mixture (1 mg of DMBA and 1 mg of cholesterol-buffer into the fifth left mammary gland. The animals were sacrificed 90 days after implantation, and ovaries and mammary glands were investigated. Mammary gland carcinomas (in situ and/or invasive were pathohistologically verified in 19 experimental animals. Histological, histochemical, and immunohistochemical (cytokeratin AE1/AE3 and PCNA studies of ovaries were performed.Besides non-neoplastic changes, such as decrease in ovary’s volume, reduction in the rate of follicular development and numerous corpora lutea formation were found in the vicinity of preneoplastic changes: papillomatous epithelial hyperplasia and inclusion cysts, microglandular formations with dysplasia and seromucinous microcystic formation. Intensive diffuse PCNA expression was present in the epithelium of glandlike structures, follicular and inclusion cysts.These morphological changes confirmed that DMBA is a pluripotent carcinogen capable to induce a wide spectrum of preneoplastic lesions in the ovaries. The present dilemma is whether the changes described are the consequence of the direct effects of DMBA or of hormonal activity of the induced breast carcinomas, or both.

  20. Aberrant E-cadherin staining patterns in invasive mammary carcinoma

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    Brogi Edi

    2005-11-01

    Full Text Available Abstract Background E-cadherin, a cell surface protein involved in cell adhesion, is present in normal breast epithelium, benign breast lesions, and in breast carcinoma. Alterations in the gene CDH1 on chromosome 16q22 are associated with changes in E-cadherin protein expression and function. Inactivation of E-cadherin in lobular carcinomas and certain diffuse gastric carcinomas may play a role in the dispersed, discohesive "single cell" growth patterns seen in these tumors. The molecular "signature" of mammary lobular carcinomas is the loss of E-cadherin protein expression as evidenced by immunohistochemistry, whereas ductal carcinomas are typically E-cadherin positive. Patients and methods We report on E-cadherin immunostaining patterns in five cases of invasive mammary carcinoma Results These were five exceptional instances in which the E-cadherin immunophenotype did not correspond to the apparent histologic classification of the lesion. These cases which are exceedingly rare in our experience are the subject of this report. Conclusion Findings such as those illustrated in this study occur in virtually all biologic phenomena and they do not invalidate the very high degree of correlation between the expression of E-cadherin and the classification of breast carcinomas as ductal or lobular type on the basis of conventional histologic criteria.

  1. Bone Morphogenetic Proteins stimulate mammary fibroblasts to promote mammary carcinoma cell invasion.

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    Philip Owens

    Full Text Available Bone Morphogenetic Proteins (BMPs are secreted cytokines that are part of the Transforming Growth Factor β (TGFβ superfamily. BMPs have been shown to be highly expressed in human breast cancers, and loss of BMP signaling in mammary carcinomas has been shown to accelerate metastases. Interestingly, other work has indicated that stimulation of dermal fibroblasts with BMP can enhance secretion of pro-tumorigenic factors. Furthermore, treatment of carcinoma-associated fibroblasts (CAFs derived from a mouse prostate carcinoma with BMP4 was shown to stimulate angiogenesis. We sought to determine the effect of BMP treatment on mammary fibroblasts. A large number of secreted pro-inflammatory cytokines and matrix-metallo proteases (MMPs were found to be upregulated in response to BMP4 treatment. Fibroblasts that were stimulated with BMP4 were found to enhance mammary carcinoma cell invasion, and these effects were inhibited by a BMP receptor kinase antagonist. Treatment with BMP in turn elevated pro-tumorigenic secreted factors such as IL-6 and MMP-3. These experiments demonstrate that BMP may stimulate tumor progression within the tumor microenvironment.

  2. Invasive ductal carcinoma of the mammary gland in a mare.

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    Hirayama, K; Honda, Y; Sako, T; Okamoto, M; Tsunoda, N; Tagami, M; Taniyama, H

    2003-01-01

    A 21-year-old thoroughbred mare had a 35 x 14 x 10 cm mass involving the mammary gland. Metastases were found in the kidneys, lungs, skeletal muscles, and regional lymph nodes. Histopathologic examination of the tumor revealed a ductal solid carcinoma with extensive intraductal and intralobular involvement and focal infiltration of the adjacent stroma. The intralobular neoplasms were divided into irregularly shaped islands and sheets of polygonal and spindle-shaped epithelial cells by thick or thin fibrous connective tissue bundles. The neoplastic cells had a small or moderate amount of cytoplasm that stained faintly with eosin and round or oval hyperchromatic nuclei. Immunohistochemically, the neoplastic cells were strongly positive for Lu-5, weakly positive for AE1/AE3, vimentin, and glial fibrillary acidic protein, and negative for cytokeratin 8, cytokeratin 14, alpha-smooth muscle actin, calponin, and S100. The neoplasm was diagnosed as an invasive ductal carcinoma of the mammary gland with multiple metastases.

  3. Combined Telomerase Inhibition and Immunotherapy in the Prevention and Treatment of Mammary Carcinomas

    National Research Council Canada - National Science Library

    Gong, Jianlin

    2007-01-01

    .... The mammary carcinomas occur in multiple stages. In addition, the progressive malignant transformation is closely correlated with telomerase activity using telomeric repeat amplification protocol (TRAP...

  4. Mammary analog secretory carcinoma of thyroid: A case report.

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    Rupp, Aaron P; Bocklage, Thèrése J

    2017-01-01

    Mammary analog secretory carcinoma (MASC) is a recently described rare neoplasm that was first reported in the salivary gland with an associated ETV6-NTRK3 fusion. We present a case of MASC involving and presumably arising in the thyroid, which was originally diagnosed as papillary thyroid carcinoma on fine needle aspiration and surgical resection. The later correct diagnosis of MASC was confirmed by immunohistochemistry and molecular studies. The cytopathological features of MASC in the salivary gland are previously described; however, we present the first cytopathological description of MASC arising in the thyroid with the unique feature of prominent nuclear grooves. Differentiating MASC from overlapping features of cytopathologic mimics such as papillary thyroid carcinoma may carry crucial therapeutic implications. Diagn. Cytopathol. 2017;45:45-50. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

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    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.

  6. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands.

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    Chiosea, Simion I; Griffith, Christopher; Assaad, Adel; Seethala, Raja R

    2012-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described tumour with ETV6 translocation. We aimed to characterize the clinical significance of recognizing MASC. Thirty-six patients with MASC (27 identified retrospectively and nine prospectively) are presented. Historically, MASC mimicked other salivary tumours, as follows: 14 of 37 (37.8%) adenocarcinoma, not otherwise specified, 11 of 89 (12.4%) acinic cell carcinomas (AciCC), one of five (20%) mucin-producing signet ring adenocarcinomas, and one of 165 (0.6%) mucoepidermoid carcinomas. Demographically, MASC affected males more commonly (1.4:1). The average age at diagnosis was 45.7 years. Parotid gland was the most common site of involvement (26 of 36, 72.2%), although other head and neck sites, including the base of tongue, were affected. Of 18 patients with neck dissection, lymph node involvement was identified in four patients (four of 18, 22.2%). Survival analysis of MASC cases presented here, combined with those reported previously, revealed a mean disease-free survival for patients with MASC of 92 months [n = 29; 95% confidence interval (CI) 71-115 months], compared with a mean DFS of 121 months for patients with AciCC (n = 38; 95% CI 92-149, P = 0.43). Although perhaps slightly more aggressive, MASC clinical outcome mimics that of AciCC. © 2012 Blackwell Publishing Ltd.

  7. Neovascularization in canine mammary carcinoma – a case report

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    Alexandra Irimie

    2016-11-01

    Full Text Available The frequency of mammary tumors in canines is three times higher than in women. Contrast enhanced ultrasonography (CEUS is a noninvasive clinical method, that uses special contrast agents (CAs, their role being to layout the microvasculature of different lesions. The aim of this particular method, in this case, was to establish if we can evaluate the malignancy of a mass, given the fact that neovascularization is a malignancy marker. The case is represented by a Silky Terrier breed female dog, 5 years old, that was presented initially with an enlarged polycystic mammary gland and a nervous lactation. The female was initially diagnosed with polycystic mastosis. After 2 more months the mass became denser and enlarged. Before the ovariohisterectomy and unilateral mastectomy surgeries have taken place, a B-Mode standard ultrasound, CEUS and a pulmonary X-ray were performed. Our results integrate this case in “fast in” and “slow in” (type 2 curve. The histological diagnosis was established as a simple cystic papillary carcinoma with a malignancy grade 2. The mean value of the MVD was 13.75 which is a low MVD. We cannot determine a correlation between CEUS and a tumor’s malignancy, and so further studies are needed.

  8. Prevention and Treatment of Spontaneous Mammary Carcinoma with Dendritic Tumor Fusion Cell Vaccine

    National Research Council Canada - National Science Library

    Gong, Jianlin

    2002-01-01

    In the present study, the prevention of cancer development by vaccination with fusion cells was evaluated In a genetically engineered murine model which develops spontaneous mammary carcinomas. The mice (MMT...

  9. Mammary analogue secretory carcinoma: update on a new diagnosis of salivary gland malignancy.

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    Sethi, Roshan; Kozin, Elliott; Remenschneider, Aaron; Meier, Josh; VanderLaan, Paul; Faquin, William; Deschler, Daniel; Frankenthaler, Robert

    2014-01-01

    To review the known histopathologic findings and clinical behavior of mammary analogue secretory carcinoma (MASC). PubMed. Literature search using the terms "Mammary analogue secretory carcinoma," "Mammary analog secretory carcinoma," and "MASC" to identify all relevant publications. MASC is an unusual and rare malignant salivary gland tumor first described in 2010. It shares histologic, immunohistochemical, and genetic features with secretory carcinoma of the breast. The clinical behavior of MASC ranges from slowly growing tumors that infrequently recur after surgical resection to aggressive tumors that cause widespread metastasis and death. Many cases of MASC were discovered in archived cases previously classified as acinic cell carcinoma, mucoepidermoid carcinoma, and adenocarcinoma not otherwise specified. MASC is a newly recognized variant of salivary gland malignancy. Further research is needed to better delineate its overall prevalence and to define an appropriate treatment algorithm for this new clinical entity. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Canine Mammary Carcinomas: A Comparative Analysis of Altered Gene Expression

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    Farruk M. Lutful Kabir

    2015-12-01

    /INK4B, in many human and dog cancers including mammary carcinomas, suggested their important conserved genetic order and localization in orthologous chromosomal regions. miRNAs, as powerful post-transcriptional regulators of most of the cancer-associated genes, have not been well evaluated to date in animal cancer models. Comprehensive expression profiles of miRNAs in CMTs have revealed their altered regulation showing a strong correlation with those found in human breast cancers. These genetic correlations between human and dog mammary cancers will greatly advance our understanding of regulatory mechanisms involving many critical cancer-associated genes that promote neoplasia and contribute to the promising development of future therapeutics.

  11. Physical Confirmation and Comparative Genomics of the Rat Mammary carcinoma susceptibility 3 Quantitative Trait Locus

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    Saasha Le

    2017-06-01

    Full Text Available Human breast and rat mammary cancer susceptibility are complex phenotypes where complete sets of risk associated loci remain to be identified for both species. We tested multiple congenic rat strains to physically confirm and positionally map rat Mammary carcinoma susceptibility 3 (Mcs3—a mammary cancer resistance allele previously predicted at Rattus norvegicus chromosome 1 (RNO1. The mammary cancer susceptible Wistar Furth (WF strain was the recipient, and the mammary cancer resistant Copenhagen (Cop strain was the RNO1-segment donor for congenics. Inbred WF females averaged 6.3 carcinogen-induced mammary carcinomas per rat. Two WF.Cop congenic strains averaged 2.8 and 3.4 mammary carcinomas per rat, which confirmed Mcs3 as an independently acting allele. Two other WF.Cop congenic strains averaged 6.6 and 8.1 mammary carcinomas per rat, and, thus, did not contain Mcs3. Rat Mcs3 was delimited to 27.8 Mb of RNO1 from rs8149408 to rs105131702 (RNO1:143700228-171517317 of RGSC 6.0/rn6. Human genetic variants with p values for association to breast cancer risk below 10−7 had not been reported for Mcs3 orthologous loci; however, human variants located in Mcs3-orthologous regions with potential association to risk (10−7 < p < 10−3 were listed in some population-based studies. Further, rat Mcs3 contains sequence orthologous to human 11q13/14—a region frequently amplified in female breast cancer. We conclude that Mcs3 is an independently acting mammary carcinoma resistance allele. Human population-based, genome-targeted association studies interrogating Mcs3 orthologous loci may yield novel breast cancer risk associated variants and genes.

  12. A Cytogenetic Footprint for Mammary Carcinomas Induced by PhIP in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Christian, A T

    2001-04-01

    PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine), a mutagen/carcinogen belonging to the class of heterocyclic amines (HCAs) found in cooked meats, is a mammary gland carcinogen in rats and has been implicated in the etiology of certain human cancers including breast cancer. To gain insight into the genomic alterations associated with PhIP-induced mammary gland carcinogenesis, we used comparative genomic hybridization (CGH) to examine chromosomal abnormalities in rat mammary carcinomas induced by PhIP, and for comparison, by DMBA (7,12-dimethylbenz[a]anthracene), a potent experimental mammary carcinogen. There was a consistent and characteristic pattern of chromosome-region loss in PhIP-induced carcinomas that clearly distinguished them from carcinomas induced by DMBA.

  13. An FNA pitfall: Mammary analog secretory carcinoma mistaken for acinic cell carcinoma due to cytoplasmic granules

    Directory of Open Access Journals (Sweden)

    Nouf Hijazi, MD

    2014-12-01

    Full Text Available In the salivary gland, a key differential feature of Mammary analog secretory carcinoma (MASC from acinic cell carcinoma (ACC is the lack of cytoplasmic granules. We report a case of a parotid mass incorrectly diagnosed on fine needle aspirate as acinic cell carcinoma due to many cells with basophilic granules suggesting serous acinar differention. Tumor resection revealed a tumor consistent with low grade adenocarcinoma that had eosinophilic, microvacuolar cytoplasm with distinct basophilic granules staining with PASD and mucicarmine. The diagnosis of MASC was confirmed with stains for GCDF-15, mammoglobin, and S100 and FISH consistent with a t(12;15 translocation. Relying on the absence of cytoplasmic granules as a feature to distinguish ACC from MASC is a diagnostic pitfall.

  14. [Clinicopathologic features of mammary analogue secretory carcinoma of salivary glands].

    Science.gov (United States)

    Zhang, X P; Ni, H; Wang, X; Chen, H; Shi, S S; Yu, B; Zhou, X J; Rao, Q

    2017-01-08

    Objective: To investigate the clinicopathological features of mammary analogue secretory carcinoma (MASC) of salivary glands, and its diagnosis, differential diagnosis, immunohistochemistry and molecular pathology. Methods: Seventeen cases of MASC were enrolled, with 9 cases of salivary acinar cell carcinoma and 18 cases of adenoid cystic carcinoma as control groups from Nanjing General Hospital from 1997 to 2014 were included in this retrospective study, combined with immunohistochemistry and molecular detection of ETV6-NTRK3 gene fusion. All cases were histologically reviewed with immunohistochemical staining (EnVision) for S-100 protein, SOX10, GATA3, CD117 expression in each group. Fluorescence in situ hybridization (FISH) was used to detect the ETV6-NTRK3 gene fusion. Results: The age of MASC patients ranged from 27 to 74 years with mean age of 47 and ratio of male and female was 4∶3. All cases showed infiltrative growth and diverse cytology and histology, including lobular (8 cases), cystic papillary (3 cases), cribriform mixed with papillary and glandular structures (6 cases) at various proportions. Some tumors of MASC also exhibited solid growth areas with occasional microcystic honeycombed pattern composed of small cysts merged into larger cysts resembling thyroid follicles. S-100 protein and SOX10 were strongly positive in all MASC cases (17/17). In addition, there was insignificant positivity for GATA3 (3/17) and CD117 (4/17). ETV6 gene fusion detection was informative in 12 MASC cases by FISH with 10 positive cases and 2 negative cases. Conclusions: Combined immunohistochemical positivity of S-100 protein, CD117 and SOX10 are useful in the diagnosis and differential diagnosis of MASC. FISH detection of ETV6-NTRK3 fusion offers an additional molecular diagnostic marker for the diagnosis.

  15. Mammary Analogue Secretory Carcinoma (MASC of the salivary gland: A new tumor entity

    Directory of Open Access Journals (Sweden)

    Ivan Damjanov

    2016-08-01

    Full Text Available Mammary analogue secretory carcinoma (MASC is a recently described low-grade malignant tumor of the salivary glands, biologically and morphologically equivalent to secretory breast carcinoma. We give a brief overview of this new entity, including morphological, immunohistochemical, molecular-genetic, clinical, epidemiologic features, differential diagnosis, and outcome results.

  16. Mammary Analogue Secretory Carcinoma (MASC) of the salivary gland: A new tumor entity.

    Science.gov (United States)

    Damjanov, Ivan; Skenderi, Faruk; Vranic, Semir

    2016-08-02

    Mammary analogue secretory carcinoma (MASC) is a recently described low-grade malignant tumor of the salivary glands, biologically and morphologically equivalent to secretory breast carcinoma. We give a brief overview of this new entity, including morphological, immunohistochemical, molecular-genetic, clinical, epidemiologic features, differential diagnosis, and outcome results.

  17. Large lipid-rich mammary analogue secretory carcinoma of parotid gland: An unusual case.

    Science.gov (United States)

    Joshi, Prashant; Mridha, Asit Ranjan; Singh, Shuchita; Kinra, Prateek; Ray, Ruma; Thakar, Alok

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) of the salivary gland is a malignant tumor which bears morphologic, immunohistochemical and molecular features similar to those of mammary secretory carcinoma. The tumor is considered as a low-grade malignancy perhaps slightly more aggressive than acinic cell carcinoma. High-grade transformation with recurrences, regional nodal involvement, metastases, and cancer-related death has been reported in a few cases. We report an unusual case of large MASC of the parotid gland in a young patient without regional lymph node involvement. To the best of our knowledge till date such a large MASC of the salivary gland has not been reported in the English literature.

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

    Science.gov (United States)

    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. © 2013.

  19. Secondary Inflammatory Mammary Carcinoma in a Cat? Clinical and Cytological Findings

    Directory of Open Access Journals (Sweden)

    Tuğba Seval Fatma TOYDEMİR

    2015-01-01

    Full Text Available A case of secondary feline mammary tumor described and discussed with its clinical features similar to inflammatory mammary carcinoma (IMC in this paper. In cats, there were only very few cases of IMC reported until now. A 14-year-old, longhaired female cat was presented to the clinic for the rapid onset of erythema, local pain and warmth of the inguinal region, with a mild exudative haemorrhagic-ulcereted lesion in association with a good-defined underlying mass. The cat had bilateral mastectomy surgery four years ago. Cytological findings were highly associated with inflammatory mammary carcinoma. Due to diffuse pulmonary metastases of the cat surgery could not be suggested as a treatment. In conclusion 1 feline IMC could be useful as an animal model of human inflammatory breast cancer 2 mammary cancer patients should be approached cautiously after even bilaterally performed mastectomy surgeries.

  20. Calcarea carbonica derivative complex (M8) as adjuvant treatment of inflammatory mammary carcinoma in a dog

    OpenAIRE

    Simone Domit Guérios; Carolina Camargo de Oliveira; Daniella Matos da Silva; Eneida Janiscki Da Lozzo; Dorly de Freitas Buchi

    2011-01-01

    Background: Inflammatory mammary carcinoma (IMC) is locally aggressive, fast growing, highly malignant tumor that affects humans and dogs. Affected dogs usually are presented with generalized edema, pain, erythema, and skin ulceration in mammary glands. Surgery is not recommended and an effective treatment has not been established [1]. Calcarea carbonica derivative complex (M8) has demonstrated anticancer properties in a murine model, by improving innate immune response against tumor cells [2...

  1. Thalidomide promotes leukocytosis in mice inoculated with 4T1 mammary carcinoma

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    Diego Carlos dos Reis

    2014-02-01

    Full Text Available The aim of this study was to evaluate the therapy effect of thalidomide in the 4T1 murine mammary carcinoma. 4T1 cell suspension was injected into the posterior left flank of all animals to obtain solid tumors. Five days after inoculation, the treatment group was orally administered 150 mg/kg of thalidomide for seven days. Tumors were measured every 48 hours until the end of treatment. Whole blood was collected for hematology analysis. Our results suggest that thalidomide therapy increase the number of circulating leukocytes in the 4T1 murine mammary carcinoma, and this response is accompanied by a decrease in tumor growth.

  2. Mammary carcinoma in a tiger (Panthera tigris): morphological and immunohistochemical study.

    Science.gov (United States)

    Finotello, Riccardo; Ressel, Lorenzo; Verin, Ranieri; Di Lollo, Simonetta; Baroni, Gianna; Piccinini, Renato; Poli, Alessandro

    2011-03-01

    The histologic and immunohistochemical features of a case of mammary gland carcinoma are described in a 14-yr-old female tiger (Panthera tigris). Immunoreactivity to estrogen receptor (ER), progesterone receptor (PR), tumoral protein 53 (p53), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER-2), and cyclooxigenase-2 (COX-2) was investigated. Neoplastic cells were negative for ER, PR, and p53 but showed positivity for VEGF, HER-2, and COX-2, both in the primary and the metastatic lesions. Histopathologic findings and immunohistochemistry results suggested that the malignant behavior of the reported case could be comparable with some aggressive cat mammary carcinomas.

  3. Significant Growth Inhibition of Canine Mammary Carcinoma Xenografts following Treatment with Oncolytic Vaccinia Virus GLV-1h68

    Science.gov (United States)

    Gentschev, Ivaylo; Ehrig, Klaas; Donat, Ulrike; Hess, Michael; Rudolph, Stephan; Chen, Nanhai; Yu, Yong A.; Zhang, Qian; Bullerdiek, Jörn; Nolte, Ingo; Stritzker, Jochen; Szalay, Aladar A.

    2010-01-01

    Canine mammary carcinoma is a highly metastatic tumor that is poorly responsive to available treatment. Therefore, there is an urgent need to identify novel agents for therapy of this disease. Recently, we reported that the oncolytic vaccinia virus GLV-1h68 could be a useful tool for therapy of canine mammary adenoma in vivo. In this study we analyzed the therapeutic effect of GLV-1h68 against canine mammary carcinoma. Cell culture data demonstrated that GLV-1h68 efficiently infected and destroyed cells of the mammary carcinoma cell line MTH52c. Furthermore, after systemic administration, this attenuated vaccinia virus strain primarily replicated in canine tumor xenografts in nude mice. Finally, infection with GLV-1h68 led to strong inflammatory and oncolytic effects resulting in significant growth inhibition of the tumors. In summary, the data showed that the GLV-1h68 virus strain has promising potential for effective treatment of canine mammary carcinoma. PMID:20631910

  4. Collision of Ductal Carcinoma In Situ of Anogenital Mammary-like Glands and Vulvar Sarcomatoid Squamous Cell Carcinoma.

    Science.gov (United States)

    Tran, Tien A N; Deavers, Michael T; Carlson, J Andrew; Malpica, Anais

    2015-09-01

    A spectrum of invasive adenocarcinomas presumably arising from the anogenital mammary-like glands of the vulva has been reported. Even rarer are the cases of pure ductal carcinoma in situ that originated from these unique glandular structures. Herein, we report an 81-yr-old woman presented with an invasive well-differentiated squamous cell carcinoma of the vulva. Unexpectedly, the underlying dermis demonstrated a cystically dilated structure that displayed a layer of malignant squamous cells in the periphery, and a second centrally located population of neoplastic cells exhibiting glandular differentiation. In addition, a spindle and pleomorphic malignant cell population consistent with a sarcomatoid carcinoma was identified around the cystic structure. Scattered benign anogenital mammary-like glands were present in the adjacent dermis. The histologic and immunohistochemical findings were consistent with those of vulvar squamous cell carcinoma that has undergone sarcomatoid transformation after spreading in a pagetoid fashion into an underlying focus of ductal carcinoma in situ of anogenital mammary-like gland origin.

  5. Salinomycin inhibits canine mammary carcinoma in vitro by targeting cancer stem cells.

    Science.gov (United States)

    Du, Hongchao; Zhou, Bin; Zhang, Hong; Jin, Yipeng; Zhang, Di; Lin, Degui

    2017-07-01

    Salinomycin (SAL), a polyether ionophore antibiotic, has been demonstrated to selectively kill cancer stem cells (CSCs) in various types of human tumor. The aim of the present study was to investigate the effects of SAL on canine mammary CSCs. CSCs in canine mammary carcinoma cell lines (CMT7364 and CIPp) were identified using a sphere formation assay and flow cytometry. The chemoresistance, invasive potential and expression of stem cell-associated proteins of these spheres was then analyzed. This demonstrated that the spheres exhibited characteristics of CSCs, including a cluster of differentiation (CD)44+/CD24-/low phenotype, upregulation of Wnt/β-catenin signaling pathway-associated proteins and chemoresistance. The viability of the spheres was decreased in a concentration- and time-dependent manner following treatment with SAL, and the spheres did not exhibit increased resistance to SAL compared with their parental cells. In addition, exposure to SAL inhibited sphere-formation and invasive potential in canine mammary CSCs in a dose-dependent manner. Furthermore, SAL decreased the CD44+/CD24-/low population and downregulated the expression of Wnt/β-catenin signaling-associated proteins (β-catenin, Cyclin D1 and octamer-binding transcription factor 4) in the spheres. In conclusion, the present study demonstrated that SAL is an effective inhibitor of canine mammary CSCs in vitro, indicating that SAL is a promising chemotherapeutic agent for the treatment of canine mammary carcinoma.

  6. Large lipid-rich mammary analogue secretory carcinoma of parotid gland: An unusual case

    Directory of Open Access Journals (Sweden)

    Prashant Joshi

    2015-01-01

    Full Text Available Mammary analogue secretory carcinoma (MASC of the salivary gland is a malignant tumor which bears morphologic, immunohistochemical and molecular features similar to those of mammary secretory carcinoma. The tumor is considered as a low-grade malignancy perhaps slightly more aggressive than acinic cell carcinoma. High-grade transformation with recurrences, regional nodal involvement, metastases, and cancer-related death has been reported in a few cases. We report an unusual case of large MASC of the parotid gland in a young patient without regional lymph node involvement. To the best of our knowledge till date such a large MASC of the salivary gland has not been reported in the English literature.

  7. Cytopathological features of mammary analogue secretory carcinoma--review of literature.

    Science.gov (United States)

    Takeda, Maiko; Kasai, Takahiko; Morita, Kohei; Takeuchi, Mao; Nishikawa, Takeshi; Yamashita, Akinori; Mikami, Shinji; Hosoi, Hiroshi; Ohbayashi, Chiho

    2015-02-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that morphologically resembles mammary secretory carcinoma and carries the identical ETV6-NTRK3 fusion gene. We report a surgical resected case of MASC in the parotid gland of a 41-year-old man. The cytological smears of a preoperative fine-needle aspiration showed many sheets and crowded clusters of monotonous epithelioid cells with mild atypia, suggestive of monomorphic tumor. Histologically, the tumor was composed of cuboidal cells with follicular, tubular, and solid structures, reminiscent of acinic cell carcinoma of follicular variant, which had been previously classified. This case had ETV6-NTRK3 fusion gene transcript confirmed by fluorescence in situ hybridization and reverse transcription polymerase chain reaction. In the cytological and histopathological diagnosis of monomorphic tumor of salivary gland, MASC needs to be taken into consideration as a differential diagnosis. Further immunohistochemical and gene analyses are needed in diagnosis of MASC. © 2014 Wiley Periodicals, Inc.

  8. Cytologic findings of mammary analogue secretory carcinoma arising in the thyroid.

    Science.gov (United States)

    Rodríguez-Urrego, Paula A; Dogan, Snjezana; Lin, Oscar

    2017-06-01

    Mammary analogue secretory carcinoma (MASC) of the salivary gland, first described by Skálová et al in 2010, is a tumor that morphologically and genetically resembles breast secretory carcinoma harboring ETV6-NTRK3 fusion gene. To date, only seven cases of primary thyroid MASC have been described. The overall findings are similar to those seen in the salivary gland counterpart including the ETV6-NTRK3 fusion gene. This is the second report describing the cytologic features of MASC at this primary location, which also showed a classical type papillary carcinoma component. Diagn. Cytopathol. 2017;45:552-556. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Development and characterization of MCF7 mammary carcinoma ...

    African Journals Online (AJOL)

    Purpose: To investigate the development of mammary tumours in female Sprague-dawley rats through a simple subcutaneous injection of human adenocarcinoma breast cells (MCF7) in combination with basement membrane matrix (BME). Methods: Nine Sprague-Dawley rats were divided into three groups. Group A ...

  10. Antiproliferative and apoptotic effect of Pleurotus ostreatus on human mammary carcinoma cell line (michigan cancer foundation-7

    Directory of Open Access Journals (Sweden)

    Krishnamoorthy Deepalakshmi

    2016-01-01

    Conclusion: The study demonstrates a potent anticancer property of P. ostreatus against human mammary carcinoma cells which might be of value in nutraceutical industry. Further investigations are essential to establish it as a treatment against breast cancer.

  11. Establishment and characterization of a new human oestradiol- and progesterone-receptor-positive mammary carcinoma serially transplantable in nude mice.

    Science.gov (United States)

    Naundorf, H; Fichtner, I; Büttner, B; Frege, J

    1992-01-01

    A human mammary carcinoma originating from a postmenopausal patient was successfully transplanted into nude mice. According to the adopted criteria the tumour proved to be oestradiol- and progesterone-receptor-positive. Histological studies of the patient tumour revealed a ductal invasive mammary carcinoma with 80% tubular growth pattern. Following transplantation the adenoid structures decreased to 30%; the mitosis rate and grade of malignancy increased. Treatment of the nude mice with 20 micrograms oestradiol benzoate/mouse caused a loss of the oestradiol receptor of the mammary carcinoma. The mammary carcinoma 3366 can be used for testing of antineoplastic substances, antihormones and for studies in regard to down-regulation or blocking of hormone receptors and possible consequences for therapies.

  12. AHNAK enables mammary carcinoma cells to produce extracellular vesicles that increase neighboring fibroblast cell motility.

    Science.gov (United States)

    Silva, Thaiomara A; Smuczek, Basílio; Valadão, Iuri C; Dzik, Luciana M; Iglesia, Rebeca P; Cruz, Mário C; Zelanis, André; de Siqueira, Adriane S; Serrano, Solange M T; Goldberg, Gary S; Jaeger, Ruy G; Freitas, Vanessa M

    2016-08-02

    Extracellular vesicles play important roles in tumor development. Many components of these structures, including microvesicles and exosomes, have been defined. However, mechanisms by which extracellular vesicles affect tumor progression are not fully understood. Here, we investigated vesicular communication between mammary carcinoma cells and neighboring nontransformed mammary fibroblasts. Nonbiased proteomic analysis found that over 1% of the entire proteome is represented in these vesicles, with the neuroblast differentiation associated protein AHNAK and annexin A2 being the most abundant. In particular, AHNAK was found to be the most prominent component of these vesicles based on peptide number, and appeared necessary for their formation. In addition, we report here that carcinoma cells produce vesicles that promote the migration of recipient fibroblasts. These data suggest that AHNAK enables mammary carcinoma cells to produce and release extracellular vesicles that cause disruption of the stroma by surrounding fibroblasts. This paradigm reveals fundamental mechanisms by which vesicular communication between carcinoma cells and stromal cells can promote cancer progression in the tumor microenvironment.

  13. Surgery and electrochemotherapy treatment of incompletely excised mammary carcinoma in two male pet rats (Rattus norvegicus).

    Science.gov (United States)

    Lanza, Andrea; Pettorali, Michela; Baldi, Alfonso; Spugnini, Enrico P

    2017-03-23

    Two male rats (Rattus norvegicus; 18 and 24 months old), were referred for treatment of large masses located in the axillary area. Following total body radiography and hematological and serum biochemical analysis, the rats were anesthetized, and the masses were surgically removed. Both lesions were diagnosed as mammary carcinoma based on histopathological diagnosis. The tumor beds were treated with two sessions of electrochemotherapy (ECT), two weeks apart. ECT involved cisplatin administration in the tumor bed, followed by a series of eight biphasic electric pulses. The treatment was well tolerated, and the rats were disease-free after 10 and 14 months. Therefore, adjuvant ECT resulted in good local control of mammary carcinoma and can potentially be used for adjuvant treatment of pet rats with cutaneous and adnexal tumors.

  14. Meloxicam decreases the migration and invasion of CF41.Mg canine mammary carcinoma cells.

    Science.gov (United States)

    Iturriaga, María P; Paredes, Rodolfo; Arias, Jose I; Torres, Cristian G

    2017-08-01

    Cyclooxygenase (COX)-2 expression is positively correlated with malignant features in canine mammary carcinomas. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX activity and may therefore possess anticancer effects. Meloxicam is an NSAID that is widely used in human and veterinary medicine. High concentrations of meloxicam have been reported to be antitumorigenic in vitro; however, the effect of meloxicam at concentrations that are equivalent to those that can be obtained in vivo remains unknown. In the current study, the in vitro effects of low-dose meloxicam (0.25 µg/ml) on CF41.Mg canine mammary carcinoma cells were evaluated. The effects on cell proliferation, apoptosis, cell migration and invasion, in addition to the expression of different molecules associated with tumor invasiveness were analyzed. No effect on cell viability and apoptosis were observed. However, cell migration and invasion were significantly reduced following treatment with meloxicam. MMP-2 expression and activity were similarly reduced, explaining the impaired cell invasion. In addition, β-catenin expression was downregulated, while its phosphorylation increased. These results indicate that 0.25 µg/ml meloxicam reduces cell migration and invasion, in part through modulating MMP-2 and β-catenin expression. Additional studies are required to elucidate the mechanism associated with the anti-invasive effect of meloxicam on CF41.Mg cells. The results of the present study suggest that meloxicam has a potential adjunctive therapeutic application, which could be useful in controlling the invasion and metastasis of canine mammary carcinomas.

  15. A pediatric case of mammary analogue secretory carcinoma within the parotid.

    Science.gov (United States)

    Quattlebaum, S Craig; Roby, Brianne; Dishop, Megan K; Said, M Sherif; Chan, Kenny

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) is a recently described entity in the differential diagnosis of salivary gland tumors. It is notable for a characteristic t(12;15)(p13;q25) translocation that results in a unique fusion protein, ETV6-NTRK3. While several studies have retrospectively identified this translocation in cases previously diagnosed as a different salivary malignancy, there have been relatively few cases where this translocation was identified on initial pathology results, and fewer still in a pediatric population. We present a case of a 15 year old female with a slowly enlarging, painless, left facial mass. MRI demonstrated a cystic mass extending into the deep lobe of the parotid, and she underwent parotidectomy. The tumor cells stained positive for S100 and CK19. ETV6 translocation was present, confirming the diagnosis. Mammary analogue secretory carcinoma is a recently described tumor of the salivary glands, which often masquerades as more common primary salivary gland tumors and cysts. More research is needed to characterize the typical behavior of this neoplasm and the optimal treatment regimen. With identification of its characteristic translocation, mammary analogue secretory carcinoma can be easily differentiated from its more prevalent counterparts, and should therefore remain within the differential of the pathologist and head and neck surgeon. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. ETV6 rearrangement in a case of mammary analogue secretory carcinoma of the skin.

    Science.gov (United States)

    Chang, Michael D; Arthur, Allison K; García, Joaquín J; Sukov, William R; Shon, Wonwoo

    2016-11-01

    Mammary analog secretory carcinoma of salivary glands is a relatively recently recognized entity that harbors the ETV6-NTRK3 fusion transcript. To date, only rare cases of mammary analog secretory carcinoma of the skin have been reported. A 57-year-old man presented with a 6.0 cm cystic mass in the axilla, involving the dermis and superficial subcutis. Microscopically, the tumor exhibited nodular aggregation of tubular and microcystic structures embedded in the dense fibrotic and hyalinized stroma. Characteristic 'colloid-like' eosinophilic secretory material was present within intraluminal spaces. Tumor cells were largely characterized by vesicular nuclei with inconspicuous nucleoli and pink vacuolated cytoplasm. With respect to immunohistochemistry, tumor cells were intensely positive for AE1/AE3, Cam 5.2, and CK7, whereas Ber-EP4 and CEA were completely negative. A dual color break-apart fluorescence in situ hybridization probe identified rearrangement of the ETV6 gene locus on chromosome 12. The patient is alive with no evidence of recurrent disease or metastasis 3 years after the initial surgery. In conclusion, we report a rare example of mammary analog secretory carcinoma of the skin with ETV6 rearrangement. Awareness of this unique cutaneous tumor and subsequent reporting of additional cases is necessary for better characterization of its completely clinicopathologic spectrum. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Mammary analogue secretory carcinoma of the salivary glands: a diagnostic dilemma.

    Science.gov (United States)

    Hindocha, N; Wilson, M H; Pring, M; Hughes, C W; Thomas, S J

    2017-04-01

    Mammary analogue secretory carcinoma (MASC) is a recently identified salivary gland neoplasm that can mimic other salivary gland tumours such as acinic cell carcinoma and cystadenocarcinoma. It is distinguished from these by differences in immunohistochemical profile and the identification of an ETV6-NTRK3 translocation (12;15)(p13;q25), which is also found in secretory carcinomas of the breast. Previous publications have suggested that MASC tumours have similar biological behaviour to acinic cell carcinoma. We report two cases of MASC that affected the upper lip, and showed an infiltrative and locally aggressive growth pattern that required several operations to ensure clearance of microscopic tumour cells. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. Identification of prognostic collagen signatures and potential therapeutic stromal targets in canine mammary gland carcinoma.

    Directory of Open Access Journals (Sweden)

    Ashley Case

    Full Text Available Increasing evidence indicates that the tumor microenvironment plays a critical role in regulating the biologic behavior of breast cancer. In veterinary oncology, there is a need for improved prognostic markers to accurately identify dogs at risk for local and distant (metastatic recurrence of mammary gland carcinoma and therefore would benefit from adjuvant therapy. Collagen density and fiber organization have been shown to regulate tumor progression in both mouse and human mammary tumors, with certain collagen signatures predicting poor outcomes in women with breast cancer. We hypothesized that collagen signatures in canine mammary tumor biopsies can serve as prognostic biomarkers and potential targets for treatment. We used second harmonic generation imaging to evaluate fibrillar collagen density, the presence of a tumor-stromal boundary, tumor associated collagen signatures (TACS and individual collagen fiber characteristics (width, length and straightness in grade I/II and grade III canine mammary tumors. Collagen density, as well as fiber width, length and straightness, were inversely correlated with patient overall survival time. Notably, grade III cases were less likely to have a tumor-stromal boundary and the lack of a boundary predicted poor outcome. Importantly, a lack of a defined tumor-stromal boundary and an increased collagen fiber width were associated with decreased survival even when tumor grade, patient stage, ovariohysterectomy status at the time of mammary tumor excision, and histologic evidence of lymphovascular invasion were considered in a multivariable model, indicating that these parameters could augment current methods to identify patients at high risk for local or metastatic progression/recurrence. Furthermore, these data, which identify for the first time, prognostic collagen biomarkers in naturally occurring mammary gland neoplasia in the dog, support the use of the dog as a translational model for tumor

  19. Trefoil Factor-3 (TFF3 Stimulates De Novo Angiogenesis in Mammary Carcinoma both Directly and Indirectly via IL-8/CXCR2.

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    Wai-Hoe Lau

    Full Text Available Mammary carcinoma cells produce pro-angiogenic factors to stimulate angiogenesis and tumor growth. Trefoil factor-3 (TFF3 is an oncogene secreted from mammary carcinoma cells and associated with poor prognosis. Herein, we demonstrate that TFF3 produced in mammary carcinoma cells functions as a promoter of tumor angiogenesis. Forced expression of TFF3 in mammary carcinoma cells promoted proliferation, survival, invasion and in vitro tubule formation of human umbilical vein endothelial cells (HUVEC. MCF7-TFF3 cells with forced expression of TFF3 generated tumors with enhanced microvessel density as compared to tumors formed by vector control cells. Depletion of TFF3 in mammary carcinoma cells by siRNA concordantly decreased the angiogenic behavior of HUVEC. Forced expression of TFF3 in mammary carcinoma cells stimulated IL-8 transcription and subsequently enhanced IL-8 expression in both mammary carcinoma cells and HUVEC. Depletion of IL-8 in mammary carcinoma cells with forced expression of TFF3, or antibody inhibition of IL-8, partially abrogated mammary carcinoma cell TFF3-stimulated HUVEC angiogenic behavior in vitro, as did inhibition of the IL-8 receptor, CXCR2. Depletion of STAT3 by siRNA in MCF-7 cells with forced expression of TFF3 partially diminished the angiogenic capability of TFF3 on stimulation of cellular processes of HUVEC. Exogenous recombinant hTFF3 also directly promoted the angiogenic behavior of HUVEC. Hence, TFF3 is a potent angiogenic factor and functions as a promoter of de novo angiogenesis in mammary carcinoma, which may co-coordinate with the growth promoting and metastatic actions of TFF3 in mammary carcinoma to enhance tumor progression.

  20. Mitigation of DMBA-induced mammary carcinoma in experimental rats by antiangiogenic property of Kalpaamruthaa.

    Science.gov (United States)

    Sathish, Sivaprakasam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2011-06-01

    Extra cellular matrix (ECM) and basement membrane (BM) are important layers that regulate cell structure, cell migration, and cellular proliferation. Degradation of both ECM and BM mediated by proteases favors the tumor invasion and promotes angiogenesis. Female Sprague-Dawley rats weighing 180 ± 10 g were categorized into 6 groups. Group-1 animals served as vehicle control. Group-2 to Group-4 animals were administered with 7,12-dimethylbenz(a)anthracene (25 mg/rat dissolved in olive oil, orally) on day 1 of experimental period to induce mammary carcinoma. (After 90 days, mammary carcinoma was confirmed by histopathological examination). Group-3 and Group-4 rats were subsequently treated with Semecarpus anacardium nut milk extract (SA) and Kalpaamruthaa (KA), respectively. Group-5 and Group-6 animals served as drug control for SA and KA, respectively. Pro-angiogenic factors like proteases, cyclooxygenase-2, and vascular endothelial growth factor were elevated in tumor-bearing animals and decreased in SA- and KA-supplemented rats. Increased levels of these angiogenic factors in tumor-bearing rats indicate the progression of mammary tumor. The decreased levels of these angiogenic in SA- and KA-treated rats may be due to the ameliorative effect of phenolic compounds such as flavonoids, tannins, and other compounds present in the drug.

  1. Mammary Analogue Secretory Carcinoma of Parotid Gland in a Teenage Boy.

    Science.gov (United States)

    Mahmood, Humera; Fatima, Hadia; Faheem, Mohammad

    2017-09-01

    Mammary analogue secretory carcinoma (MASC) is a rare salivary gland malignancy that exhibits resemblance with secretory carcinoma of the breast (SC) due to the presence of ETV6-NTRK3 gene fusion, formerly classified as acinic cell carcinoma. It is a slowly growing painless tumor that exhibits wide range of clinical behavior. This tumor typically affects middle aged people. Less than 100 such cases have been reported in the literature so far with only 8 case reports of patients less than 19 years of age. Very little is known about the clinical management of such cases. We hereby report a case of 15-year boy who had been managed for MASC of left parotid gland with exision.

  2. Role of peptidylarginine deiminase 2 (PAD2) in mammary carcinoma cell migration.

    Science.gov (United States)

    Horibata, Sachi; Rogers, Katherine E; Sadegh, David; Anguish, Lynne J; McElwee, John L; Shah, Pragya; Thompson, Paul R; Coonrod, Scott A

    2017-05-26

    Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process. For our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes in cell migration and cell morphology. We also used these PAD2-modulated cells to test whether PAD2 may be required for EGF-induced cell migration. To determine how PAD2 might promote tumor cell migration in vivo, we tested the effects of PAD2 inhibition on the expression of several cell migration mediators in MCF10DCIS.com xenograft tumors. In addition, we tested the effect of PAD2 inhibition on EGF-induced ductal invasion and elongation in primary mouse mammary organoids. Lastly, using a transgenic mouse model, we investigated the effects of PAD2 overexpression on mammary gland development. Our results indicate that PAD2 depletion or inhibition suppresses cell migration and alters the morphology of MCF10DCIS.com cells. In addition, we found that PAD2 depletion suppresses the expression of the cytoskeletal regulatory proteins RhoA, Rac1, and Cdc42 and also promotes a mesenchymal to epithelial-like transition in tumor cells with an associated increase in the cell adhesion marker, E-cadherin. Our mammary gland organoid study found that inhibition of PAD2 activity suppresses EGF-induced ductal invasion. In vivo, we found that PAD2 overexpression causes hyperbranching in the developing mammary gland. Together, these results suggest that PAD2 plays a critical role in breast cancer cell migration. Our findings that EGF

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Lipid peroxidation in female dogs bearing mammary gland carcinomas

    Directory of Open Access Journals (Sweden)

    I.B. Souza

    Full Text Available RESUMO O estresse oxidativo causa peroxidação lipídica e formação de substâncias reativas ao ácido tiobarbitúrico (TBARS, processo que está comprovadamente associado à progressão de neoplasias malignas em seres humanos. Por sua vez, espécies reativas de oxigênio (EROs são produzidas no processo carcinogênico, de forma que a geração de EROs parece ser, ao mesmo tempo, causa e consequência dele. Em cães, a associação da peroxidação lipídica com a carcinogênese permanece ainda obscura, com estudos escassos, de resultados conflitantes, que, muitas vezes, incluem, dentro de um mesmo grupo amostral, animais portadores de tumores heterogêneos dos pontos de vista morfológico e comportamental, além de estes se apresentarem em estágios bastante distintos. Nesse contexto, buscou-se, na presente investigação, avaliar a concentração plasmática de TBARS em fêmeas hígidas e portadoras de carcinomas mamários com diagnóstico histopatológico de carcinoma mamário tubular simples estágio 4, com comprometimento de linfonodos, porém sem metástases detectadas. Foi observado que as cadelas diagnosticadas com carcinoma mamário tiveram níveis plasmáticos de TBARS significativamente maiores (média de 7,98 ± 1,43μmol/mL, p < 0,0001 em relação às fêmeas consideradas hígidas (média de 6,14 ± 0,53μmol/mL, o que sugere associação entre câncer e maior ocorrência de estresse oxidativo.

  5. Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast

    Directory of Open Access Journals (Sweden)

    Mohamed Mokhtar Desouki

    2015-01-01

    Full Text Available Malignant mesothelioma is an uncommon tumor with strong association with asbestos exposure. Few cases of malignant pleural mesothelioma metastatic to the female breast have been reported. Herein, we presented, for the first time, a case of locally infiltrating malignant pleural mesothelioma forming a mass in the breast of a male as the first pathologically confirmed manifestation of the disease. Breast ultrasound revealed an irregular mass in the right breast which involves the pectoralis muscle. Breast core biopsy revealed a proliferation of neoplastic epithelioid cells mimicking an infiltrating pleomorphic lobular carcinoma. IHC studies showed the cells to be positive for calretinin, CK5/6, WT1, and CK7. The cells were negative for MOC-31, BerEp4, ER, and PR. A final diagnosis of malignant mesothelioma, epithelioid type, was rendered. This case demonstrates the importance of considering a broad differential diagnosis in the setting of atypical presentation with application of a panel of IHC markers.

  6. Ultrasonic appearance of mammary carcinoma with a dedicated whole-breast scanner.

    Science.gov (United States)

    Maturo, V G; Zusmer, N R; Gilson, A J; Bear, B

    1982-03-01

    Forty-four pathologically proved mammary carcinomas were studied by clinical examination, xeroradiography, and ultrasonography with a dedicated whole-breast scanner. Abnormalities reflecting carcinoma were shown by echography in 90% of cases and xeromammography in 97%. Ultrasonic manifestations of malignancy were separated into four categories: (a) a solid, hypoechoic mass; (b) a hyperechoic focus; (c) an irregular, echogenic zone of parenchymal disruption; and (d) an atypical cystic mass. Dedicated ultrasound instruments enhance interpretation and improve differential diagnostic capability. Sonography demonstrates abnormalities better and permits superior definition of abnormal characteristics in a dysplastic breast than in a fatty, atrophic breast, while xeromammography may be more reliable in postmenopausal women with fatty breasts than in women with mammographically dense breasts. One limitation of current ultrasound equipment is the inability to consistently demonstrate microcalcification.

  7. Isolation of stem-like cells from spontaneous feline mammary carcinomas: Phenotypic characterization and tumorigenic potential

    Energy Technology Data Exchange (ETDEWEB)

    Barbieri, Federica; Wurth, Roberto [Section of Pharmacology, Dept. of Internal Medicine Di.M.I., and Center of Excellence for Biomedical Research - University of Genova, Viale Benedetto XV, 2, 16132 Genova (Italy); Ratto, Alessandra; Campanella, Chiara; Vito, Guendalina [Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D' Aosta, National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Piazza Borgo Pila, 16129, Genova (Italy); Thellung, Stefano [Section of Pharmacology, Dept. of Internal Medicine Di.M.I., and Center of Excellence for Biomedical Research - University of Genova, Viale Benedetto XV, 2, 16132 Genova (Italy); Daga, Antonio [Laboratory of Translational Oncology, IRCCS Azienda Ospedaliera Universitaria San Martino - IST- Istituto Nazionale Ricerca sul Cancro, L.go R. Benzi, 10, 16132 Genova Italy (Italy); Cilli, Michele [Animal Facility, IRCCS Azienda Ospedaliera Universitaria San Martino - IST- Istituto Nazionale Ricerca sul Cancro, L.go R. Benzi, 10, 16132 Genova Italy (Italy); Ferrari, Angelo [Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle D' Aosta, National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Piazza Borgo Pila, 16129, Genova (Italy); Florio, Tullio, E-mail: tullio.florio@unige.it [Section of Pharmacology, Dept. of Internal Medicine Di.M.I., and Center of Excellence for Biomedical Research - University of Genova, Viale Benedetto XV, 2, 16132 Genova (Italy)

    2012-04-15

    Current carcinogenesis theory states that only a small subset of tumor cells, the cancer stem cells or tumor initiating cells (TICs), are responsible for tumor formation and progression. Human breast cancer-initiating cells have been identified as CD44-expressing cells, which retain tumorigenic activity and display stem cell-like properties. Spontaneous feline mammary carcinoma (FMC) is an aggressive cancer, which shows biological similarities to the human tumor counterpart. We report the isolation and phenotypic characterization of FMC-derived stem/progenitor cells, showing in vitro self-renewal, long-lasting proliferation and in vivo tumorigenicity. Twenty-one FMC samples were collected, histologically classified and characterized for the expression of Ki67, EGFR, ER-{alpha} and CD44, by immunohistochemistry. By culture in stem cell permissive conditions, we isolated, from 13 FMCs, a CD44-positive subpopulation able to survive and proliferate in vitro as mammospheres of different sizes and morphologies. When injected in NOD/SCID mice, FMC stem-like cells initiate tumors, generating cell heterogeneity and recapitulating the original histotype. In serum-containing medium, spheroid cells showed differentiation properties as shown by morphological changes, the loss of CD44 expression and tumorigenic potential. These data show that stem-defined culture of FMC enriches for TICs and validate the use of these cells as a suitable model for comparative oncology studies of mammary biology and testing therapeutic strategies aimed at eradicating TICs. -- Highlights: Black-Right-Pointing-Pointer Feline mammary carcinoma contain a sub-population of stem-like cells expressing CD44 Black-Right-Pointing-Pointer These grow as spheres in serum-free medium and self-renew Black-Right-Pointing-Pointer Isolated stem-like cancer cells initiate tumor in immunodeficient mice Black-Right-Pointing-Pointer Xenografted tumors are phenotypically similar to the original tumor Black

  8. Effect of Semecarpus anacardium Linn. nut milk extract on glutathione and its associated enzymes in experimentally induced mammary carcinoma.

    Science.gov (United States)

    Mathivadhani, P; Shanthi, P; Sachdanandam, P

    2006-01-01

    Reduced glutathione (GSH) is a ubiquitous thiol-containing tripeptide that plays a key role in the etiology of many diseases and, in particular, cancer. GSH, the foremost internal protective system, participates directly in the destruction of free radical compounds and detoxification of carcinogens. The effect of Semecarpus anacardium nut milk extract was studied for gaining insight into the disease relationship to GSH and its metabolizing enzymes. Mammary carcinoma was induced by giving 7,12-dimethylbenz[a]anthracene (DMBA) (25 mg/mL of olive oil) perorally by gastric intubation, and nut milk extract of S. anacardium was administered orally (200 mg/kg of body weight/day) for 14 days to mammary carcinoma-bearing rats. The levels of GSH and its metabolizing enzyme activities were determined in liver and kidney homogenates. Significant decreases in GSH, glutathione peroxidase, glutathione S-transferase, glutathione reductase, and gamma-glutamylcysteine synthetase and a concomitant increase in oxidized glutathione, gamma-glutamyl transpeptidase, and glucose 6-phosphate dehydrogenase were observed in DMBA-induced mammary carcinoma in rats, while drug treatment reversed the conditions to near normal levels. There was a marked increase in GSH level and gamma-glutamylcysteine synthetase activity in drug control rats. These findings suggest that S. anacardium can exert its protective effect in maintaining the glutathione redox status by restoring the associated enzymes against oxidative stress in experimental mammary carcinoma.

  9. Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse.

    Science.gov (United States)

    Kerjaschki, Dontscho; Bago-Horvath, Zsuzsanna; Rudas, Margaretha; Sexl, Veronika; Schneckenleithner, Christine; Wolbank, Susanne; Bartel, Gregor; Krieger, Sigurd; Kalt, Romana; Hantusch, Brigitte; Keller, Thomas; Nagy-Bojarszky, Katalin; Huttary, Nicole; Raab, Ingrid; Lackner, Karin; Krautgasser, Katharina; Schachner, Helga; Kaserer, Klaus; Rezar, Sandra; Madlener, Sybille; Vonach, Caroline; Davidovits, Agnes; Nosaka, Hitonari; Hämmerle, Monika; Viola, Katharina; Dolznig, Helmut; Schreiber, Martin; Nader, Alexander; Mikulits, Wolfgang; Gnant, Michael; Hirakawa, Satoshi; Detmar, Michael; Alitalo, Kari; Nijman, Sebastian; Offner, Felix; Maier, Thorsten J; Steinhilber, Dieter; Krupitza, Georg

    2011-05-01

    In individuals with mammary carcinoma, the most relevant prognostic predictor of distant organ metastasis and clinical outcome is the status of axillary lymph node metastasis. Metastases form initially in axillary sentinel lymph nodes and progress via connecting lymphatic vessels into postsentinel lymph nodes. However, the mechanisms of consecutive lymph node colonization are unknown. Through the analysis of human mammary carcinomas and their matching axillary lymph nodes, we show here that intrametastatic lymphatic vessels and bulk tumor cell invasion into these vessels highly correlate with formation of postsentinel metastasis. In an in vitro model of tumor bulk invasion, human mammary carcinoma cells caused circular defects in lymphatic endothelial monolayers. These circular defects were highly reminiscent of defects of the lymphovascular walls at sites of tumor invasion in vivo and were primarily generated by the tumor-derived arachidonic acid metabolite 12S-HETE following 15-lipoxygenase-1 (ALOX15) catalysis. Accordingly, pharmacological inhibition and shRNA knockdown of ALOX15 each repressed formation of circular defects in vitro. Importantly, ALOX15 knockdown antagonized formation of lymph node metastasis in xenografted tumors. Furthermore, expression of lipoxygenase in human sentinel lymph node metastases correlated inversely with metastasis-free survival. These results provide evidence that lipoxygenase serves as a mediator of tumor cell invasion into lymphatic vessels and formation of lymph node metastasis in ductal mammary carcinomas.

  10. A systematic review including an additional pediatric case report: Pediatric cases of mammary analogue secretory carcinoma.

    Science.gov (United States)

    Ngouajio, Amanda L; Drejet, Sarah M; Phillips, D Ryan; Summerlin, Don-John; Dahl, John P

    2017-09-01

    Mammary Analogue Secretory Carcinoma (MASC) is a newly characterized salivary gland carcinoma resembling secretory carcinoma of the breast. Prior to being described, MASC was most commonly misdiagnosed as Acinic Cell Carcinoma. Though MASC is predominantly an adult neoplasm, cases have been reported in the pediatric population. Reporting and summarizing of known cases is imperative to understand the prognosis and clinical behavior of MASC. EVIDENCE REVIEW: Web of Science, Medline, EMBASE, and The Cochrane Library were searched for studies that included pediatric cases of MASC. Data on clinical presentation, diagnosis and management, and pathology were collected from all pediatric cases. CONCLUSIONS AND RELEVANCE: Since the first case of MASC in the pediatric population was described in 2011, only 12 cases, including this one, have been described in the literature. With this paucity of information, much remains unknown regarding this new pathologic diagnosis. The collection of clinical outcomes data of children with MASC is needed to better understand the behavior of this malignancy as well as determine optimal treatment regimens. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands.

    Science.gov (United States)

    Mariano, Fernanda Viviane; Gómez, Camila Andrea Concha; de Souza do Nascimento, Juliana; Dos Santos, Harim Tavares; Egal, Erika Said; Montalli, Victor Angelo Martins; Vargas, Pablo Agustin; de Almeida, Oslei Paes; Altemani, Albina

    2016-12-01

    Lysozyme is an enzymatic marker of acinar and intercalated duct cells of normal salivary glands. The aim of this study was to verify whether lysozyme expression could be useful to distinguish acinic cell carcinoma (ACC) from its main mimic, mammary analog secretory carcinoma (MASC). For comparison, DOG1 expression was analyzed as well. Seventeen cases of ACC, 15 MASC, and 125 other salivary tumors were studied. Lysozyme expression was found in tumor cells as well as in secreted material of MASC (86.6 % of cases) and in ductal cells of epithelial-myoepithelial carcinoma (EMC-53.8 %), pleomorphic adenoma (PA-29.1 %) and polymorphous low-grade adenocarcinoma (PLGA-23.8 %). However, in ACC, lysozyme was not expressed. Three patterns of DOG1 staining were seen: apical-luminal, cytoplasmic, and mixed cytoplasmic/membranous. The apical-luminal pattern was detected in ductal cells of ACC (58.8 % of cases), EMC (38.4 %), adenoid-cystic carcinoma (AdCC-35.3 %), PA (8.3 %), and PLGA (4.8 %). These tumors also showed mixed membranous/cytoplasmic staining for DOG1. MASC, mucoepidermoid, and salivary duct carcinomas exhibited only DOG1 cytoplasmic staining. In conclusion, lysozyme cannot be used as a marker of acinar differentiation in salivary tumors. However, lysozyme expression can be helpful to distinguish MASC from ACC due to its high frequency in the former and absence in ACC. It is likely that in MASC, lysozyme expression may reflect a lactational-like secretory differentiation since lysozyme belongs to breast milk proteins. Regarding DOG1 expression, the apical-luminal pattern is related to acinar and intercalated duct differentiation whereas the cytoplasmic staining does not seem to be associated with a specific cellular phenotype.

  13. Inhibitory effect of iron withdrawal by chelation on the growth of human and murine mammary carcinoma and fibrosarcoma cells.

    Science.gov (United States)

    Power Coombs, Melanie R; Grant, Taryn; Greenshields, Anna L; Arsenault, Daniel J; Holbein, Bruce E; Hoskin, David W

    2015-10-01

    Since iron uptake is essential for cell growth, rapidly dividing cancer cells are sensitive to iron depletion. To explore the effect of iron withdrawal on cancer cell growth, mouse and human mammary carcinoma cells (4T1 and MDA-MB-468, respectively) and mouse and human fibrosarcoma cells (L929 and HT1080, respectively) were cultured in the absence or presence of DIBI, a novel iron-chelating polymer containing hydroxypyridinone iron-ligand functionality. Cell growth was measured by a colorimetric assay for cell metabolic activity. DIBI-treated 4T1, MDA-MB-468, L929 and HT1080 cells, as well as their normal counterparts, showed a dose- and time-dependent reduction in growth that was selective for human cancer cells and mouse fibrosarcoma cells. The inhibitory effect of DIBI on fibrosarcoma and mammary carcinoma cell growth was reversed by addition of exogenous iron in the form of iron (III) citrate, confirming the iron selectivity of DIBI and that its inhibitory activity was iron-related. Fibrosarcoma and mammary carcinoma cell growth inhibition by DIBI was associated with S-phase cell cycle arrest and low to moderate levels of cell death by apoptosis. Consistent with apoptosis induction following DIBI-mediated iron withdrawal, fibrosarcoma and mammary carcinoma cells exhibited mitochondrial membrane permeabilization. A comparison of DIBI to other iron chelators showed that DIBI was superior to deferiprone and similar to or better than deferoxamine for inhibition of fibrosarcoma and mammary carcinoma cell growth. These findings suggest that iron withdrawal from the tumor microenvironment with a selective and potent iron chelator such as DIBI may prevent or inhibit tumor progression. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  15. Clinicopathologic and molecular characterization of mammary analogue secretory carcinoma of salivary gland origin.

    Science.gov (United States)

    Baghai, F; Yazdani, F; Etebarian, A; Garajei, A; Skalova, A

    2017-09-01

    Mammary analogue secretory carcinoma (MASC) is a newly recognized salivary gland tumor that harbors a characteristic balanced chromosomal translocation t (12; 15) (p13; q25) resulting in an ETV6-NTRK3 fusion gene. Retrospective study of 111 salivary gland carcinomas revealed 37 cases with secretory features and growth patterns resembling secretory carcinoma of breast. These 37 cases were originally diagnosed as acinic cell carcinoma, adenocarcinoma not otherwise specified and cystadenocarcinoma. Positive immunostaining for S-100 protein and mammaglobin, followed by detection of ETV6 gene rearrangement by FISH and/or ETV6-NTRK3 fusion transcript by RT-PCR were used to identify MASCs. In the cohort of 37 salivary carcinomas with secretory features we have identified 10 cases of MASC. All 10 MASCs were positive for mammaglobin, S-100 protein and SOX10, while staining for DOG1 and p63 protein were mostly absent. In 7/10 cases, both FISH and RT-PCR were positive while three remaining cases showed break of ETV6 gene by FISH analysis and the RT-PCR was negative. Clinical follow-up data were obtained in 6 out of 10 patients with MASC. In 3 patients cervical lymph node metastases developed, one patient with high grade transformed MASC died with multiple distant bone metastases, and local recurrence was observed in three patients. Our clinicopathological data are in keeping with previous studies; in most cases, MASC is a low-grade malignancy with overall favorable prognosis. In rare cases, however, MASC with high-grade transformation may behave aggressively, and these patients could benefit from targeted biological treatment using tyrosine kinase inhibitors. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. The cytopathologic features of mammary analog secretory carcinoma and its mimics.

    Science.gov (United States)

    Samulski, T Danielle; LiVolsi, Virginia A; Baloch, Zubair

    2014-01-01

    Mammary Analogue Secretory Carcinoma (MASC) is a newly recognized neoplasm of the salivary gland, first described in 2010. This tumor harbors a unique translocation, t(12;15)(p13;q25) that results in the fusion of ETV6 with NTRK3 which produces a transformative chimeric tyrosine kinase. To date, few cases of MASC sampled by fine needle aspiration have been reported. Cytologically, MASC can be confused with other oncocytic salivary gland tumors, including Warthin-tumor, acinic cell carcinoma (AciCC) and mucoepidermoid carcinoma. It is characterized by a monomorphic population of lesional cells with round nuclei, prominent nucleoli and abundant, eosinophilic foamy cytoplasm; forming papillary groups with transgressing vessels. Though, based on cytomorphology alone, the definite diagnosis can be challenging, in conjunction with available clinical clues (i.e. male patient, extra-parotid site) MASC should be included in the differential diagnosis of FNA specimens diagnosed as oncocytic salivary gland neoplasms or suspicious for AciCC. Here we present a case of MASC with FNA sampling at our institution.

  17. The cytological features of mammary analogue secretory carcinoma: a series of 6 molecularly confirmed cases.

    Science.gov (United States)

    Griffith, Christopher C; Stelow, Edward B; Saqi, Anjali; Khalbuss, Walid E; Schneider, Frank; Chiosea, Simion I; Seethala, Raja R

    2013-05-01

    Mammary analogue secretory carcinoma (MASC) of the salivary glands is a newly described tumor entity associated with the t(12;15)(p13;q25) ETV6-NTRK3 translocation. Early studies have shown this tumor to be a distinct entity with histologic, biologic, and clinical differences from acinic cell carcinoma and adenocarcinoma, not otherwise specified. Because this tumor was described only recently, it remains relatively unknown outside of head and neck specialty pathology centers. In the current study, 6 cases of fine-needle aspiration cytology from histologically and/or molecularly confirmed cases of MASC are presented. Using cytomorphology, MASC primarily raises the differential diagnosis of an oncocytic salivary gland tumor but there are some features that can suggest the specific diagnosis of MASC. The 6 cases presented in the current study all demonstrated at least focal cytoplasmic vacuolization and papillary formations on smears. MASC can be differentiated from acinic cell carcinoma by a lack of periodic acid-Schiff diastase-positive zymogen granules and S-100 protein positivity. The results of the current study the ability of ETV6 break-apart fluorescence in situ hybridization to detect gene rearrangement on cell block material. This is the first report of a case of MASC prospectively diagnosed on a cytology specimen. Copyright © 2012 American Cancer Society.

  18. The cytopathologic features of mammary analog secretory carcinoma and its mimics

    Directory of Open Access Journals (Sweden)

    T Danielle Samulski

    2014-01-01

    Full Text Available Mammary Analogue Secretory Carcinoma (MASC is a newly recognized neoplasm of the salivary gland, first described in 2010. This tumor harbors a unique translocation, t(12;15(p13;q25 that results in the fusion of ETV6 with NTRK3 which produces a transformative chimeric tyrosine kinase. To date, few cases of MASC sampled by fine needle aspiration have been reported. Cytologically, MASC can be confused with other oncocytic salivary gland tumors, including Warthin-tumor, acinic cell carcinoma (AciCC and mucoepidermoid carcinoma. It is characterized by a monomorphic population of lesional cells with round nuclei, prominent nucleoli and abundant, eosinophilic foamy cytoplasm; forming papillary groups with transgressing vessels. Though, based on cytomorphology alone, the definite diagnosis can be challenging, in conjunction with available clinical clues (i.e. male patient, extra-parotid site MASC should be included in the differential diagnosis of FNA specimens diagnosed as oncocytic salivary gland neoplasms or suspicious for AciCC. Here we present a case of MASC with FNA sampling at our institution.

  19. Mammary analogue secretory carcinoma of salivary glands: diagnostic pitfall with distinct immunohistochemical profile and molecular features.

    Science.gov (United States)

    Bissinger, Oliver; Götz, Carolin; Kolk, Andreas; Bier, Henning A; Agaimy, Abbas; Frenzel, Henning; Perner, Sven; Ribbat-Idel, Julika; Wolff, Klaus Dietrich; Weichert, Wilko; Mogler, Caroline

    2017-10-03

    Mammary analogue secretory carcinoma (MASC) is a newly defined entity among salivary gland malignancies which has just been established in the 4(th) edition of the WHO classification of head and neck tumors. MASC (synonym: secretory carcinoma) are characterized by a specific rearangement of the ETV6 gene locus. Here, we present a series of 3 MASC cases including clinical data with follow-up for up to 26 months. All tumours immunhistochemically displayed strong positivity for cytokeratin 7, and mammaglobin, focal positivity for S100, cytokeratin 5/6 and muc-4. In contrast, immunhistochemical stainings against cytokeratin 14, hormon receptors, Her2/neu, androgen receptor and prostate-specific antigen were consistently negative. FISH analysis showed translocation of the ETV6 gene locus in the majority of tumour cell nuclei. During clinical follow-up, no local relapse or metastasis was detected. As these carcinomas are clinically and radiologically indistinguishable from other salivary gland tumours and as therapeutic approaches and prognosis might differ, we need to be able to diagnose MASC correctly.

  20. CXCR4 expression in feline mammary carcinoma cells: evidence of a proliferative role for the SDF-1/CXCR4 axis

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    Ferrari Angelo

    2012-03-01

    Full Text Available Abstract Background Mammary tumours frequently develop in female domestic cats being highly malignant in a large percentage of cases. Chemokines regulate many physiological and pathological processes including organogenesis, chemotaxis of inflammatory cells, as well as tumour progression and metastasization. In particular, the chemokine/receptor pair SDF-1/CXCR4 has been involved in the regulation of metastatic potential of neoplastic cells, including breast cancer. The aim of this study was the immunohistochemical defininition of the expression profile of CXCR4 in primary and metastatic feline mammary carcinomas and the evaluation of the role of SDF-1 in feline mammary tumour cell proliferation. Results A total of 45 mammary surgical samples, including 33 primary tumours (31 carcinomas and 2 adenomas, 6 metastases, and 4 normal mammary tissues were anlyzed. Tumor samples were collected from a total number of 26 animals, as in some cases concurrent occurrence of neoplasm in more than one mammary gland was observed. Tissues were processed for standard histological examination, and all lesions were classified according to the World Health Organization criteria. CXCR4 expression in neoplastic cells was evaluated by immunohistochemistry. The level of CXCR4 immunoreactivity was semi-quantitatively estimated as CXCR4 score evaluating both the number of positive cells and the intensity of staining. Six primary, fibroblast-free primary cultures were obtained from fresh feline mammary carcinomas and characterized by immunofluorescence for CXCR4 and malignant mammary cell marker expression. SDF-1-dependent in vitro proliferative effects were also assayed. CXCR4 expression was observed in 29 out of 31 malignant tissues with a higher CXCR4 score observed in 4 out of 6 metastatic lesions than in the respective primary tumours. In 2 benign lesions analyzed, only the single basaloid adenoma showed a mild positive immunostaining against CXCR4. Normal tissue did

  1. Influence of autocrine growth hormone on NF-κB activation leading to epithelial-mesenchymal transition of mammary carcinoma.

    Science.gov (United States)

    Baskari, Srinivas; Govatati, Suresh; Madhuri, Vijaya; Nallabelli, Nayudu; K, Paul Marx; Naik, Srinivas; Poornachandar; Balka, Swarna; Tamanam, Raghava Rao; Devi, Venkata Ramana

    2017-10-01

    Progression of breast cancers often depends on hormones among which human growth hormone is prominently involved in breast cancer progression. Earlier studies have reported constitutive activation of nuclear factor-κB, a key regulator of growth hormone receptor-mediated signaling pathway in breast carcinoma, but the precise molecular mechanisms are still elusive. In this study, we investigated the effect of human growth hormone on nuclear factor-κB activation and epithelial-mesenchymal transition in breast carcinoma. Our results explored that autocrine production of human growth hormone enhances cellular proliferation by the activation of nuclear factor-κB (65 kDa) and downregulation of E-cadherin expression. Furthermore, enhanced nuclear factor-κB expression significantly increases cell proliferation and diminishes apoptosis in MCF-7 cell line. Increased expression of nuclear factor-κB significantly enhances mammary carcinoma cell migration and invasion stimulated by autocrine human growth hormone, which results in epithelial-mesenchymal transition of MCF-7 cells. In conclusion, our study revealed the influence of human growth hormone on nuclear factor-κB activity and epithelial-mesenchymal transition in mammary carcinoma. Our findings will help to understand molecular role of "growth hormone-nuclear factor-κB axis" in mammary carcinogenesis which may facilitate the discovery of suitable pathway inhibitors for disease treatment.

  2. A Metastatic Lipid-Rich Carcinoma of the Mammary Gland in a Female Cat: Clinicopathological, Histopathological and Immunohistochemical Features

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    Adrian Florin GAL

    2017-11-01

    Full Text Available Lipid-rich invasive human breast cancer is a rare enigmatic entity among special types of infiltrating duct carcinoma. Our paper reports a lipid-rich mammary carcinoma in a female cat with the gross, microscopic and immunohistochemical description of the tumor. A 13-year-old intact adult female, mixed-breed cat was presented by the owner to the Laboratory of Pathologic Anatomy from the Faculty of Veterinary Medicine Cluj-Napoca, Romania. A complete necropsy examination was performed in our laboratory. The tissue samples were collected and processed by paraffin technique for further histological, histochemical, immunofluorescence and immunohistochemical examination. During the necropsy examination, a subcutaneous mass was discovered on the chest. Several variably sized, well-demarcated neoplasms were noted in the right axillary lymph node, right thoracic wall, pleura, lungs, liver, spleen and kidney. Histologically, the cells frequently formed tubuloacinar structures. The morphology of the described tumor showed features of a poorly differentiated mammary carcinoma. Numerous tumoral cells were large and polygonal, with abundant cytoplasm that showed foam-like cytoplasm. The tumoral cells contained either multiple small or large and solitary vacuoles that pushed the nucleus to the periphery of the cell. Intracytoplasmic vacuoles of the neoplastic cells were positive for Oil-Red-O and negatively with Periodic Acid–Schiff. As for immunofluorescence/immunohistochemistry, nonvacuolated and vacuolated neoplastic cells were positive for cytokeratin and negative for vimentin. Histochemical and immunohistochemical analysis support a diagnosis of lipid-rich mammary carcinoma. This is the second reliable record of a lipid-rich mammary carcinoma in female cat and the first one with internal metastases.

  3. MAMMARY SOLID CARCINOMA WITH SPINAL CORD METASTASIS CARCINOMA SÓLIDO DE GLÂNDULA MAMÁRIA COM METÁSTASE EM MEDULA ESPINHAL

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    Denise Caroline Toledo

    2009-12-01

    Full Text Available

    Mammary neoplasias are common in canine females and carcinomas, among malignant types, occur frequently, especially solid form. At gross view, it can be small and incipient, but it’s invasive and show little differentiation, being able to produce metastasis that can compromise animal survive. This describes a bitch, Fila Brasileiro, six year old with tetraplegy and cervical spinal cord metastasis of mammary solid carcinoma.

    KEYWORDS: Central nervous system, dog, mammary neoplasia.

    Neoplasias mamárias são comuns entre as fêmeas caninas e os carcinomas, dentre as formas malignas, ocorrem com maior frequência, particularmente o tipo sólido. Estes podem apresentar-se pequenos e incipientes à macroscopia, contudo são invasivos e pouco diferenciados, com possibilidade de produzir metástases que comprometem a sobrevida do animal. Assim, descreve-se o caso de uma cadela, da raça Fila Brasileiro, de seis anos, que apresentou tetraplegia consequente à metástase medular cervical de carcinoma sólido mamário.

    PALAVRAS-CHAVES: Cão, neoplasia mamária, sistema nervoso central.

  4. Mammary Ductal Carcinoma In Situ: A Fresh Look at Architectural Patterns

    Directory of Open Access Journals (Sweden)

    Gabriel Scripcaru

    2012-01-01

    Full Text Available Mammary ductal carcinoma in-situ (DCIS, a malignant appearing lesion on cytological and histological grounds, is in fact a non-obligate precancer. DCIS is difficult to manage and is sometimes treated more aggressively than invasive carcinoma. Although most DCIS classifications take into account the architectural growth pattern, when it comes to architecture, the literature is full of contradictory information. We examined 289 breast cancers and found DCIS in 265 of the cases. The majority of the DCIS cases were seen in the setting of invasive cancer and only 9% of the cases represented pure DCIS with no invasive cancer. The DCIS commonly displayed a mixed pattern with micropapillary, cribriform and solid components with the micropapillary type being the rarest, occurring seldom on its own. A continuum of growth with a micropapillary pattern evolving into a cribriform type could be seen in some of the cases. This may explain some of the conflicting information, in the literature, regarding the different architectural types of DCIS. The comedo-pattern of necrosis could be seen in all types of DCIS. We therefore conclude that the study of the determinants of growth pattern in DCIS would be the key to unravelling the diverse, often non-concordant evidence one encounters in the literature.

  5. Finding and characterizing mammary analogue secretory carcinoma of the salivary gland.

    Science.gov (United States)

    Jung, Min Jung; Song, Joon Seon; Kim, Sang Yoon; Nam, Soon Yuhl; Roh, Jong-Lyel; Choi, Seung-Ho; Kim, Sung-Bae; Cho, Kyung-Ja

    2013-02-01

    A new tumor entity of the salivary glands, mammary analogue secretory carcinoma (MASC) with ETV6-NTRK3 translocation, has recently been proposed. MASC was originally diagnosed as adenocarcinoma, not otherwise specified (ANOS), or acinic cell carcinoma (AciCC) by the current World Health Organization classification. We aimed to identify MASC cases by molecular tests, and to characterize their clinical, histological, and immunohistochemical features. Thirty cases of MASC candidates were selected after review of 196 salivary gland tumors, and subjected to break-apart ETV6 fluorescence in situ hybridization (FISH), and immunohistochemical study for S100 protein, gross cystic disease fluid protein 15, DOG1, estrogen receptor, and progesterone receptor. Valid FISH results were obtained in 23 cases, and 13 positive cases were retrieved. MASCs were histologically varied, and the most frequent features observed in 10 cases were low-grade papillary/cystic/glandular patterns, intraluminal secretory materials, ovoid/wrinkled nuclei, and relatively abundant granular eosinophilic cytoplasms, corresponding to papillary-cystic or follicular types of AciCC. All cases showed diffuse immunopositivity for S100 protein. Three cases developed recurrences, but all patients remained alive. MASC could be a molecularly well-defined salivary gland neoplasm, encompassing some portions of AciCC and ANOS, but its histological spectrum and clinical implication require further investigation.

  6. Recuperative effect of Semecarpus anacardium linn. nut milk extract on carbohydrate metabolizing enzymes in experimental mammary carcinoma-bearing rats.

    Science.gov (United States)

    Sujatha, Venugopal; Sachdanandam, Panchanatham

    2002-03-01

    Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. We have tested the antitumour activity of Semecarpus anacardium nut extract against experimental mammary carcinoma in animals. As there is a direct relationship between the proliferation of tumour cells and the activities of the glycolytic and gluconeogenic enzymes, we studied changes in the activities of enzymes involved in this metabolic pathway in the liver and kidney. The enzymes investigated were glycolytic enzymes, namely hexokinase, phosphoglucoisomerase, aldolase and the gluconeogenic enzymes, namely glucose-6-phosphatase and fructose-1,6-biphosphatase in experimental rats. A significant rise in glycolytic enzyme activities and a simultaneous fall in gluconeogenic enzyme activities were found in mammary carcinoma bearing rats. Drug administration returned these enzyme activities to their respective control activities. Copyright 2002 John Wiley & Sons, Ltd.

  7. Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic study of 11 cases.

    Science.gov (United States)

    Din, Nasir Ud; Fatima, Saira; Kayani, Naila

    2016-06-01

    Mammary analogue secretory carcinoma (MASC) is a recently described tumor sharing the histologic, immunohistochemical, and molecular profile of secretory carcinoma of breast. We aimed to evaluate the morphologic and histochemical features needed/required for the diagnosis of MASC without adjunct of molecular analysis. Six retrospective cases suspicious for MASC and 5 prospective cases reported as MASC were included in the study. Molecular analysis of ETV6 by fluorescence in situ hybridization was performed at the University of Pittsburg, USA. The ages of the patients ranged from 9 to 60 years (mean, 27.5 years). Histologically, all tumors showed mixed growth patterns including microcystic, macrocystic, papillary, tubular, and solid, papillary the being most common pattern. The tumor cells showed round to oval vesicular nuclei with small nucleoli, and eosinophilic to vacuolated cytoplasm. All cases demonstrated luminal and cytoplasmic mucin on periodic acid-Schiff with and without diastase digestion and alcian blue stain. ETV6 fusion gene rearrangement by fluorescence in situ hybridization was detected in 10 of 11 tumors. Recurrences occurred in 3 patients, and 1 patient died of disease 5 years after surgery. In conclusion, MASC is a relatively rare salivary gland malignancy exhibiting distinct histologic and histochemical features which can help to differentiate it from other mimics. Histologically, papillary-cystic and microcystic patterns are the main clues to diagnosis. The follicular pattern of acinic cell carcinoma might represent MASC, as 4 cases in our series had this pattern. Two patients in our series were 9 and 9½ years old respectively, which are the youngest ages ever recorded for MASC. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Mammary analog secretory carcinoma of the parotid gland: A case report and literature review.

    Science.gov (United States)

    Balanzá, Ricardo; Arrangoiz, Rodrigo; Cordera, Fernando; Muñoz, Manuel; Luque-de-León, Enrique; Moreno, Eduardo; Toledo, Carlos; González, Edgar

    2015-01-01

    Background Mammary analog secretory carcinoma (MASC) was first described in 2010 by Skálová et al. This entity shares morphologic and immunohistochemical features with the secretory carcinoma (SC) of the breast. MASC usually presents as an asymptomatic mass in the parotid gland and predominantly affects men. This tumor is considered a low-grade carcinoma but has the potential for high-grade transformation. We report one MASC case and a review of world literature. Case report A 66-year-old male patient presented because he noticed a mass of approximately 3 × 3 cm on the right pre-auricular region. Physical examination demonstrated a 3 × 3.5 cm, firm, fixed, non-tender mass in the right pre-auricular region. An MRI of the head and neck showed an ovoid heterogeneous lesion, dependent of the right parotid gland of 27 × 28 mm. We performed a superficial parotidectomy with identification and preservation of the facial nerve. The immunophenotype was positive for epithelial membrane antigen (EMA), CK8/18, vimentin, S-100 protein, and mammoglobin. No further surgical interventions or adjuvant therapies were needed. The patient will have a close follow up. Conclusion The presence of t(12;15) (p13;q25) translocation which results in the ETV6-NTRK3 gene fusion or positive immunochemical studies for STAT5, mammoglobin and S100 protein, are necessary to confirm the diagnosis of MASC. MASC treatment should mimic the management of other low-grade malignant salivary gland neoplasms. The inhibition of ETV6-NTRK3 gene fusion could be used as treatment in the future. PMID:26496413

  9. Autocrine human growth hormone increases sensitivity of mammary carcinoma cell to arsenic trioxide-induced apoptosis.

    Science.gov (United States)

    Zekri, Ali; Ghaffari, Seyed H; Yousefi, Meysam; Ghanizadeh-Vesali, Samad; Mojarrad, Majid; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

    2013-09-05

    Human growth hormone (hGH) has been increasingly implicated in a variety of cancers; its up-regulation is observed in breast cancer and correlates with a poor outcome. Autocrine hGH promotes mammary carcinoma cell survival, proliferation, immortalization; it confers an invasive phenotype as a result of an epithelial-mesenchymal transition and contributes to chemoresistance and radioresistance. Arsenic trioxide (ATO) is being successfully used as a first and second line therapy for the treatment of patients with acute promyelocytic leukemia. It also inhibits tumor cell growth and induces apoptosis in a broad range of solid tumors. In the present study, we investigated the effect of hGH on sensitivity of a mammary adenocarcinoma cell to ATO, using a stable hGH-transfectant MCF-7 cell line, MCF7-hGH. Our results demonstrated for the first time that the overexpression of hGH increased sensitivity of the breast cancer cell line MCF-7 to ATO through apoptotic and anti-proliferative mechanisms. The effect of ATO on the transcriptional level of genes involved in survival (Bcl-2, Bax and Survivin), self-sufficiency in growth signals (c-Myc, ARF, Cdc25A, p53 and Bax), immortalization (hTERT) and invasion and metastasis (MMP-2 and MMP-9, uPA and uPAR and E-cadherin) was more pronounced in MCF7-hGH compared with its parental MCF-7 line. Our study may highlight the potential application of ATO for the treatment of patients with breast cancer, especially in those who have metastatic and chemoresistant tumor phenotype possibly due to the over expression of hGH. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. Ultrastructural Characterization of Mammary Analogue Secretory Carcinoma of the Salivary Glands: A Distinct Entity from Acinic Cell Carcinoma?

    Science.gov (United States)

    Guilmette, Julie; Nielsen, Gunnlaugur P; Faquin, William C; Selig, Martin; Nosé, Vânia; Chi, Anthony W S; Sadow, Peter M

    2017-02-13

    Mammary analogue secretory carcinoma (MASC) of the salivary glands is a recently described neoplasm of the salivary glands with a characteristic morphology complemented by a specific cytogenetic translocation and gene rearrangements. Although immunophenotypic and cytogenetic differences allow for a more reliable distinction, ultrastructural features can also provide important information about the relationship between MASC, classic acinic cell carcinoma (AciCC), and AciCC intercalated duct cell-predominant variant. Following approval from the hospital's institutional review board, 7 cases of MASC, 8 cases of classic AciCC, and 4 cases of AciCC intercalated duct cell-predominant variant were retrieved from the pathology files of Massachusetts General Hospital from 2012 to 2015. Electron microscopy was performed using formalin-fixed, paraffin-embedded tissue. Ultrastructural features of all 19 neoplasms of the salivary glands were recorded. The predominant cell-types observed in MASC are those with intercalated/striated duct cell differentiation. These features include prominent invaginations of the cell surface studded with microvilli, and some intra- and intercellular lumina also with a microvillous surface. Classic AciCC dominant cell-type recapitulates acinar cell differentiation. These cells contain large intracytoplasmic zymogen-like granules. AciCC intercalated duct cell-predominant variant showed both cell populations in various proportions with the intercalated/striated duct cell type usually being the dominant one. MASC presents with distinctive ultrastructural features that allows its proper differentiation from classic AciCC. However, significant ultrastructural features overlaps between both AciCC intercalated duct cells-predominant and classic AciCC and MASC. These findings indicate a very close proximity between these tumors.

  11. Unmasking MASC: bringing to light the unique morphologic, immunohistochemical and genetic features of the newly recognized mammary analogue secretory carcinoma of salivary glands.

    Science.gov (United States)

    Bishop, Justin A

    2013-03-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is characterized by its striking morphologic and molecular similarities to secretory carcinoma of the breast. This review highlights the characteristic clinical, histologic, immunophenotypic, and molecular features of MASC, and draws attention to the differential diagnosis of this increasingly recognized tumor.

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

    Science.gov (United States)

    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.

  13. Cytogenetic and immunohistochemical characterization of mammary analogue secretory carcinoma of salivary glands.

    Science.gov (United States)

    Khurram, Syed A; Sultan-Khan, Jemel; Atkey, Neil; Speight, Paul M

    2016-12-01

    Mammary analogue secretory carcinoma (MASC), initially considered a subset of acinic cell carcinoma (ACC), harbors an ETV6 translocation [t(12:15)(p13:25 q)] and is now regarded as a distinct entity. Several putative markers to differentiate MASC from ACC have been reported; however, the immunohistochemical profile is still being explored and updated. The purpose of this study was to further explore the cytogenetic and immunohistochemical profile of MASC. Cases were analyzed for ETV6 translocation using fluorescent in situ hybridization and stained for CK8, amylase, mammaglobin, GCDFP-15, MUC1, MUC4, STAT5a, Ki-67 (n = 37), CK7, Cam5.2, CK14, SMA, p63, S100, vimentin and DOG1 (n = 42). Histochemical stains for mucins were also performed and data collected for age, sex, and site. Fluorescent in situ hybridization showed 9 cases with ETV6 rearrangement and 2 with increased ETV6 copies. These 11 cases showed an absence of PAS-D-resistant granules, with 10 of 11 showing strong S100, mammaglobin, and STAT5a staining. All ACCs showed diffuse DOG1 staining, whereas 8/11 MASCs were negative and 3 showed only focal DOG1 staining. DOG1 can be used in conjunction with PAS-D, S100, and mammaglobin to identify MASCs. Cases with increased ETV6 copies are a novel finding with a similar immunostaining profile and should be considered as MASCs. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Most Non-Parotid “Acinic Cell Carcinomas” Represent Mammary Analogue Secretory Carcinomas

    Science.gov (United States)

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

    2013-01-01

    Acinic cell carcinoma (ACC) is a low grade salivary gland malignancy characterized by serous acinar differentiation. Most ACCs arise in the parotid gland, but ACCs have been reported to originate in non-parotid salivary glands where where serous acini are less abundant. Given the recent discovery of mammary analogue secretory carcinoma (MASC) – a salivary malignancy that histologically mimics ACC – a retrospective re-evaluation of non-parotid ACCs is warranted. The surgical pathology archives of The Johns Hopkins Hospital were searched for all ACCs arising outside of the parotid gland. For each case, the histologic slides were reviewed; immunohistochemistry (mammaglobin, S100 protein) was performed; and confirmatory ETV6 break-apart FISH assay was completed. Demographic and clinical data was obtained from the medical records. Fourteen extra-parotid tumors diagnosed as ACC were identified. Eleven of 14 (79%) tumors harbored the ETV6 translocation (oral cavity = 9 of 11; submandibular gland = 2 of 2). The translocation positive tumors occurred in 7 women and 4 men ranging in age from 20–86 years (mean, 56), and usually presented as painless masses. Immunohistochemistry for mammaglobin and S100 was positive in all 11 translocation positive tumors, but negative in the 3 translocation negative tumors. Histologically, the translocation positive tumors exhibited uniform cells with vacuolated cytoplasm, microcystic/cystic and papillary architecture, and intraluminal secretions; but the presence of basophilic cytoplasmic granules was conspicuously absent. Basophilic cytoplasmic granules, indicative of true serous acinar differentiation, were present in the 3 translocation negative tumors. Of the translocation positive tumors, only one locally recurred, and none metastasized. Most alleged ACCs of non-parotid origin actually represent misclassified MASCs. The impact of diagnostic error is mitigated by the low grade nature of MASC that, like ACCs, do not appear to be

  15. Ganciclovir uptake in human mammary carcinoma cells expressing herpes simplex virus thymidine kinase

    Energy Technology Data Exchange (ETDEWEB)

    Haberkorn, Uwe; Khazaie, Khashayarsha; Morr, Iris; Altmann, Annette; Mueller, Markus; Kaick, Gerhard van

    1998-05-01

    Assessment of suicide enzyme activity would have considerable impact on the planning and the individualization of suicide gene therapy of malignant tumors. This may be done by determining the pharmacokinetics of specific substrates. We generated ganciclovir (GCV)-sensitive human mammary carcinoma cell lines after transfection with a retroviral vector bearing the herpes simplex virus thymidine kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and phosphorylation than control cells, whereas in wild-type MCF7 cells no phosphorylated GCV was detected. In bystander experiments the total GCV uptake was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of GCV correlated closely with the growth inhibition (r=0.92). Therefore, the accumulation of specific substrates may serve as an indicator of the HSV-tk activity and of therapy outcome. Inhibition and competition experiments demonstrated slow transport of GCV by the nucleoside carriers. The slow uptake and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the nucleoside transport systems or for HSV-tk. This may be the limiting factor for therapy success, necessitating the search for better substrates of HSV-tk.

  16. Modifications of the thorax radiography after postoperative irradiation in mammary carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Scheier, M.; Rhomberg, W.; Schelling, F.

    1987-02-01

    The radiogenic modifications of the thorax radiography were evaluated in 100 patients irradiated postoperatively for mammary carcinoma between January, 1980 and March, 1983. No adjuvant chemotherapy was given. A telecobalt unit was used for the irradiations. A computer-assisted planning (Evados) was applied in order to obtain an individual optimization especially for the fields situated at the thoracic walls. The average focal doses to the thoracic wall and the regional lymph nodes were between 50 and 52 Gy. Taking into consideration all modifications visualized by radiography, 65% of patients had subacute radiogenic reactions in the lungs, especially in the apex fields. In general the modifications had no clinical importance. Only seven patients presented more severe forms of pneumonitis with clinical symptoms. Fibroses were developed only in the apex fields; infraclavicular infiltrations were seen only in exceptional cases. There were no costal necroses, essential pleural reactions, or radiogenic enlargements of the heart shadow. The rate of pulmonary reactions with clinical symptoms is reduced as compared with former techniques, e.g. opposing tangential fields. The knowledge of anamnesis and typical radiographic modifications should help to avoid problems of differentiation between apex reactions and tuberculosis.

  17. Bone scanning as a routine examination of patients with mammary carcinoma; a critical consideration. [Preoperative scanning

    Energy Technology Data Exchange (ETDEWEB)

    Heslinga, J.M.; Pauwels, E.K.J.; Zwaveling, A. (Rijksuniversiteit Leiden (Netherlands). Academisch Ziekenhuis)

    1982-06-05

    The usefulness of bone scanning as a routine examination was evaluated in 136 female patients with mammary carcinoma of whom 81 were staged as Columbia A and 55 as Columbia B/C. The preoperative bone scanning was positive in only 4 patients (2.9%). Consequently, bone scanning is no longer performed in the authors clinic for the preoperative detection of skeletal metastases. Bone scanning as a routine examination at 6-month intervals does not appear to be useful for the first 4 years of the follow-up, either. Most of the patients with a positive bone scan displayed other signs of skeletal metastases at the same time, such as ostealgia and a raised serum alkaline phosphatase level. Further increase of the frequency of bone scanning during the follow-up period would increase the costs considerably, almost prohibitively, even apart from the question whether such a measure might indeed significantly influence the patient's prognosis. The authors conclude that bone scanning should only be performed on the basis of the anamnesis, physical and laboratory findings, both prior to operation and during the follow-up period.

  18. Aspiration cytology of mammary analogue secretory carcinoma of the salivary gland.

    Science.gov (United States)

    Jung, Min Jung; Kim, Sang Yoon; Nam, Soon Yuhl; Roh, Jong-Lyel; Choi, Seung-Ho; Lee, Jeong Hyun; Baek, Jung Hwan; Cho, Kyung-Ja

    2015-04-01

    Aspiration cytologic findings of mammary analogue secretory carcinoma (MASC), a newly established salivary gland neoplasm defined by a t(12;15)(p13;q25) ETV6-NTRK3 translocation, are not fully characterized to date. We report cytologic descriptions of nine cases of molecularly confirmed MASC, including two with unusual findings. Aspiration smears from nine MASCs of the salivary glands were retrospectively reviewed and analyzed according to the cellular and structural features of the corresponding surgical specimens. Aspiration smears of MASC generally reflected the histologic diversity of the tumors. Among usual histologic findings, a micropapillary pattern was associated with a predominance of vacuolated individual cells on aspiration smears, a papillary-cystic pattern with a predominance of thin branching papillary structures, and a microcystic pattern with a predominance of irregular sheets of eosinophilic cells. There were two unusual cases, one with three-dimensional groups of high-grade atypical cells, and one with epithelial clusters floating in a notably mucinous background. These cases represented MASC with high-grade transformation and MASC with cystadenocarcinoma-like features, respectively. The secretory activity of MASC was not prominent in the aspiration specimens. Although unusual cases were present, most MASC cases showed characteristic cytologic findings, which could aid the cytologic diagnosis of MASC. And knowledge of the histologic spectrum of MASC, including high-grade transformation, could be valuable for cytological differential diagnoses of salivary gland tumors, and the management of patients with MASC. © 2014 Wiley Periodicals, Inc.

  19. Morphology in conjunction with immunohistochemistry is sufficient for the diagnosis of mammary analogue secretory carcinoma.

    Science.gov (United States)

    Shah, Akeesha A; Wenig, Bruce M; LeGallo, Robin D; Mills, Stacey E; Stelow, Edward B

    2015-03-01

    The recently described mammary analogue secretory carcinoma (MASC) is a low-grade salivary gland malignancy that harbors the recurrent cytogenetic abnormality t(12;15) (p13;q25) ETV6-NTRK3. Confirmation of this is currently considered the gold standard for diagnosis. Some have postulated that morphology together with supporting immunohistochemistry is sufficient to diagnose MASC. In this study we retrospectively review a series of 19 MASCs diagnosed based on histology in conjunction with immunohistochemistry; subsequently we performed in situ hybridization using an ETV6 break-apart probe. Immunohistochemistry for S100 protein and mammaglobin as well as fluorescence in situ hybridization using the Vysis ETV6 Dual Color Break-Apart FISH Probe Kit were performed on all cases. The 19 cases were from 12 females and 7 males with ages ranging from 16 to 76 years (mean = 45 years). Sixteen cases were from the parotid gland, 1 case was from a periparotid lymph node and 2 cases were from the submandibular gland. All 19 cases demonstrated moderate to strong expression of S100 protein. Eighteen cases demonstrated strong, diffuse expression of mammaglobin, while one case had only rare tumor cells that strongly expressed mammaglobin. Eighteen of 19 cases (95 %) demonstrated the ETV6 rearrangement by fluorescence in situ hybridization. Given that morphology together with immunohistochemistry is highly correlated with the ETV6 gene rearrangement, we conclude that molecular confirmation is not required to diagnose MASC.

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

    Science.gov (United States)

    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.

  1. 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.

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Mammary Analog Secretory Carcinoma (MASC) Involving the Thyroid Gland: A Report of the First 3 Cases.

    Science.gov (United States)

    Dettloff, Jennifer; Seethala, Raja R; Stevens, Todd M; Brandwein-Gensler, Margaret; Centeno, Barbara A; Otto, Kristen; Bridge, Julia A; Bishop, Justin A; Leon, Marino E

    2017-06-01

    Salivary gland-type tumors have been rarely described in the thyroid gland. Mammary Analog Secretory Carcinoma (MASC) is a recently defined type of salivary gland carcinoma characterized by a t(12;15)(p13;q25) resulting in an ETV6-NTRK3 fusion gene. We report 3 cases of MASC involving the thyroid gland without clinical evidence of a salivary gland or breast primary; the clinico-pathologic characteristics are reviewed. Assessment for rearrangement of the ETV6 (12p13) locus was conducted by fluorescence in situ hybridization (FISH) on representative FFPE sections using an ETV6 break apart probe (Abbott Molecular, Des Plaines, IL, USA). The patients were two females (52 and 55 years-old) and 1 male (74 years-old). The tumors were poorly circumscribed solid white tan nodules involving the thyroid. Histologically, they were invasive and showed solid, microcystic, cribriform, and tubular growth patterns composed of variably bland polygonal eosinophilic cells with vesicular nuclear chromatin and conspicuous nucleoli. All three cases showed metastasis to lymph nodes; one case showed lateral neck involvement. The tumor cells were positive for S100 and mammaglobin. GATA-3 and PAX-8 were positive in 2 cases, one of which only focally so. All three cases were negative for TTF-1 and thyroglobulin. Rearrangement of the ETV6 locus was confirmed in all cases and a diagnosis of MASC rendered for each case. A site of origin distinct from the thyroid gland was not identified, with a median follow up of 24 months. MASC may rarely involve the thyroid gland. The origin of these lesions is unknown; while an origin from ectopic salivary gland-type cells is entertained, a metastatic origin from an occult primary cannot be definitively excluded at this time. Given the histologic (follicular-like microcystic pattern with colloid-like secretions and papillary pattern), immunophenotypic (PAX-8), and even molecular overlap, MASC can be mistaken for papillary thyroid carcinoma and should be

  3. Carbonic anhydrase VI: a novel marker for salivary serous acinar differentiation and its application to discriminate acinic cell carcinoma from mammary analogue secretory carcinoma of the salivary gland.

    Science.gov (United States)

    Hsieh, Min-Shu; Jeng, Yung-Ming; Jhuang, Yu-Lin; Chou, Yueh-Hung; Lin, Chiao-Ying

    2016-04-01

    Carbonic anhydrase VI (CA6) is present in serous acinar cells of human salivary glands. The aim of this study was to investigate the diagnostic utility of CA6 in differentiating acinic cell carcinoma (AciCC) from its morphological mimic mammary analogue secretory carcinoma (MASC) of the salivary gland. CA6 immunostaining was performed in 28 cases of AciCC and 14 cases of MASC. All cases of AciCC showed positive CA6 staining. The staining pattern correlated with the number of serous acinar cells in tumours. All MASCs stained negatively for CA6. The results were compared with those obtained with currently used markers, including DOG1, mammaglobin, S100, and vimentin. CA6 showed sensitivity and specificity as high as those of DOG1 in diagnosing AciCC. CA6 expression was focally observed in basal cell adenoma and in one case of cystadenocarcinoma (1/3), but not in other salivary gland tumours, including mucoepidermoid carcinoma, adenoid cystic carcinoma, salivary duct carcinoma, lymphoepithelial carcinoma, epithelial-myoepithelial carcinoma, and pleomorphic adenoma. CA6 is a specific marker for serous acinar cells of salivary glands and AciCC. CA6 has sensitivity and specificity equal to those of DOG1 in the differential diagnosis between AciCC and MASC. A combination of CA6 and DOG1 could be an ideal immunohistochemical panel for AciCC. © 2015 John Wiley & Sons Ltd.

  4. 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.

    Science.gov (United States)

    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.

  5. Triple-negative vimentin-positive heterogeneous feline mammary carcinomas as a potential comparative model for breast cancer.

    Science.gov (United States)

    Caliari, Diego; Zappulli, Valentina; Rasotto, Roberta; Cardazzo, Barbara; Frassineti, Federica; Goldschmidt, Michael H; Castagnaro, Massimo

    2014-09-25

    Human breast cancer is a heterogeneous disease classified by molecular subtyping into luminal A, luminal B, HER2-overexpressing, basal-like, claudin-low and normal-breast like. The routinely applied and standardized immunohistochemical-based surrogates of this classification group together the last three entities as triple-negative breast cancer (TNBCs) that show the most diverse and complex heterogeneity and represent a therapeutic challenge. In the present work 156 feline mammary lesions consisting of feline mammary carcinomas (FMCs), benign neoplasms, and hyperplastic/dysplastic tissues were evaluated histologically and by immunohistochemistry for expression of basal and luminal cytokeratins (CK), vimentin, alpha-smooth muscle actin, calponin, estrogen receptor (ER) alpha (a), and progesterone receptor (PR). Thirty-seven FMCs with 27 matched non-neoplastic controls were also investigated for gene expression of ERa, ER beta, PR, and HER2. A large group of hormone receptors (HRs)-negative aggressive carcinomas - that did not overexpress HER2 - could be distinguished from the less aggressive (10.8%) and benign (8%) HRs + tumors, that showed bilineage (luminal and myoepithelial) differentiation. Immunohistochemical evaluations of cytoplasmic filaments indicated that HRs- FMCs are vimentin+, CK14+, and CK5_6+ carcinomas that may resemble the TNBCs (basal like/claudin low) described in women. The identification of luminal and myoepithelial progenitors within the mammary ductal system suggested potential cells/sites of origin of these tumors. A diffuse and never previously described CKs/vimentin luminal cell co-expression was detected in the non-neoplastic ducts, indicating a potential bilineage progenitor. These results indicate and potentially explain the high incidence of triple-negative, vimentin + aggressive tumors in cats that may used to elucidate some of the challenging features of TNBCs in women.

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

    Science.gov (United States)

    Estrela-Lima, Alessandra; Araújo, Márcio S S; Costa-Neto, João M; Teixeira-Carvalho, Andréa; Barrouin-Melo, Stella M; Cardoso, Sergio V; Martins-Filho, Olindo A; Serakides, Rogéria; Cassali, Geovanni D

    2010-06-04

    The immune system plays an important role in the multifactorial biologic system during the development of neoplasias. However, the involvement of the inflammatory response in the promotion/control of malignant cells is still controversial, and the cell subsets and the mechanisms involved are poorly investigated. The goal of this study was to characterize the clinical-pathological status and the immunophenotyping profile of tumor infiltrating lymphocytes and their association with the animal survival rates in canine mammary carcinomas. Fifty-one animals with mammary carcinomas, classified as carcinomas in mixed tumors-MC-BMT = 31 and carcinomas-MC = 20 were submitted to systematic clinical-pathological analysis (tumor size; presence of lymph node and pulmonary metastasis; clinical stage; histological grade; inflammatory distribution and intensity as well as the lymphocytic infiltrate intensity) and survival rates. Twenty-four animals (MC-BMT = 16 and MC = 8) were elected to the immunophenotypic study performed by flow cytometry. Data analysis demonstrated that clinical stage II-IV and histological grade was I more frequent in MC-BMT as compared to MC. Univariate analysis demonstrated that the intensity of inflammation (moderate/intense) and the proportion of CD4+ (> or = 66.7%) or CD8+ T-cells ( or = 600 (P = 0.02) remained as independent prognostic factor. Despite the clinical manifestation, the lymphocytes represented the predominant cell type in the tumor infiltrate. The percentage of T-cells was higher in animals with MC-BMT without metastasis, while the percentage of B-lymphocytes was greater in animals with metastasized MC-BMT (P carcinomas.

  7. Pineapple bromelain induces autophagy, facilitating apoptotic response in mammary carcinoma cells.

    Science.gov (United States)

    Bhui, Kulpreet; Tyagi, Shilpa; Prakash, Bharti; Shukla, Yogeshwer

    2010-01-01

    Bromelain, from pineapple, possesses potent anticancer effects. We investigated autophagic phenomenon in mammary carcinoma cells (estrogen receptor positive and negative) under bromelain treatment and also illustrated the relationship between autophagy and apoptosis in MCF-7 cells. MCF-7 cells exposed to bromelain showed delayed growth inhibitory response and induction of autophagy, identified by monodansylcadaverine localization. It was succeeded by apoptotic cell death, evident by sub-G1 cell fraction and apoptotic features like chromatin condensation and nuclear cleavage. 3-Methyladenine (MA, autophagy inhibitor) pretreatment reduced the bromelain-induced autophagic level, also leading to decline in apoptotic population, indicating that here autophagy facilitates apoptosis. However, addition of caspase-9 inhibitor Z-LEHD-FMK augmented the autophagy levels, inhibited morphological apoptosis but did not prevent cell death. Next, we found that bromelain downregulated the phosphorylation of extracellular signal-regulated kinase ½ (ERK½), whereas that of c-jun N-terminal kinase (JNK) and p38 kinase were upregulated. Also, MA had no influence on bromelain-suppressed ERK½ activation, yet, it downregulated JNK and p38 activation. Also, addition of mitogen-activated protein kinase (MAPK) inhibitors enhanced the autophagic ratios, which suggested the role of MAP kinases in bromelain-induced autophagy. All three MAPKs were seen to be constantly activated over the time. Bromelain was seen to induce the expressions of autophagy-related proteins, light chain 3 protein B II (LC3BII), and beclin-1. Using ERK½ inhibitor, expressions of LC3BII and beclin-1 increased, whereas p38 and JNK inhibitors decreased this protein expression, indicating that bromelain-induced autophagy was positively regulated by p38 and JNK but negatively regulated by ERK½. Autophagy-inducing property of bromelain can be further exploited in breast cancer therapy. Copyright © 2010 International Union

  8. A unique case of a cutaneous lesion resembling mammary analog secretory carcinoma: a case report and review of the literature.

    Science.gov (United States)

    Albus, Jennifer; Batanian, Jacqueline; Wenig, Bruce M; Vidal, Claudia I

    2015-04-01

    Mammary analog secretory carcinoma (MASC) is a rare type of salivary gland tumor named for its morphological and genetic similarity to secretory carcinoma of the breast. These tumors are most often found in the parotid gland but have been described in several other mucosal locations of the head and neck. In this case report, a cutaneous lesion most closely resembling MASC was found in a neck mass of a 64-year-old male patient without evidence of a primary salivary gland or oral tumor. The lesion was excised, and the patient remains disease free to date. This case depicts a rare tumor in the skin most closely mimicking MASC and brings additional awareness to dermatopathologists of this tumor.

  9. Mammary-specific inactivation of E-cadherin and p53 impairs functional gland development and leads to pleomorphic invasive lobular carcinoma in mice

    Directory of Open Access Journals (Sweden)

    Patrick W. B. Derksen

    2011-05-01

    Breast cancer is the most common malignancy in women of the Western world. Even though a large percentage of breast cancer patients show pathological complete remission after standard treatment regimes, approximately 30–40% are non-responsive and ultimately develop metastatic disease. To generate a good preclinical model of invasive breast cancer, we have taken a tissue-specific approach to somatically inactivate p53 and E-cadherin, the cardinal cell-cell adhesion receptor that is strongly associated with tumor invasiveness. In breast cancer, E-cadherin is found mutated or otherwise functionally silenced in invasive lobular carcinoma (ILC, which accounts for 10–15% of all breast cancers. We show that mammary-specific stochastic inactivation of conditional E-cadherin and p53 results in impaired mammary gland function during pregnancy through the induction of anoikis resistance of mammary epithelium, resulting in loss of epithelial organization and a dysfunctional mammary gland. Moreover, combined inactivation of E-cadherin and p53 induced lactation-independent development of invasive and metastatic mammary carcinomas, which showed strong resemblance to human pleomorphic ILC. Dissemination patterns of mouse ILC mimic the human malignancy, showing metastasis to the gastrointestinal tract, peritoneum, lung, lymph nodes and bone. Our results confirm that loss of E-cadherin contributes to both mammary tumor initiation and metastasis, and establish a preclinical mouse model of human ILC that can be used for the development of novel intervention strategies to treat invasive breast cancer.

  10. A Case of Primary Mammary Analog Secretory Carcinoma (MASC) of the Thyroid Masquerading as Papillary Thyroid Carcinoma: Potentially More than a One Off.

    Science.gov (United States)

    Reynolds, S; Shaheen, M; Olson, G; Barry, M; Wu, J; Bocklage, T

    2016-09-01

    We present the second reported mammary analog secretory carcinoma (MASC) apparently arising in the thyroid and propose a potential close relationship to ETV6-NTRK3 fusion papillary thyroid carcinoma. The patient, a 36 year old woman, presented with a neck mass of 1 year's duration. Imaging studies showed a tumor involving most of the thyroid with enlarged regional lymph nodes. FNA biopsy yielded a diagnosis of "papillary thyroid carcinoma". Resection revealed a 4.5 cm infiltrative tumor. Final diagnosis was "papillary thyroid carcinoma (PTC) consistent with diffuse sclerosing variant" with positive lymph nodes (2+/4) and margins. Histologic features included mixed microcystic, solid, follicular and papillary architecture, prominent nucleoli, abundant nuclear grooves and rare nuclear pseudo-inclusions. Despite radioactive iodine, radiotherapy and multiagent chemotherapy, the patient progressed over 6 years with local recurrence and additional lymph node involvement finally developing widespread distant metastases. Prompted by the breast carcinoma-like histopathology of a metastasis, immunohistochemical staining was performed and revealed strong expression of GATA3 and mammaglobin with no reactivity for thyroglobulin or TTF-1. The original tumor was then tested and showed the same immunoprofile. RT-PCR confirmed the presence of an ETV6-NTRK3 fusion consistent with a diagnosis of MASC. Our patient's clinical, imaging and morphologic features remarkably mimicked papillary thyroid carcinoma. At the molecular level, the ETV6-NTRK3 fusion in this patient involved exons reported in the rare "papillary thyroid carcinoma" with this translocation. Given the immunophenotype of this case, it is possible that at least some ETV6-NTRK3 fusion positive PTC are actually MASC masquerading as papillary thyroid carcinoma.

  11. ARTEMIN promotes de novo angiogenesis in ER negative mammary carcinoma through activation of TWIST1-VEGF-A signalling.

    Directory of Open Access Journals (Sweden)

    Arindam Banerjee

    Full Text Available The neurotrophic factor ARTEMIN (ARTN has been reported to possess a role in mammary carcinoma progression and metastasis. Herein, we report that ARTN modulates endothelial cell behaviour and promotes angiogenesis in ER-mammary carcinoma (ER-MC. Human microvascular endothelial cells (HMEC-1 do not express ARTN but respond to exogenously added, and paracrine ARTN secreted by ER-MC cells. ARTN promoted endothelial cell proliferation, migration, invasion and 3D matrigel tube formation. Angiogenic behaviour promoted by ARTN secreted by ER-MC cells was mediated by AKT with resultant increased TWIST1 and subsequently VEGF-A expression. In a patient cohort of ER-MC, ARTN positively correlated with VEGF-A expression as measured by Spearman's rank correlation analysis. In xenograft experiments, ER-MC cells with forced expression of ARTN produced tumors with increased VEGF-A expression and increased microvessel density (CD31 and CD34 compared to tumors formed by control cells. Functional inhibition of ARTN by siRNA decreased the angiogenic effects of ER-MC cells. Bevacizumab (a humanized monoclonal anti-VEGF-A antibody partially inhibited the ARTN mediated angiogenic effects of ER-MC cells and combined inhibition of ARTN and VEGF-A by the same resulted in further significant decrease in the angiogenic effects of ER-MC cells. Thus, ARTN stimulates de novo tumor angiogenesis mediated in part by VEGF-A. ARTN therefore co-ordinately regulates multiple aspects of tumor growth and metastasis.

  12. Combined DOG1 and Mammaglobin Immunohistochemistry Is Comparable to ETV6-breakapart Analysis for Differentiating Between Papillary Cystic Variants of Acinic Cell Carcinoma and Mammary Analogue Secretory Carcinoma.

    Science.gov (United States)

    Said-Al-Naief, Nasser; Carlos, Roman; Vance, Gail H; Miller, Caroline; Edwards, Paul C

    2017-04-01

    We investigated the reliability of combined DOG1 and mammaglobin immunohistochemistry compared with ETV6 fluorescence in situ hybridization (FISH) in the assessment of salivary tumors previously diagnosed as acinic cell carcinoma (ACC). Ultrastructural features of cases reclassified as mammary analogue secretory carcinoma (MASC) were assessed by transmission electron microscopy (TEM). Immunohistochemical (IHC) reactivity to DOG1 and mammaglobin was validated against FISH targeting the ETV6 gene in all 14 cases. Three cases with papillary cystic histomorphology previously diagnosed as ACC were revised to MASC. TEM features of the ETV6 rearrangement-positive MASC cases showed large numbers of secretory granules with extrusion into the intercellular spaces, well-developed endoplasmic reticulum, lipid-laden vacuoles, well-formed microvilli, and large lining cystic spaces. Combined DOG1 and mammaglobin immunohistochemistry is comparable to ETV6 -breakapart analysis for differentiating between papillary cystic variants of ACC and MASC.

  13. PTEN Loss in E-Cadherin-Deficient Mouse Mammary Epithelial Cells Rescues Apoptosis and Results in Development of Classical Invasive Lobular Carcinoma

    NARCIS (Netherlands)

    Boelens, M.C.; Nethe, M.; Klarenbeek, S.; de Ruiter, J.R.; Schut, E.; Bonzanni, N.; Zeeman, A.L.; Wientjens, E.; van der Burg, E.; Wessels, L.; van Amerongen, R.; Jonkers, J.

    2016-01-01

    Invasive lobular carcinoma (ILC) is an aggressive breast cancer subtype with poor response to chemotherapy. Besides loss of E-cadherin, a hallmark of ILC, genetic inactivation of PTEN is frequently observed in patients. Through concomitant Cre-mediated inactivation of E-cadherin and PTEN in mammary

  14. The Immunoexpression of Glucocorticoid Receptors in Breast Carcinomas, Lactational Change, and Normal Breast Epithelium and Its Possible Role in Mammary Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Raja Alyusuf

    2017-01-01

    Full Text Available The role of estrogen and progesterone receptors in breast cancer biology is well established. In contrast, other steroid hormones are less well studied. Glucocorticoids (GCs are known to play a role in mammary development and differentiation; thus, it is of interest to attempt to delineate their immunoexpression across a spectrum of mammary epithelia. Aim. To delineate the distribution pattern of glucocorticoid receptors (GRs in malignant versus nonmalignant epithelium with particular emphasis on lactational epithelium. Materials and Methods. Immunohistochemistry (IHC for GRs was performed on archival formalin-fixed paraffin-embedded tissue blocks of 96 cases comprising 52 invasive carcinomas, 21 cases with lactational change, and 23 cases showing normal mammary tissue histology. Results. Results reveal an overexpression of GRs in mammary malignant epithelium as compared to both normal and lactational groups individually and combined. GR overexpression is significantly more pronounced in HER-2-negative cancers. Discussion. This is the first study to compare GR expression in human lactating epithelium versus malignant and normal epithelium. The article discusses the literature related to the pathobiology of GCs in the breast with special emphasis on breast cancer. Conclusion. The lactational epithelium did not show overexpression of GR, while GR was overexpressed in mammary NST (ductal carcinoma, particularly HER-2-negative cancers.

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

    Science.gov (United States)

    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

  16. Mammary analogue secretory carcinoma of salivary gland origin: an update and expanded morphologic and immunohistochemical spectrum of recently described entity.

    Science.gov (United States)

    Skalova, Alena

    2013-07-01

    Mammary analogue secretory carcinoma of salivary gland origin (MASC) is a recently described tumor with ETV6 translocation. Akin to secretory breast cancer, MASC expresses S-100 protein, mammaglobin, vimentin, and harbors a t(12;15) (p13;q25) translocation which leads to ETV6-NTRK3 fusion product. Histologically, MASC displays a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogeneous or bubbly secretions. Colloid-like secretory material stains positive for periodic acid-Schiff (PAS) with and without diastase and for Alcian blue. The cells of MASC are devoid of PAS-positive secretory zymogen granules. These features help to exclude the most important differential diagnostic considerations, namely acinic cell carcinoma, low-grade cribriform cystadenocarcinoma, cystadenocarcinoma (not otherwise specified), and low-grade mucoepidermoid carcinoma. To date the presence of the ETV6-NTRK3 fusion gene has not been demonstrated in any other salivary gland tumor than MASC. It is likely that MASC is more common than currently recognized and with further studies, the clinical need for molecular studies of the ETV6-NTRK3 fusion may diminish. However, molecular testing is recommended at this time to arrive at the diagnosis of MASC.

  17. Investigations on hormone dependency of human mammary carcinomas transplanted into nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M

    1981-01-01

    Since human mammary cancer can be transplanted into nude mice, this makes possible the in vivo study of relations between hormone dependency and the steroid hormone receptor content of the tumors. The macroscopic growth curve of the transplanted tumors during endocrine therapy will reflect...... the hormone dependency. The results can be compared with successive steroid hormone receptor determinations in the tumor tissue....

  18. Gene expression profiles in canine mammary carcinomas of various grades of malignancy

    NARCIS (Netherlands)

    Pawlowski, K.M.; Maciejewski, R.; Dolka, I.; Mol, B.W.J.

    2013-01-01

    Abstract Background The frequency of mammary malignancies in canine patients is even three times over than in human. In various types of cancer different intracellular signalling pathways are perturbed, thus the patients with pathologically the same type of cancer often have dissimilar genetic

  19. Adaptation of Laser Microdissection Technique to Nanostring RNA Analysis in the Study of a Spontaneous Metastatic Mammary Carcinoma Mouse Model.

    Science.gov (United States)

    Castro, Nadia P; Golubeva, Yelena G

    2018-01-01

    The mouse model characterized by spontaneous lung metastasis from JygMC (A) cells closely resembles the human triple negative breast cancer (TNBC) subtype. The primary tumors morphologically present both epithelial and spindle-like cells, but metastases in lung parenchyma display only adenocarcinoma properties. In the study of molecular signatures, laser capture microdissection (LCM) on frozen tissue sections was used to separate the following regions of interest: the epithelial-mesenchymal transition (EMT), mesenchymal-epithelial transition (MET), carcinoma, lung metastases, normal mammary gland and normal lung parenchyma. NanoString was selected for the study of molecular signatures in LCM targets as a reliable downstream gene expression platform allowing analysis of tissue lysates without RNA extraction and amplification. This chapter provides detailed protocols for the collection of tissue, LCM sample preparation and dissection, production of lysates, extraction, and quality control of RNA for NanoString analysis, as well as the methodology of Nanostring gene expression profiling experiment.

  20. Mammary Analogue Secretory Carcinoma of the Parotid Gland: A Third World Country Perspective-A Case Series.

    Science.gov (United States)

    Salat, Huzaifah; Mumtaz, Ramiz; Ikram, Mubasher; Din, Nasir Ud

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) is a recently described pathological entity in major salivary glands, which was first described by Skálová et al. in 2010. Since then only a limited number of case reports/series have been published describing this tumor with the majority of them discussing the genetic and cytoarchitectural aspect of this tumor. Keeping this in view with the lack of clinical correlation with regard to this tumor, we present our approach to management of two such cases which, according to the best of our knowledge, are the first 2 cases presenting in the South Asian continent. Both patients were diagnosed and managed at Aga Khan University Hospital, Karachi, Pakistan.

  1. Mammary Analogue Secretory Carcinoma of the Parotid Gland: A Third World Country Perspective—A Case Series

    Science.gov (United States)

    Salat, Huzaifah; Mumtaz, Ramiz; Ikram, Mubasher; Din, Nasir Ud

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) is a recently described pathological entity in major salivary glands, which was first described by Skálová et al. in 2010. Since then only a limited number of case reports/series have been published describing this tumor with the majority of them discussing the genetic and cytoarchitectural aspect of this tumor. Keeping this in view with the lack of clinical correlation with regard to this tumor, we present our approach to management of two such cases which, according to the best of our knowledge, are the first 2 cases presenting in the South Asian continent. Both patients were diagnosed and managed at Aga Khan University Hospital, Karachi, Pakistan. PMID:26783481

  2. Mammary Analogue Secretory Carcinoma of the Parotid Gland: A Third World Country Perspective—A Case Series

    Directory of Open Access Journals (Sweden)

    Huzaifah Salat

    2015-01-01

    Full Text Available Mammary analogue secretory carcinoma (MASC is a recently described pathological entity in major salivary glands, which was first described by Skálová et al. in 2010. Since then only a limited number of case reports/series have been published describing this tumor with the majority of them discussing the genetic and cytoarchitectural aspect of this tumor. Keeping this in view with the lack of clinical correlation with regard to this tumor, we present our approach to management of two such cases which, according to the best of our knowledge, are the first 2 cases presenting in the South Asian continent. Both patients were diagnosed and managed at Aga Khan University Hospital, Karachi, Pakistan.

  3. Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic and molecular study including 2 cases harboring ETV6-X fusion.

    Science.gov (United States)

    Ito, Yohei; Ishibashi, Kenichiro; Masaki, Ayako; Fujii, Kana; Fujiyoshi, Yukio; Hattori, Hideo; Kawakita, Daisuke; Matsumoto, Manabu; Miyabe, Satoru; Shimozato, Kazuo; Nagao, Toshitaka; Inagaki, Hiroshi

    2015-05-01

    Mammary analogue secretory carcinoma (MASC) is a recently described low-grade carcinoma with morphologic and genetic similarity, including ETV6-NTRK3 fusion, to secretory carcinoma of the breast. ETV6 is frequently involved in other epithelial and nonepithelial tumors, and many fusion partners of ETV6 have been reported. In the present study, 14 Japanese MASC cases were clinicopathologically and molecularly analyzed. The median age of the patients was 39 years, and the male:female ratio was 6:8. All cases showed histopathologic findings compatible with those previously described for MASC and harbored an ETV6 split as visualized by fluorescence in situ hybridization. Two cases showed thick fibrous septa and invasive features including vascular or perineural tumor involvement, findings that are rare in MASC. In addition, in these 2 cases, non-NTRK3 genes appeared to fuse with ETV6 (ETV6-X fusion). NTRK1 and NTRK2, both members of the NTRK family, were not involved. Of the 14 MASC cases, the ETV6-NTRK3 fusion transcript was positive in 6 cases, and the relative expression level of the ETV6-NTRK3 fusion transcript was variable, ranging from 1 to 5.8. Results of the present study of MASC suggest that (1) ETV6 occasionally fuses with unknown non-NTRK3 genes, (2) ETV6-X cases might have an invasive histology, (3) for molecular diagnosis of MASC, fluorescence in situ hybridization to detect ETV6 splits is the method of choice, and (4) the expression level of the ETV6-NTRK3 fusion transcript is considerably variable. These findings provide a novel insight into the oncogenesis, histopathology, diagnosis, treatment, and prognosis of this newly recognized carcinoma.

  4. Effect of an Extract of Withania somnifera Root on Estrogen Receptor-positive Mammary Carcinomas

    Science.gov (United States)

    KHAZAL, KAMEL F.; SAMUEL, TEMESGEN; HILL, DONALD L.; GRUBBS, CLINTON J.

    2013-01-01

    The chemopreventive activity of an extract of Withania somnifera (WS) roots was examined in female Sprague-Dawley rats that received the mammary carcinogen methylnitrosourea (MNU). The dose of the extract, administered by gavage, was 150 mg/kg body weight daily for 155 days after injection of MNU. Rats in the treated group (N=15) had an average of 3.47 tumors, and rats in the control group (N=15) had 4.53, a reduction of 23%. The average weights of tumors were 4.98 g for rats in the treated group and 6.30 g for the controls, a difference of 21%. Labeling indices for Ki67 and proliferating cell nuclear antigen (PCNA) markers in cancers of the treated group were 42% and 38% lower, respectively, than those of the corresponding indices for the control group. These results indicate that the root extract significantly reduced the rate of cell division in the mammary tumors. PMID:23564793

  5. Prognostic evaluation of feline mammary carcinomas: a review of the literature.

    Science.gov (United States)

    Zappulli, V; Rasotto, R; Caliari, D; Mainenti, M; Peña, L; Goldschmidt, M H; Kiupel, M

    2015-01-01

    A large number of studies have investigated feline mammary tumors in an attempt to identify prognostic markers and generate comparative analyses with human breast cancer. Nevertheless, a retrospective base of assessments and the lack of standardization in methodology and study design have caused weakness in study results, making comparison difficult. We examined feline mammary tumor publications and evaluated postulated prognostic parameters according to the recently published "Recommended Guidelines for the Conduct and Evaluation of Prognostic Studies in Veterinary Oncology." Using these criteria, we determined with statistically significant reliability that prognostic parameters for feline mammary tumors are tumor grading and lymph node/lymphovascular invasion. Furthermore, tumor subtype, size, and staging are worthy of further standardized investigation. We present statistical significance for each studied parameter as well as its relevance to disease progression and survival. Our evaluation suggests that marker expression (ie, Ki67, HER2, ER) may provide relevant information applicable for therapeutic predictions; however, consensus efforts and protocol standardization are needed. We identify and discuss major points of concern--such as sample preservation and selection, standardization of immunohistochemical protocols, and evaluation of results--to provide support for subsequent reliable analyses. © The Author(s) 2014.

  6. Mammary analogue secretory carcinoma of salivary glands is a lipid-rich tumour, and adipophilin can be valuable in its identification.

    Science.gov (United States)

    Mariano, Fernanda Viviane; dos Santos, Harim Tavares; Azañero, Wilson Delgado; da Cunha, Isabela Werneck; Coutinho-Camilo, Claudia Malheiros; de Almeida, Oslei Paes; Kowalski, Luiz Paulo; Altemani, Albina

    2013-10-01

    Mammary analogue secretory carcinoma (MASC) of salivary glands shows morphological similarities to milk-secreting mammary epithelial cells. The aim of this study was to analyse the immunohistochemical expression of adipophilin (a component of milk lipid globule membranes) and of proteins related to secretory mechanisms (STAT5a and mammaglobin) in MASC and other salivary tumours. Ten cases of MASC (all with ETV6 translocation) and 83 other salivary carcinomas were studied. In all MASC cases, adipophilin stained numerous large lipid droplets. These droplets were minute in other salivary carcinomas, except for sebaceous carcinoma. Overexpression of STAT5a was detected in all MASC cases, but only occasionally in other carcinomas. Mammaglobin expression occurred frequently in MASC (70% of cases), whereas, in other carcinomas, it was uncommon and limited. Only MASC showed cytoplasmic reactivity for p63, particularly in papillary-cystic areas. Positivity for S100, vimentin and high molecular weight keratin was observed in 100% of MASC cases. MASC is a lipid-rich tumour containing large lipid droplets covered by adipophilin. This finding can be included among its defining immunohistochemical features, and possibly represents lactation-like secretory differentiation. Strong expression of STAT5a and cytoplasmic p63 in MASC reinforces this hypothesis. © 2013 John Wiley & Sons Ltd.

  7. Detection in human breast carcinomas of an antigen immunologically related to a group-specific antigen of mouse mammary tumor virus.

    Science.gov (United States)

    Mesa-Tejada, R; Keydar, I; Ramanarayanan, M; Ohno, T; Fenoglio, C; Spiegelman, S

    1978-03-01

    An antigen immunologically related to a group-specific antigen (gp52, a 52,000-dalton glycoprotein) of the mouse mammary tumor virus has been identified in paraffin sections of human breast cancers by means of the indirect immunoperoxidase technique. The specificity of the reaction with antibody against mouse mammary tumor virus was examined by absorption of the IgG with the following: (a) purified gp52; (b) a number of virus preparations (mouse mammary tumor virus, Rauscher leukemia virus, simian sarcoma virus, baboon endogenous virus, and Mason-Pfizer monkey virus); (c) normal plasma, leukocytes, breast tissue, milk, actin, collagen, and hyaluronic acid, all of human origin; (d) sheep erythrocytes and mucin. Only mouse mammary tumor virus (from C(3)H or Paris RIII strains and grown in either murine or feline cells) and purified gp52 eliminated the immunohistochemical reaction in the human breast tumors. Positive reactions were seen in 51 of 131 (39%) breast carcinomas of various histologic types, a minimal estimate in view of the limited number of sections from each tumor that could be examined. Negative reactions were obtained in all 119 benign breast lesions (cystic disease, fibroadenoma, papilloma, gynecomastia) and in all 18 normal breast tissues. With one exception, 99 carcinomas from 13 organs other than breast and 8 cystosarcomas were all negative.

  8. Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland.

    Science.gov (United States)

    Annunziato, Stefano; Kas, Sjors M; Nethe, Micha; Yücel, Hatice; Del Bravo, Jessica; Pritchard, Colin; Bin Ali, Rahmen; van Gerwen, Bas; Siteur, Bjørn; Drenth, Anne Paulien; Schut, Eva; van de Ven, Marieke; Boelens, Mirjam C; Klarenbeek, Sjoerd; Huijbers, Ivo J; van Miltenburg, Martine H; Jonkers, Jos

    2016-06-15

    Large-scale sequencing studies are rapidly identifying putative oncogenic mutations in human tumors. However, discrimination between passenger and driver events in tumorigenesis remains challenging and requires in vivo validation studies in reliable animal models of human cancer. In this study, we describe a novel strategy for in vivo validation of candidate tumor suppressors implicated in invasive lobular breast carcinoma (ILC), which is hallmarked by loss of the cell-cell adhesion molecule E-cadherin. We describe an approach to model ILC by intraductal injection of lentiviral vectors encoding Cre recombinase, the CRISPR/Cas9 system, or both in female mice carrying conditional alleles of the Cdh1 gene, encoding for E-cadherin. Using this approach, we were able to target ILC-initiating cells and induce specific gene disruption of Pten by CRISPR/Cas9-mediated somatic gene editing. Whereas intraductal injection of Cas9-encoding lentiviruses induced Cas9-specific immune responses and development of tumors that did not resemble ILC, lentiviral delivery of a Pten targeting single-guide RNA (sgRNA) in mice with mammary gland-specific loss of E-cadherin and expression of Cas9 efficiently induced ILC development. This versatile platform can be used for rapid in vivo testing of putative tumor suppressor genes implicated in ILC, providing new opportunities for modeling invasive lobular breast carcinoma in mice. © 2016 Annunziato et al.; Published by Cold Spring Harbor Laboratory Press.

  9. Papillary-cystic pattern is characteristic in mammary analogue secretory carcinomas but is rarely observed in acinic cell carcinomas of the salivary gland.

    Science.gov (United States)

    Hsieh, Min-Shu; Chou, Yueh-Hung; Yeh, Shin-Joe; Chang, Yih-Leong

    2015-08-01

    Mammary analogue secretory carcinoma (MASC) has a specific ETV6-NTRK3 translocation and morphologically overlaps with acinic cell carcinoma (AciCC). Before the recognition of MASC, in AciCC, four histologic patterns were identified including microcystic, solid, papillary-cystic, and follicular. The aim of this study was to evaluate histologic patterns in these two neoplasms through comprehensive histologic subtyping. Using fluorescence in situ hybridization (FISH), we identified 14 cases of MASC and 21 cases of AciCC. We used comprehensive histologic subtyping to provide a semiquantitive assessment of histologic patterns in each tumor and performed immunohistochemical analyses including S100/vimentin/mammaglobin/DOG1. MASC often presented papillary-cystic patterns without a solid component, previously considered to be one of the four major patterns associated with AciCC. However, in our study, this histologic feature was rarely seen in AciCC and more characteristic of MASC. In aspiration cytology samples, MASC was associated with more cellular atypia. An immunohistochemical panel of S100/mammaglobin/DOG1 was found useful for differential diagnosis. Comprehensive subtyping of histologic patterns is a useful screening method prior to initiation of molecular testing.

  10. Effects of dietary gamma-linolenic acid and docosahexaenoic acid with paclitaxel on the treatment of mice mammary carcinoma

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    Kamran Rakhshan

    2013-08-01

    Full Text Available Background: Breast cancer is one of the most important causes of death in women. One of the various gene expression involved in breast cancer is human epidermal growth factor receptor 2 (HER2/neu gene expression increases. Factors of dietary affect on regulation of hormone secretion and the rate of breast cancer. One of these factors is amount and type of fats in diet. Gamma-linolenic acid (GLA and Docosah-exaenoic acid (DHA are members of poly unsaturated fatty acids. In this study, effects of dietary GLA and DHA alone or together with paclitaxel on treatment of mice mammary carcinoma has been evaluated.Methods: Thirty female balb/c mice were divided in six groups randomly. Carcinoma-tous mass induced by tumor implantation method. Spontaneous breast adenocarcinoma of mice were used as tumor stock. The tumors of these mice were removed aseptically, dissected into 0.5 cm3 pieces. These pieces were transplanted subcutaneously into their right flank. GLA and DHA added to the mice diet two week prior to tumor implanta-tion. At the end of intervention, tumors were removed and HER2 gene expression was measured. The weight of animal and tumor volume measured weekly.Results: It was not significant change in the weight of animals that consumed DHA and DHA with taxol. Tumor volume in those groups that received corn oil with taxol (P<0.01, DHA (P<0.05 and DHA with taxol (P<0.001 showed significant decrease in comparison with control group. HER2 gene expression in DHA with taxol decreased significantly in comparison with control group (P<0.05.Conclusion: Consumption of DHA oil with taxol causes decrease the volume of carcin-oma mass. The future studies with large number of sample is needed to support this finding.

  11. Therapeutic effect of Semecarpus anacardium Linn. nut milk extract on carbohydrate metabolizing and mitochondrial TCA cycle and respiratory chain enzymes in mammary carcinoma rats.

    Science.gov (United States)

    Arathi, G; Sachdanandam, P

    2003-09-01

    Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. We have evaluated the effect of S. anacardium nut milk extract on carbohydrate metabolizing enzymes and mitochondrial tricarboxylic acid cycle and respiratory enzymes in liver and kidney mitochondria of dimethyl benzanthracene-induced mammary carcinoma in Sprague-Dawley rats. Mammary carcinoma-bearing rats showed a significant rise in glycolytic enzymes (hexokinase, phosphoglucoisomerase and aldolase) and a simultaneous fall in gluconeogenic enzymes (glucose-6-phosphatase and fructose 1,6-diphosphatase). The activities of mitochondrial enzymes isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH-dehydrogenase and cytochrome C oxidase were significantly lowered in mammary carcinoma-bearing rats when compared with control rats. S. anacardium nut extract administration to tumour-induced animals significantly lowered the glycolytic enzyme activities (hexokinase, phosphoglucoisomerase and aldolase) and there was a rise in gluconeogenic enzymes (glucose-6-phosphatase and fructose 1,6-diphosphatase), which indicated an antitumour and anticancer effect. Comparison of normal control rats and rats administered S. anacardium only as drug control animals showed no significant variations in enzyme activities. S. anacardium nut extract administration to dimethyl benzanthracene-tumour-induced animals significantly increased the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.

  12. Truncating Prolactin Receptor Mutations Promote Tumor Growth in Murine Estrogen Receptor-Alpha Mammary Carcinomas

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    Obi L. Griffith

    2016-09-01

    Full Text Available Estrogen receptor alpha-positive (ERα+ luminal tumors are the most frequent subtype of breast cancer. Stat1−/− mice develop mammary tumors that closely recapitulate the biological characteristics of this cancer subtype. To identify transforming events that contribute to tumorigenesis, we performed whole genome sequencing of Stat1−/− primary mammary tumors and matched normal tissues. This investigation identified somatic truncating mutations affecting the prolactin receptor (PRLR in all tumor and no normal samples. Targeted sequencing confirmed the presence of these mutations in precancerous lesions, indicating that this is an early event in tumorigenesis. Functional evaluation of these heterozygous mutations in Stat1−/− mouse embryonic fibroblasts showed that co-expression of truncated and wild-type PRLR led to aberrant STAT3 and STAT5 activation downstream of the receptor, cellular transformation in vitro, and tumor formation in vivo. In conclusion, truncating mutations of PRLR promote tumor growth in a model of human ERα+ breast cancer and warrant further investigation.

  13. Truncating Prolactin Receptor Mutations Promote Tumor Growth in Murine Estrogen Receptor-Alpha Mammary Carcinomas.

    Science.gov (United States)

    Griffith, Obi L; Chan, Szeman Ruby; Griffith, Malachi; Krysiak, Kilannin; Skidmore, Zachary L; Hundal, Jasreet; Allen, Julie A; Arthur, Cora D; Runci, Daniele; Bugatti, Mattia; Miceli, Alexander P; Schmidt, Heather; Trani, Lee; Kanchi, Krishna-Latha; Miller, Christopher A; Larson, David E; Fulton, Robert S; Vermi, William; Wilson, Richard K; Schreiber, Robert D; Mardis, Elaine R

    2016-09-27

    Estrogen receptor alpha-positive (ERα+) luminal tumors are the most frequent subtype of breast cancer. Stat1(-/-) mice develop mammary tumors that closely recapitulate the biological characteristics of this cancer subtype. To identify transforming events that contribute to tumorigenesis, we performed whole genome sequencing of Stat1(-/-) primary mammary tumors and matched normal tissues. This investigation identified somatic truncating mutations affecting the prolactin receptor (PRLR) in all tumor and no normal samples. Targeted sequencing confirmed the presence of these mutations in precancerous lesions, indicating that this is an early event in tumorigenesis. Functional evaluation of these heterozygous mutations in Stat1(-/-) mouse embryonic fibroblasts showed that co-expression of truncated and wild-type PRLR led to aberrant STAT3 and STAT5 activation downstream of the receptor, cellular transformation in vitro, and tumor formation in vivo. In conclusion, truncating mutations of PRLR promote tumor growth in a model of human ERα+ breast cancer and warrant further investigation. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Evaluation of Bone Cancer Pain Induced by Different Doses of Walker 256 Mammary Gland Carcinoma Cells.

    Science.gov (United States)

    Dong, Changsheng; Wu, RuiXin; Wu, Jing; Guo, Jing; Wang, Fangyuan; Fu, Yanli; Wang, Qing; Xu, Ling; Wang, Juyong

    2016-01-01

    Cancer pain is a complex medical syndrome. Understanding its underlying mechanisms relies on the use of animal models which can mimic the human condition. A crucial component of this model is the quantity of tumor cells; however, the exact relationship between the doses of tumor cells on bone cancer pain is yet unknown. We explored the relationship of different doses of Walker 256 carcinoma cells using a bone cancer pain model in rats, and evaluated its success and stability. Experimental animal study using a comparative design. Experimental Animal Center and Tumor Institute of Traditional Chinese Medicine. We constructed the bone cancer pain model by implanting Walker 256 carcinoma cells into the right tibia of Sprague-Dawley (SD) rats (150 - 170 g). Spontaneous pain, mechanical threshold, and paw withdrawal latency (PWL) were measured and x-ray, bone mineral density (BMD), histological, interleukin-1 beta (IL-1beta) mRNA, carboxyterminal telopeptide of type I collagen (ICTP), and bone alkaline phosphatase (BAP) were analyzed for bone pain model evaluation. The results showed that: (1) the 3 doses (3×105, 3.5×105, 4×105) of Walker 256 carcinoma cells can induce bone cancer pain from day 7 to day 21 after implantation into the right tibia of SD rats; (2) compared to the control group, 3×105, 3.5×105, and 4×105 Walker 256 carcinoma cells produced different pain manifestations, where the 3.5×105 dose of Walker 256 carcinoma cells resulted in the greatest bone cancer pain response; (3) the 3.5×105 dose induced the lowest mortality rate in rats; (4) Walker 256 carcinoma cells (3×105, 3.5×105, and 4×105) resulted in a significant decrease in the general condition and body weight of rats, where the 3.5×105 and 4×105 doses of carcinoma cells produced a greater effect than 3×105 dose of carcinoma cells; (5) progressive spontaneous pain, PWL, and mechanical threshold were exacerbated by 3.5×105 and 4×105 doses of carcinoma cells; (6) implantation of 3.5×105

  15. Co-cultivation of murine BMDCs with 67NR mouse mammary carcinoma cells give rise to highly drug resistant cells

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    Zänker Kurt S

    2011-06-01

    Full Text Available Abstract Background Tumor tissue resembles chronically inflamed tissue. Since chronic inflammatory conditions are a strong stimulus for bone marrow-derived cells (BMDCs it can be assumed that recruitment of BMDCs into cancer tissue should be a common phenomenon. Several data have outlined that BMDC can influence tumor growth and metastasis, e.g., by inducing a paracrine acting feedback loop in tumor cells. Likewise, cell fusion and horizontal gene transfer are further mechanisms how BMDCs can trigger tumor progression. Results Hygromycin resistant murine 67NR-Hyg mammary carcinoma cells were co-cultivated with puromycin resistant murine BMDCs from Tg(GFPU5Nagy/J mice. Isolation of hygromycin/puromycin resistant mBMDC/67NR-Hyg cell clones was performed by a dual drug selection procedure. PCR analysis revealed an overlap of parental markers in mBMDC/67NR-Hyg cell clones, suggesting that dual resistant cells originated by cell fusion. By contrast, both STR and SNP data analysis indicated that only parental 67NR-Hyg alleles were found in mBMDC/67NR-Hyg cell clones favoring horizontal gene transfer as the mode of origin. RealTime-PCR-array analysis showed a marked up-regulation of Abcb1a and Abcb1b ABC multidrug transporters in mBMDC/67NR-Hyg clones, which was verified by Western Blot analysis. Moreover, the markedly increased Abcb1a/Abcb1b expression was correlated to an efficient Rhodamine 123 efflux, which was completely inhibited by verapamil, a well-known Abcb1a/Abcb1b inhibitor. Likewise, mBMDCs/67NR-Hyg clones revealed a marked resistance towards chemotherapeutic drugs including 17-DMAG, doxorubicin, etoposide and paclitaxel. In accordance to Rhodamine 123 efflux data, chemotherapeutic drug resistance of mBMDC/67NR-Hyg cells was impaired by verapamil mediated blockage of Abc1a/Abcb1b multidrug transporter function. Conclusion Co-cultivation of mBMDCs and mouse 67NR-Hyg mammary carcinoma cells gave rise to highly drug resistant cells. Even

  16. Inhibitory and Apoptosis-Inducing Effects of Newcastle Disease Virus Strain AF2240 on Mammary Carcinoma Cell Line

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    Umar Ahmad

    2015-01-01

    Full Text Available Breast cancer is the malignant tumour that developed from cells of the breast and is the first leading cause of cancer death among women worldwide. Surgery, radiotherapy, and chemotherapy are the available treatments for breast cancer, but these were reported to have side effects. Newcastle disease virus (NDV known as Avian paramyxovirus type-1 (APMV1 belongs to the genus Avulavirus in a family Paramyxoviridae. NDV is shown to be a promising anticancer agent, killing tumour cells while sparing normal cells unharmed. In this study, the oncolytic and cytotoxic activities of NDV AF2240 strain were evaluated on MDA-MB-231, human mammary carcinoma cell line, using MTT assay, and its inhibitory effects were further studied using proliferation and migration assays. Morphological and apoptotic-inducing effects of NDV on MD-MB-231 cells were observed using phase contrast and fluorescence microscopes. Detection of DNA fragmentation was done following terminal deoxyribonucleotide transferase-mediated Br-dUTP nick end labeling staining (TUNEL assay, which confirmed that the mode of death was through apoptosis and was quantified by flow cytometry. Furthermore, analysis of cellular DNA content demonstrated that the virus caused an increase in the sub-G1 phase (apoptotic peak of the cell cycle. It appears that NDV AF2240 strain is a potent anticancer agent that induced apoptosis in time-dependent manner.

  17. Extracts of red yolk from duck eggs inhibit metastasis of human mammary carcinoma (4T1 cells in mice

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    Song Qi-bin

    2011-06-01

    Full Text Available The aim of the present study was to investigate the in vivo anti-metastatic activity of the red pigments of red yolk eggs laid by the ducks dieting on Potamogeton cripus L on the mammary carcinoma (4T1. The pigments were extracted with petroleum ether and acetone (2:1, v/v. BALB/c mice were divided into three groups (n=6, fed with the extracts at 150 mg/kg body weight (BW/day (DEYE-H or at 50 mg/kg BW/day (DEYE-L and identical buffer without the extract (control group. The extracts were administered for 34 days. The treatment significantly inhibited the growth of orthotopical 4T1 tumour (DEYE-H vs control, 1:2; DEYE-L vs control, 2:3 and reduced the metastasis of tumour in the lungs (DEYE-H vs control, 4:7; DEYE-L vs control, 5:7, without statistical difference of body weight among the three groups.

  18. Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

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    Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J

    1998-06-29

    Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

  19. Mammary Analogue Secretory Carcinoma Presenting as a Cervical Lymph Node Metastasis of Unknown Primary Site: A Case Report.

    Science.gov (United States)

    Suzuki, Kensuke; Yagi, Masao; Kanda, Akira; Kobayashi, Yoshiki; Konishi, Masaya; Miyasaka, Chika; Tashiro, Takashi; Iwai, Hiroshi

    2017-01-01

    Mammary analogue secretory carcinoma (MASC) is a pathological entity arising in the salivary glands first described by Skalova et al. [Am J Surg Pathol 2010;34: 599-608]. Here, we report the first case of MASC presenting as a cervical lymph node metastasis of unknown primary site together with a brief review of the literature. We present a 74-year-old male with a painless lump in his left neck. Based on the fine-needle aspiration cytological findings, a possible malignant tumor was suspected. No evidence of a primary lesion was observed using imaging modalities including positron emission tomography/computed tomography. The patient underwent an ipsilateral modified radical neck dissection. Immunohistochemical staining showed that the neoplastic cells were positive for S100 protein and GATA3. A rearrangement of the ETV6 gene was noted during fluorescence in situ hybridization, and the final histopathological diagnosis was MASC. We encountered a MASC presenting as a cervical lymph node metastasis of unknown primary site. No adjuvant therapy was administered, and no local recurrence or metastatic disease has been detected during a follow-up period of 9 months. This is the first case report of MASC presenting as a cervical lymph node metastasis of unknown primary site and suggests the new properties of MASC.

  20. Mammary Analogue Secretory Carcinoma Presenting as a Cervical Lymph Node Metastasis of Unknown Primary Site: A Case Report

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    Kensuke Suzuki

    2017-02-01

    Full Text Available Background: Mammary analogue secretory carcinoma (MASC is a pathological entity arising in the salivary glands first described by Skalova et al. [Am J Surg Pathol 2010;34: 599–608]. Here, we report the first case of MASC presenting as a cervical lymph node metastasis of unknown primary site together with a brief review of the literature. Case Report: We present a 74-year-old male with a painless lump in his left neck. Based on the fine-needle aspiration cytological findings, a possible malignant tumor was suspected. No evidence of a primary lesion was observed using imaging modalities including positron emission tomography/computed tomography. The patient underwent an ipsilateral modified radical neck dissection. Immunohistochemical staining showed that the neoplastic cells were positive for S100 protein and GATA3. A rearrangement of the ETV6 gene was noted during fluorescence in situ hybridization, and the final histopathological diagnosis was MASC. Conclusion: We encountered a MASC presenting as a cervical lymph node metastasis of unknown primary site. No adjuvant therapy was administered, and no local recurrence or metastatic disease has been detected during a follow-up period of 9 months. This is the first case report of MASC presenting as a cervical lymph node metastasis of unknown primary site and suggests the new properties of MASC.

  1. Molecular analysis of a mammary analog secretory carcinoma in the upper lip

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    Masanobu Abe

    2015-01-01

    Conclusion: We experienced a rare malignant salivary gland carcinoma, MASC. We diagnosed this tumor by molecular approach and subsequently tried to identify novel molecular abnormalities. Although no novel molecular alteration except for EN fusion gene was identified, this result might represent the favorable prognosis of patients with MASC.

  2. Modulatory effect of Pleurotus ostreatus on oxidant/antioxidant status in 7, 12-dimethylbenz (a) anthracene induced mammary carcinoma in experimental rats--A dose-response study.

    Science.gov (United States)

    Krishnamoorthy, Deepalakshmi; Sankaran, Mirunalini

    2016-01-01

    Worldwide, breast cancer is the second most prevalent cancer among women and its incidence is increasing alarmingly. To determine a dose-response effect of Pleurotus ostreatus on oxidant/antioxidant status in 7,12-dimethylbenz. (a) antheracene induced. (DMBA) mammary carcinoma in experimental rats. Cancer bearing female Sprague Dawley rats were orally treated with Pleurotus ostreatus ethanolic extract (POEet) (150, 300 and 600 mg/kg body weight) for 16 weeks. By means of high performance liquid chromatography (HPLC) analysis, ergosterol (48.82%) were identified and quantified in POEet. Body weight of experimental rats in each groups and the biochemical parameters of plasma, liver and mammary tissues were carried out. Histopathological analyses were also determined. Results were analyzed using SPSS software package, version 16.0. The values were analyzed by one way analysis of variance (ANOVA) followed by Duncan's multiple range test (DMRT). The result showed that depleted activities of enzymatic and non-enzymatic antioxidant level and significant elevated TBARS level were observed in DMBA group of plasma, mammary and liver tissues of experimental rats. The effects were dose.dependent and the above noted parameters were renovated to near normal after supplementation with different dose of POEet (150 mg, 300 mg and 600 mg/kg bwt). The data obtained from the study indicate that POEet at a dose of 600 mg/kg bwt possesses optimum anticancer effects against DMBA induced mammary carcinogenesis. Based on the scientific appraisal, we conclude that the POEet is having a potent antioxidant capacity; thereby it offers maximum protection against DMBA-induced mammary carcinogenesis.

  3. Metformin augments doxorubicin cytotoxicity in mammary carcinoma through activation of adenosine monophosphate protein kinase pathway.

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    El-Ashmawy, Nahla E; Khedr, Naglaa F; El-Bahrawy, Hoda A; Abo Mansour, Hend E

    2017-05-01

    Since the incidence of breast cancer increases dramatically all over the world, the search for effective treatment is an urgent need. Metformin has demonstrated anti-tumorigenic effect both in vivo and in vitro in different cancer types. This work was designed to examine on molecular level the mode of action of metformin in mice bearing solid Ehrlich carcinoma and to evaluate the use of metformin in conjunction with doxorubicin as a combined therapy against solid Ehrlich carcinoma. Ehrlich ascites carcinoma cells were inoculated in 60 female mice as a model of breast cancer. The mice were divided into four equal groups: Control tumor, metformin, doxorubicin, and co-treatment. Metformin (15 mg/kg) and doxorubicin (4 mg/kg) were given intraperitoneally (i.p.) for four cycles every 5 days starting on day 12 of inoculation. The anti-tumorigenic effect of metformin was mediated by enhancement of adenosine monophosphate protein kinase activity and elevation of P53 protein as well as the suppression of nuclear factor-kappa B, DNA contents, and cyclin D1 gene expression. Metformin and doxorubicin mono-treatments exhibited opposing action regarding cyclin D1 gene expression, phosphorylated adenosine monophosphate protein kinase, and nuclear factor-kappa B levels. Co-treatment markedly decreased tumor volume, increased survival rate, and improved other parameters compared to doxorubicin group. In parallel, the histopathological findings demonstrated enhanced apoptosis and absence of necrosis in tumor tissue of co-treatment group. Metformin proved chemotherapeutic effect which could be mediated by the activation of adenosine monophosphate protein kinase and related pathways. Combining metformin and doxorubicin, which exhibited different mechanisms of action, produced greater efficacy as anticancer therapeutic regimen.

  4. Absence of significant adverse events following thalidomide administration in bitches diagnosed with mammary gland carcinomas.

    Science.gov (United States)

    de Campos, C B; Lavalle, G E; Fialho Ligório, S; Camargo Nunes, F; Carneiro, R A; Amorim, R L; Cassali, G D

    2016-11-19

    The aim of the study was to evaluate the incidence of adverse events (AEs) in female dogs diagnosed with advanced clinical stage mammary gland neoplasms following treatment with thalidomide. A prospective analysis of 29 female dogs treated with a high dose (HD) of 20 mg/kg/day of thalidomide for three months followed by a low dose (LD) of 10 mg/kg/day of thalidomide for three months was performed. All patients underwent physical examination, complete blood count, serum biochemistry profile, thoracic radiographs, and abdominal ultrasound analysis before the treatment and after the HD and LD. Clinical AEs were absent in 16/29 (55.17 per cent) patients following HD. An initial 3-5 day period of somnolence was described in 4/29 (13.79 per cent), prolonged somnolence in 5/29 (17.24 per cent), a short period of somnolence lasting only a few hours in 3/29 (10.34 per cent), and difficulty to rouse was described in 5/29 (17.24 per cent) cases. Two patients (6.89 per cent) presented with prolonged somnolence that interfered with activities of daily living, resulting in anticipation of the dose reduction to the proposed LD after 15 days of the HD treatment. Following dose reduction, AE improvement was observed in all patients. Albeit remaining within the reference ranges, erythrocytes, haematocrit, total leucocyte count, neutrophils, lymphocytes, monocytes and γ-glutamyltranspeptidase showed significant alteration associated to thalidomide treatment. British Veterinary Association.

  5. Cytological features of mammary analogue secretory carcinoma of salivary gland: fine-needle aspiration of seven cases.

    Science.gov (United States)

    Higuchi, Kayoko; Urano, Makoto; Takahashi, Reisuke H; Oshiro, Hisashi; Matsubayashi, Jun; Nagai, Takeshi; Obikane, Hiyo; Shimojo, Hisashi; Nagao, Toshitaka

    2014-10-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is defined by ETV6-NTRK3 gene fusion. There have been few case reports on the cytopathologic features of MASC to date. We examined the clinicopathological and cytological features of seven cases of MASC defined by RT-PCR analysis of the ETV6-NTRK3 fusion gene. The cases occurred in three men and four women aged between 39 and 68 years, with a mean of 51.6 years. In five of these seven cases, the tumor involved the parotid gland. Histologically, all cases displayed predominantly microcystic patterns, often a mixture of follicular and papillary-cystic structures. All tumors were immunoreactive for mammaglobin, S-100 protein, and vimentin. Available fine-needle aspiration cytology smears were cellular and exhibited many loosely cohesive syncytial clusters or isolated cells. Many histiocytes, some of which contained hemosiderin pigments, and variously shaped mucinous material were evident in the background or within the epithelial clusters. The majority of cases showed small to medium-sized follicular structures with secreted materials. Papillary clusters were occasionally found. Tumor cells exhibited small to medium-sized round to oval nuclei, with a smooth contour and indistinct or small nucleoli, and vacuolated cytoplasm. No tumor cells had obvious intracytoplasmic zymogen granules. It appeared that clusters of small to medium-sized follicular and papillary configurations consisting of bland tumor cells with vacuolated cytoplasm, but lack of intracytoplasmic zymogen granules, in a mucinous or hemosiderin-laden histiocyte-rich background, were a characteristic cytological feature highly suggestive of MASC. © 2014 Wiley Periodicals, Inc.

  6. Cytological Features of Mammary Analogue Secretory Carcinoma of the Parotid Gland in a 15-Year-Old Girl: A Case Report with Review of the Literature

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    Takako Inaba

    2015-01-01

    Full Text Available Mammary analogue secretory carcinoma (MASC is a recently recognized tumor of salivary glands characterized by the ETV6-NTRK3 fusion gene. This tumor is very rare in children and adolescents. We report a case of MASC in a 15-year-old girl, the fifth youngest case so far reported. The patient complained of a left infra-auricular mass that gradually enlarged for a year. Fine-needle aspiration cytology/imprint cytology showed individual tumor cells that had faintly eosinophilic granular cytoplasm with secretion granules sometimes seen adjacent to the tumor cells. These cytological features overlapped between those of zymogen granule-poor acinic cell carcinoma (AciCC and MASC. In addition to the case report, we present a review of the related literature with a focus on the cytological features of MASC. The differential diagnostic clues are also discussed.

  7. Cytological features of mammary analogue secretory carcinoma of the parotid gland in a 15-year-old girl: a case report with review of the literature.

    Science.gov (United States)

    Inaba, Takako; Fukumura, Yuki; Saito, Tsuyoshi; Yokoyama, Junkichi; Ohba, Shinichi; Arakawa, Atsushi; Yao, Takashi

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) is a recently recognized tumor of salivary glands characterized by the ETV6-NTRK3 fusion gene. This tumor is very rare in children and adolescents. We report a case of MASC in a 15-year-old girl, the fifth youngest case so far reported. The patient complained of a left infra-auricular mass that gradually enlarged for a year. Fine-needle aspiration cytology/imprint cytology showed individual tumor cells that had faintly eosinophilic granular cytoplasm with secretion granules sometimes seen adjacent to the tumor cells. These cytological features overlapped between those of zymogen granule-poor acinic cell carcinoma (AciCC) and MASC. In addition to the case report, we present a review of the related literature with a focus on the cytological features of MASC. The differential diagnostic clues are also discussed.

  8. Identifying three different architectural subtypes of mammary ductal carcinoma in situ using multiphoton microscopy

    Science.gov (United States)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, shuangmu; Wang, Chuan; Chen, Jianxin

    2015-10-01

    Ductal carcinoma in situ (DCIS) is often considered as the precursor of invasive breast cancer, and the risk of DCIS progression to IBC has been estimated based on the evaluation of pathological features, among which the architectural subtype is the most common one. In this study, multiphoton microscopy (MPM) is applied to identify three different architectural subtypes of DCIS (solid, cribriform and comedo). It is found that MPM has the capability to visualize the proliferating pattern of tumor cells, the presence of intraluminal necrosis and the morphology of basement membrane, which are all taken into account in subtyping DCIS. In addition, MPM also can be used to quantify the cellular metabolism, for quantitatively identifying tumor staging during tumor progression. This result highlights the potential of MPM as an advanced technique to assess the pathological characters of the breast tumor in real-time and reflect the degree of tumor progression in vivo, by integrating into the intra-fiberoptic ductoscopy or transdermal biopsy needle.

  9. Danish randomized trial comparing breast-preserving therapy with mastectomy in mammary carcinoma. Preliminary results

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    Blichert-Toft, M.; Brincker, H.; Andersen, J.A.; Andersen, K.W.; Axelsson, C.K.; Mouridsen, H.T.; Dombernowsky, P.; Overgaard, M.; Gadeberg, C.; Knudsen, G.

    1988-01-01

    The present study comprises 847 women operated upon for invasive breast carcinoma at 19 surgical departments and enrolled in protocol DBCG-82TM from January 1983 to November 1987. Among them 662 (78%) were allocated for breast-preserving therapy or mastectomy by randomization, while 185 patients (22%) did not accept randomization. Within the randomized group 6% could not be entered into adjuvant protocols, i.e. subsequent programmes of postoperative therapy and follow-up. This left 619 evaluable patients. In the non-randomized series 26% did not fulfil the demands for entrance into the adjuvant protocols, leaving 136 evaluable patients, 60 of whom had chosen a breast-preserving operation and 76 mastectomy. In the randomized series the patients in the two treatment arms were comparable in age, menopausal status, site of tumour, pathoanatomical diameter of the tumour, number of removed axillary lymph nodes, number of metastatic axillary lymph nodes, and distribution on adjuvant regimens. Ninety per cent of the patients in the randomized group accepted the method offered, whereas 10% declined and wanted the alternate form of operation. The median follow-up period was approximately 1.75 years. The cumulative recurrence rate in the randomized group was 13% and in the non-randomized group 7%. These results are preliminary. Life-table analyses have not so far demonstrated differences in recurrence-free survival either in the randomized or the non-randomized series.

  10. Different gene-expression profiles for the poorly differentiated carcinoma and the highly differentiated papillary adenocarcinoma in mammary glands support distinct metabolic pathways

    Directory of Open Access Journals (Sweden)

    Barash Itamar

    2008-09-01

    Full Text Available Abstract Background Deregulation of Stat5 in the mammary gland of transgenic mice causes tumorigenesis. Poorly differentiated carcinoma and highly differentiated papillary adenocarcinoma tumors evolve. To distinguish the genes and elucidate the cellular processes and metabolic pathways utilized to preserve these phenotypes, gene-expression profiles were analyzed. Methods Mammary tumors were excised from transgenic mice carrying a constitutively active variant of Stat5, or a Stat5 variant lacking s transactivation domain. These tumors displayed either the carcinoma or the papillary adenocarcinoma phenotypes. cRNAs, prepared from each tumor were hybridized to an Affymetrix GeneChip® Mouse Genome 430A 2.0 array. Gene-ontology analysis, hierarchical clustering and biological-pathway analysis were performed to distinct the two types of tumors. Histopathology and immunofluorescence staining complemented the comparison between the tumor phenotypes. Results The nucleus-cytoskeleton-plasma membrane axis is a major target for differential gene expression between phenotypes. In the carcinoma, stronger expression of genes coding for specific integrins, cytoskeletal proteins and calcium-binding proteins highlight cell-adhesion and motility features of the tumor cells. This is supported by the higher expression of genes involved in O-glycan synthesis, TGF-β, activin, their receptors and Smad3, as well as the Notch ligands and members of the γ-secretase complex that enable Notch nuclear localization. The Wnt pathway was also a target for differential gene expression. Higher expression of genes encoding the degradation complex of the canonical pathway and limited TCF expression in the papillary adenocarcinoma result in membranal accumulation of β-catenin, in contrast to its nuclear translocation in the carcinoma. Genes involved in cell-cycle arrest at G1 and response to DNA damage were more highly expressed in the papillary adenocarcinomas, as opposed to

  11. Aspiration biopsy of mammary analogue secretory carcinoma of accessory parotid gland: another diagnostic dilemma in matrix-containing tumors of the salivary glands.

    Science.gov (United States)

    Levine, Pascale; Fried, Karen; Krevitt, Lane D; Wang, Beverly; Wenig, Bruce M

    2014-01-01

    Mammary analogue secretory carcinoma (MASC) is a newly described rare salivary gland tumor, which shares morphologic features with acinic cell carcinoma, low-grade cystadenocarcinoma, and secretory carcinoma of the breast. This is the first reported case of MASC of an accessory parotid gland detected by aspiration biopsy with radiologic and histologic correlation in a 34-year-old patient. Sonographically-guided aspiration biopsy showed cytologic features mimicking those of low-grade mucoepidermoid carcinoma, including sheets of bland epithelial cells, dissociated histiocytoid cells with intracytoplasmic mucinous material, and spindle cells lying in a web-like matrix. Histologic sections showed a circumscribed tumor with microcystic spaces lined by bland uniform epithelial cells and containing secretory material. The tumor cells expressed mammaglobin and BRST-2. The cytologic features, differential diagnosis, and pitfalls are discussed. The pathologic stage was pT1N0. The patient showed no evidence of disease at 1 year follow-up. Copyright © 2012 Wiley Periodicals, Inc.

  12. Live-Cell Imaging Visualizes Frequent Mitotic Skipping During Senescence-Like Growth Arrest in Mammary Carcinoma Cells Exposed to Ionizing Radiation

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    Suzuki, Masatoshi, E-mail: msuzuki@nagasaki-u.ac.jp [Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan); Yamauchi, Motohiro; Oka, Yasuyoshi; Suzuki, Keiji; Yamashita, Shunichi [Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (Japan)

    2012-06-01

    Purpose: Senescence-like growth arrest in human solid carcinomas is now recognized as the major outcome of radiotherapy. This study was designed to analyze cell cycle during the process of senescence-like growth arrest in mammary carcinoma cells exposed to X-rays. Methods and Materials: Fluorescent ubiquitination-based cell cycle indicators were introduced into the human mammary carcinoma cell line MCF-7. Cell cycle was sequentially monitored by live-cell imaging for up to 5 days after exposure to 10 Gy of X-rays. Results: Live-cell imaging revealed that cell cycle transition from G2 to G1 phase without mitosis, so-called mitotic skipping, was observed in 17.1% and 69.8% of G1- and G2-irradiated cells, respectively. Entry to G1 phase was confirmed by the nuclear accumulation of mKO{sub 2}-hCdt1 as well as cyclin E, which was inversely correlated to the accumulation of G2-specific markers such as mAG-hGeminin and CENP-F. More than 90% of cells skipping mitosis were persistently arrested in G1 phase and showed positive staining for the senescent biochemical marker, which is senescence-associated ss-galactosidase, indicating induction of senescence-like growth arrest accompanied by mitotic skipping. While G2 irradiation with higher doses of X-rays induced mitotic skipping in approximately 80% of cells, transduction of short hairpin RNA (shRNA) for p53 significantly suppressed mitotic skipping, suggesting that ionizing radiation-induced mitotic skipping is associated with p53 function. Conclusions: The present study found the pathway of senescence-like growth arrest in G1 phase without mitotic entry following G2-irradiation.

  13. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity.

    Science.gov (United States)

    Skálová, Alena; Vanecek, Tomas; Sima, Radek; Laco, Jan; Weinreb, Ilan; Perez-Ordonez, Bayardo; Starek, Ivo; Geierova, Marie; Simpson, Roderrick H W; Passador-Santos, Fabricio; Ryska, Ales; Leivo, Ilmo; Kinkor, Zdenek; Michal, Michal

    2010-05-01

    We present a series of 16 salivary gland tumors with histomorphologic and immunohistochemical features reminiscent of secretory carcinoma of the breast. This is a hitherto undescribed and distinctive salivary gland neoplasm, with features resembling both salivary acinic cell carcinoma (AciCC) and low-grade cystadenocarcinoma, and displaying strong similarities to breast secretory carcinoma. Microscopically, the tumors have a lobulated growth pattern and are composed of microcystic and glandular spaces with abundant eosinophilic homogenous or bubbly secretory material positive for periodic acid-Schiff, mucicarmine, MUC1, MUC4, and mammaglobin. The neoplasms also show strong vimentin, S-100 protein, and STAT5a positivity. For this tumor, we propose a designation mammary analogue secretory carcinoma of salivary glands (MASC). The 16 patients comprised 9 men and 7 women, with a mean age of 46 years (range 21 to 75). Thirteen cases occurred in the parotid gland, and one each in the minor salivary glands of the buccal mucosa, upper lip, and palate. The mean size of the tumors was 2.1 cm (range 0.7 to 5.5 cm). The duration of symptoms was recorded in 11 cases and ranged from 2 months to 30 years. Clinical follow-up was available in 13 cases, and ranged from 3 months to 10 years. Four patients suffered local recurrences. Two patients died, 1 of them owing to multiple local recurrences with extension to the temporal bone, and another owing to metastatic dissemination to cervical lymph nodes, pleura, pericardium, and lungs. We have shown a t(12;15) (p13;q25) ETV6-NTRK3 translocation in all but one case of MASC suitable for analysis. One case was not analyzable and another was not available for testing. This translocation was not found in any conventional salivary AciCC (12 cases), nor in other tumor types including pleomorphic adenoma (1 case) and low-grade cribriform cystadenocarcinoma (1 case), whereas ETV6-NTRK3 gene rearrangements were proven in all 3 tested cases of

  14. Characterization of mammary analogue secretory carcinoma of the salivary gland: discrimination from its mimics by the presence of the ETV6-NTRK3 translocation and novel surrogate markers.

    Science.gov (United States)

    Urano, Makoto; Nagao, Toshitaka; Miyabe, Satoru; Ishibashi, Kenichiro; Higuchi, Kayoko; Kuroda, Makoto

    2015-01-01

    Mammary analogue secretory carcinoma (MASC) is a recently recognized salivary gland tumor harboring an ETV6-NTRK3 translocation similar to secretory carcinoma of the breast. Histologically, MASC mimics papillary-cystic, microcystic, and follicular-type acinic cell carcinoma (AciCC) and low-grade cribriform cystadenocarcinoma (LGCCC) of the salivary gland. Using histology, immunohistochemistry (IHC), and molecular genetic techniques, we reevaluated 18 cases originally diagnosed as AciCC between 1993 and 2012. The last of these methods was used to detect the ETV6-NTRK3 translocation. The results reconfirmed 6 cases as AciCC (3 men; average age, 63 years) and helped us reclassify 10 cases as MASC (6 men; mean age, 46 years) and 2 as LGCCC (2 women; mean age, 48 years). Using IHC, we identified the 3 histologic types according to the expression patterns of vimentin, high-molecular-weight cytokeratin, cytokeratin 19, S-100, mammaglobin, MUC1, GATA-binding protein 3, adipophilin, α-amylase, DOG-1, SOX-10, and p63. The number of tumors diagnosed as MASC indicates that AciCC includes bona fide MASC cases. Because differential diagnosis among zymogen granule-poor AciCC, MASC, and LGCCC tumors is challenging, we recommend using molecular genetic tests for ETV6-NTRK3 for accurate diagnosis. Furthermore, detailed analyses of hematoxylin and eosin-stained tissues and IHC studies using the markers described here should be incorporated into routine practices. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. PTEN Loss in E-Cadherin-Deficient Mouse Mammary Epithelial Cells Rescues Apoptosis and Results in Development of Classical Invasive Lobular Carcinoma

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    Mirjam C. Boelens

    2016-08-01

    Full Text Available Invasive lobular carcinoma (ILC is an aggressive breast cancer subtype with poor response to chemotherapy. Besides loss of E-cadherin, a hallmark of ILC, genetic inactivation of PTEN is frequently observed in patients. Through concomitant Cre-mediated inactivation of E-cadherin and PTEN in mammary epithelium, we generated a mouse model of classical ILC (CLC, the main histological ILC subtype. While loss of E-cadherin induced cell dissemination and apoptosis, additional PTEN inactivation promoted cell survival and rapid formation of invasive mammary tumors that recapitulate the histological and molecular features, estrogen receptor (ER status, growth kinetics, metastatic behavior, and tumor microenvironment of human CLC. Combined inactivation of E-cadherin and PTEN is sufficient to cause CLC development. These CLCs showed significant tumor regression upon BEZ235-mediated inhibition of PI3K signaling. In summary, this mouse model provides important insights into CLC development and suggests inhibition of phosphatidylinositol 3-kinase (PI3K signaling as a potential therapeutic strategy for targeting CLC.

  16. Cytotoxicity and Apoptosis Induction of Ardisia crispa and Its Solvent Partitions against Mus musculus Mammary Carcinoma Cell Line (4T1

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    Muhammad Luqman Nordin

    2017-01-01

    Full Text Available This study was conducted to investigate the cytotoxicity and apoptosis effect of A. crispa extract and its solvent partition (ethyl acetate and aqueous extract against Mus musculus mammary carcinoma cell line (4T1. The normal mouse fibroblast cell line (NIH3T3 was used as comparison for selective cytotoxicity properties. The cytotoxicity evaluation was assessed using MTT assay. AO/PI dual fluorescent staining assay and Annexin V-FITC were used for apoptosis analysis. Results showed that 80% methanol extract from leaves showed most promising antimammary cancer agent with IC50 value of 42.26±1.82 μg/mL and selective index (SI value of 10.22. Ethyl acetate was cytotoxic for both cancer and normal cell while aqueous extract exhibited poor cytotoxic effect. 4T1 cells labelled with AO/PI and Annexin V-FITC and treated with 80% methanol extract demonstrated that the extract induces apoptosis to 4T1 mammary cancer cells. In conclusion, 80% methanol extract of A. crispa was selectively cytotoxic towards 4T1 cells but less cytotoxic towards NIH3T3 cells and induced the cancerous cells into apoptotic stage as early as 6 hours.

  17. Cytotoxicity and Apoptosis Induction of Ardisia crispa and Its Solvent Partitions against Mus musculus Mammary Carcinoma Cell Line (4T1).

    Science.gov (United States)

    Nordin, Muhammad Luqman; Abdul Kadir, Arifah; Zakaria, Zainul Amiruddin; Othman, Fauziah; Abdullah, Rasedee; Abdullah, Muhammad Nazrul Hakim

    2017-01-01

    This study was conducted to investigate the cytotoxicity and apoptosis effect of A. crispa extract and its solvent partition (ethyl acetate and aqueous extract) against Mus musculus mammary carcinoma cell line (4T1). The normal mouse fibroblast cell line (NIH3T3) was used as comparison for selective cytotoxicity properties. The cytotoxicity evaluation was assessed using MTT assay. AO/PI dual fluorescent staining assay and Annexin V-FITC were used for apoptosis analysis. Results showed that 80% methanol extract from leaves showed most promising antimammary cancer agent with IC50 value of 42.26 ± 1.82 μg/mL and selective index (SI) value of 10.22. Ethyl acetate was cytotoxic for both cancer and normal cell while aqueous extract exhibited poor cytotoxic effect. 4T1 cells labelled with AO/PI and Annexin V-FITC and treated with 80% methanol extract demonstrated that the extract induces apoptosis to 4T1 mammary cancer cells. In conclusion, 80% methanol extract of A. crispa was selectively cytotoxic towards 4T1 cells but less cytotoxic towards NIH3T3 cells and induced the cancerous cells into apoptotic stage as early as 6 hours.

  18. PTEN Loss in E-Cadherin-Deficient Mouse Mammary Epithelial Cells Rescues Apoptosis and Results in Development of Classical Invasive Lobular Carcinoma.

    Science.gov (United States)

    Boelens, Mirjam C; Nethe, Micha; Klarenbeek, Sjoerd; de Ruiter, Julian R; Schut, Eva; Bonzanni, Nicola; Zeeman, Amber L; Wientjens, Ellen; van der Burg, Eline; Wessels, Lodewyk; van Amerongen, Renée; Jonkers, Jos

    2016-08-23

    Invasive lobular carcinoma (ILC) is an aggressive breast cancer subtype with poor response to chemotherapy. Besides loss of E-cadherin, a hallmark of ILC, genetic inactivation of PTEN is frequently observed in patients. Through concomitant Cre-mediated inactivation of E-cadherin and PTEN in mammary epithelium, we generated a mouse model of classical ILC (CLC), the main histological ILC subtype. While loss of E-cadherin induced cell dissemination and apoptosis, additional PTEN inactivation promoted cell survival and rapid formation of invasive mammary tumors that recapitulate the histological and molecular features, estrogen receptor (ER) status, growth kinetics, metastatic behavior, and tumor microenvironment of human CLC. Combined inactivation of E-cadherin and PTEN is sufficient to cause CLC development. These CLCs showed significant tumor regression upon BEZ235-mediated inhibition of PI3K signaling. In summary, this mouse model provides important insights into CLC development and suggests inhibition of phosphatidylinositol 3-kinase (PI3K) signaling as a potential therapeutic strategy for targeting CLC. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Adaptation of Laser Microdissection Technique for the Study of a Spontaneous Metastatic Mammary Carcinoma Mouse Model by NanoString Technologies.

    Science.gov (United States)

    Castro, Nadia P; Merchant, Anand S; Saylor, Karen L; Anver, Miriam R; Salomon, David S; Golubeva, Yelena G

    2016-01-01

    Laser capture microdissection (LCM) of tissue is an established tool in medical research for collection of distinguished cell populations under direct microscopic visualization for molecular analysis. LCM samples have been successfully analyzed in a number of genomic and proteomic downstream molecular applications. However, LCM sample collection and preparation procedure has to be adapted to each downstream analysis platform. In this present manuscript we describe in detail the adaptation of LCM methodology for the collection and preparation of fresh frozen samples for NanoString analysis based on a study of a model of mouse mammary gland carcinoma and its lung metastasis. Our adaptation of LCM sample preparation and workflow to the requirements of the NanoString platform allowed acquiring samples with high RNA quality. The NanoString analysis of such samples provided sensitive detection of genes of interest and their associated molecular pathways. NanoString is a reliable gene expression analysis platform that can be effectively coupled with LCM.

  20. In vitro and in vivo antitumour effects of phenylboronic acid against mouse mammary adenocarcinoma 4T1 and squamous carcinoma SCCVII cells.

    Science.gov (United States)

    Marasovic, Maja; Ivankovic, Sinisa; Stojkovic, Ranko; Djermic, Damir; Galic, Borivoj; Milos, Mladen

    2017-12-01

    The cytotoxic activity of phenylboroxine acid was evaluated in vitro on mouse mammary adenocarcinoma 4T1, mouse squamous cell carcinoma SCCVII, hamster lung fibroblast V79 and mouse dermal fibroblasts L929 cell lines. The cytotoxic effects were dose dependent for all tested tumour and non-tumour cell lines. Under in vivo conditions, three application routes of phenylboronic acid were studied: intra-peritoneal (i.p.), intra-tumour (i.t.) and per-oral. After tumour transplantation in syngeneic mice, phenylboronic acid was shown to slow the growth of both tumour cell lines (4T1 and SCCVII) compared with the control. The inhibitory effects were pronounced during the application of phenylboronic acid. For both tested tumour cell lines, the most prominent antitumour effect was obtained by intraperitoneal administration, followed significantly by oral administration.

  1. Effects of limiting energy availability via diet and physical activity on mammalian target of rapamycin-related signaling in rat mammary carcinomas.

    Science.gov (United States)

    Jiang, Weiqin; Zhu, Zongjian; Thompson, Henry J

    2013-02-01

    This study evaluated how different approaches to limiting energy availability (LEA) by 15% affected mammalian target of rapamycin (mTOR)-related signaling in mammary carcinomas. Female Sprague Dawley rats, injected with 50mg 1-methyl-1-nitrosourea per kilogram body weight, were randomized to a control or three LEA interventions: (i) sedentary and restricted rats fed to 85% of energy available to the control or motorized wheel running (37 m/min) for an average of (ii) 1621 ± 55 (WRL) or (iii) 3094 ± 126 (WRH) meters/day with food intake adjusted to provide the same net amount of available energy across LEA interventions. Under these conditions, LEA reduced overall cancer burden by 28% (P = 0.04) and down-regulated mTOR-related signaling (Hotelling multivariate, P = 0.002). Among the regulatory nodes assessed, reduced levels of activated protein kinase B (pAkt) and induction of sirtuin 1 (SIRT1) were the most influential factors in distinguishing between sham control and LEA carcinomas. P-Akt was predictive of observed changes in levels of proteins involved in cell cycle control (r = 0.698, P < 0.0001) and induction of apoptosis (r = -0.429, P = 0.014). Plasma insulin and leptin were strongly associated with carcinoma pAkt levels. Consistent with downregulation of mTOR-related signaling by LEA, evidence of decreased lipid synthesis in carcinomas was observed (Hotelling multivariate, P < 0.001) and was negatively correlated with SIRT1 induction. Despite large differences between control and LEA, effects on mTOR regulation were insufficient to distinguish among LEA intervention groups. Given the modest effects observed on the LKB1/AMP-activated protein kinase regulatory node, NADH and NADPH rather than ATP may be more limiting for tumor growth when LEA is 15%.

  2. Mammary analog secretory carcinoma of salivary gland with high-grade histology arising in hard palate, report of a case and review of literature

    Science.gov (United States)

    Luo, Wenyi; Lindley, Sarah W; Lindley, Peter H; Krempl, Gregory A; Seethala, Raja R; Fung, Kar-Ming

    2014-01-01

    Mammary gland analog secretary carcinoma (MASC) of salivary gland is typically a tumor of low histologic grade and behaves as a low-grade malignancy with relatively benign course. This tumor shares histologic features, immunohistochemical profile, and a highly specific genetic translocation, ETV6-NTRK3, with secretory carcinoma of breast. Histologically, it is often mistaken as acinic cell carcinoma, adenocarcinoma not otherwise specified, and other primary salivary gland tumors. Here we report a case of MASC with high-grade transformation and cervical lymph node metastases confirmed with ETV6-NTRK3 translocation arising in the hard palate of a 41 year-old adult. Interestingly, the metastatic carcinoma has lower grade than the original tumor which strongly support malignant transformation of the original tumor. Most commonly, MASC arises from the parotid gland and less often in minor salivary glands. Metastasis is relatively uncommon and high-grade histology has only been reported in four cases with three of them arising from the parotid gland and the location of the fourth one has not been reported. This is the first case with high grade histology that arise from minor salivary gland and it emphasizes the importance of molecular screening of salivary gland tumor with high-grade histology for ETV6-NTRK3 translocation. In our literature of 115 cases that includes the current case, MASC occurred predominantly in adult with only a few cases under 18 years of age and a male to female ratio of 1.2:1. Parotid gland is more commonly affected but there is also significant occurrence in minor salivary glands. Except for the cases with high grade histology, the overall prognosis is good. PMID:25674280

  3. Mammary analogue secretory carcinoma of the parotid gland as a secondary malignancy in a childhood survivor of atypical teratoid rhabdoid tumor.

    Science.gov (United States)

    Woo, Jennifer; Seethala, Raja R; Sirintrapun, S Joseph

    2014-06-01

    We report the first case of mammary analogue secretory carcinoma (MASC) arising as a secondary malignancy in a 14 years old child with a history of atypical teratoid rhabdoid tumor (ATRT). Although MASC and ATRT are both rare malignancies, they do not share the same genetic and molecular profiles. MASC is a salivary malignancy characterized by a t(12;15)(p13;q25) translocation, resulting in an ETV6-NTRK3 fusion product encoding for a tyrosine kinase. ATRT is a highly malignant pediatric tumor characterized by a chromosome 22 mutation in the hSNF5/INI1 gene, encoding for a chromatin remodeling protein. Additionally, although mucoepidermoid carcinoma has been described as a secondary malignancy post-therapy for head and neck tumors, MASC has only been reported as a primary malignancy. Our patient was treated with a complete resection of his left sided ATRT at age 3 followed postoperatively with chemoradiotherapy. At age 14 he underwent a parotidectomy for his 1 year history of a left sided preauricular mass and was subsequently diagnosed with MASC. We not only report a case of two rare malignancies in one patient, but also the first case of MASC arising as a secondary malignancy.

  4. Difficulty in the Cytodiagnosis of Mammary Analogue Secretory Carcinoma: Survey of 109 Cytologists with a Case Originating from a Minor Salivary Gland.

    Science.gov (United States)

    Kai, Keita; Minesaki, Akimichi; Suzuki, Kumiko; Monji, Mikio; Nakamura, Mitsuo; Tsugitomi, Hisayuki; Kuratomi, Yuichiro; Aishima, Shinichi

    2017-07-25

    Mammary analogue secretory carcinoma (MASC) of the salivary gland shows morphologic similarities and shares an immunophenotype and characteristic ETV6-NTRK3 translocation with secretory carcinoma of the breast. We present a buccal case of MASC along with a survey-based debate about its cytologic diagnosis by fine-needle aspiration (FNA). FNA of the buccal nodule of a 58-year-old Japanese man was initially performed by 3 cytologists who gave different assessments of the Papanicolaou classification (i.e., class II, III, and V). To investigate the potential for discrepant diagnosis of MASC on a larger scale, we distributed a survey with questions about the cytological diagnosis of the present case to cytologists at other institutions. A total of 109 cytologists completed the survey, providing varying assessments of the Papanicolaou classification: class I/II (14%), class III (53%), and class IV/V (33%). Most of the respondents (72%) could not identify a particular tumor or disease. Even the respondents who identified a particular tumor suggested widely differing diagnoses, from a benign lesion to various malignant tumors. Only 2 respondents correctly identified MASC. Our experience and the results of the survey suggest difficulty in the cytodiagnosis of MASC. © 2017 S. Karger AG, Basel.

  5. What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC).

    Science.gov (United States)

    Drilon, A; Li, G; Dogan, S; Gounder, M; Shen, R; Arcila, M; Wang, L; Hyman, D M; Hechtman, J; Wei, G; Cam, N R; Christiansen, J; Luo, D; Maneval, E C; Bauer, T; Patel, M; Liu, S V; Ou, S H I; Farago, A; Shaw, A; Shoemaker, R F; Lim, J; Hornby, Z; Multani, P; Ladanyi, M; Berger, M; Katabi, N; Ghossein, R; Ho, A L

    2016-05-01

    Mammary analogue secretory carcinoma (MASC) is a recently described pathologic entity. We report the case of a patient with an initial diagnosis of salivary acinic cell carcinoma later reclassified as MASC after next-generation sequencing revealed an ETV6-NTRK3 fusion. This alteration was targeted with the pan-Trk inhibitor entrectinib (Ignyta), which possesses potent in vitro activity against cell lines containing various NTRK1/2/3 fusions. A dramatic and durable response was achieved with entrectinib in this patient, followed by acquired resistance that correlated with the appearance of a novel NTRK3 G623R mutation. Structural modeling predicts that this alteration sterically interferes with drug binding, correlating to decreased sensitivity to drug inhibition observed in cell-based assays. This first report of clinical activity with TrkC inhibition and the development of acquired resistance in an NTRK3-rearranged cancer emphasize the utility of comprehensive molecular profiling and targeted therapy for rare malignancies (NCT02097810). © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

  6. Molecular analysis of a mammary analog secretory carcinoma in the upper lip: Novel search for genetic and epigenetic abnormalities in MASC.

    Science.gov (United States)

    Abe, Masanobu; Inaki, Ryoko; Kanno, Yuki; Hoshi, Kazuto; Takato, Tsuyoshi

    2015-01-01

    Mammary analog secretory carcinoma (MASC) is a newly described rare malignancy of the salivary glands characterized by an ETS variant 6 (ETV6)-neurotrophic tyrosine kinase receptor type 3 (NTRK3) fusion gene (EN fusion gene). We present a case of MASC derived from the left upper lip in a 61-year-old woman. ETV6 rearrangement was detected by fluorescence in situ hybridization (FISH). The presence of EN fusion transcripts was verified by reverse-transcriptase polymerase chain reaction (RT-PCR) and sequencing of the PCR products. Accordingly, this tumor was diagnosed as MASC. Moreover, we performed mutation analysis of the 50 known cancer-related genes using next-generation sequencing. No mutation of cancer-related genes was identified here. Subsequently, the methylation status in promoter region of tumor-suppressor genes, RASSF1A and RARB2, was examined. Both genes have been reported to be methylated in malignant salivary gland tumors, but they were found to be unmethylated. Recent studies have demonstrated that distinct types of malignant salivary gland carcinomas are driven by specific, highly recurrent genetic alterations. Detection of molecular abnormalities could be powerful diagnostic tools in the field of salivary gland tumors in near future. We experienced a rare malignant salivary gland carcinoma, MASC. We diagnosed this tumor by molecular approach and subsequently tried to identify novel molecular abnormalities. Although no novel molecular alteration except for EN fusion gene was identified, this result might represent the favorable prognosis of patients with MASC. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Immunohistochemical Expression Profiles of Cell Adhesion Molecules, Matrix Metalloproteinases and their Tissue Inhibitors in Central and Peripheral Neoplastic Foci of Feline Mammary Carcinoma.

    Science.gov (United States)

    Pisamai, S; Rungsipipat, A; Kunnasut, N; Suriyaphol, G

    Feline mammary carcinoma (FMC) is a common cancer with high metastatic potential and high mortality rate. Loss of cell-cell interactions and degradation of the extracellular matrix by proteinases enhances tumour invasion and metastasis. Peripheral neoplastic foci (PNF) are defined as the presence of discrete tumour cell clusters, splitting off from central neoplastic foci (CNF) and lodging around these CNF. PNF therefore locate at the tumour-host interface at the site of invasion. The aim of this study was to evaluate immunohistochemically the expression of cell adhesion molecules (e-cadherin [CDH-1], syndecan 1 [SDC-1] and nectin-2), matrix metalloproteinases (matrix metalloproteinase [MMP]-2, MMP-7 and MMP-9) and their tissue inhibitors (tissue inhibitor of matrix metalloproteinase [TIMP]-1 and TIMP-2) together with the cellular proliferation marker, Ki67, in CNF and PNF of FMCs of different clinical stages and histological grades. Compared with control sections from areas of mammary gland hyperplasia, lower expression of MMP-7 and TIMP-2 was observed in all stages. Increased expression of TIMP-1 was observed in PNF in early-stage disease with no metastasis, while marked expression of CDH-1 and Ki67 occurred in late-stage FMC. In addition, the expression of MMP-2, MMP-9 and TIMP-1 in PNF of tumours with high histological grade (grade III) was higher than in low-grade tumours. The observed divergent protein expression in PNF could potentially form the basis of acting as novel markers in FMC. Potential markers may include the expression of TIMP-1 in PNF in early stage lesions, the expression of CDH-1 and Ki67 in late stages and the expression of MMP-2, MMP-9 and TIMP-1 in high-grade tumours. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Decreased adrenal medullary tyrosine hydroxylase mRNA in DMBA (7,12-dimethylbenz(a)anthracene)-induced mammary carcinoma

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    Bunce, O.R.; Badary, O.A.; Abou El-Ela, S.; Hartle, D.K. (Univ. of Georgia, Athens (United States))

    1991-03-15

    Adrenal cortical hormones suppress initiation and promotion of DMBA-induced mammary tumorigenesis. The authors found a positive correlation between presence of DMBA-induced adrenal cortical necrosis and mammary tumor incidence. Because they find adrenal medullary as well as cortical lesions in tumor bearing (TB) DMBA-treated rats, they evaluated medullary function by quantitating hybridized cDNA- TH-S{sup 35} with in situ TH-mRNA u sing computer assisted quantitative autoradiographic technique. Virgin female Sprague-Dawley rats were given a 10 mg i.g. dose of DMBA. Three wks later, rats were placed on 20% polyunsaturated (PUFA) fat diets containing omega-6 and omega-3 fatty acids. All were killed 15 wks post-DMBA. TH-mRNA levels in adrenal medullae of TB animals were decreased compared to non-TB rats. Histopathology indicated a high incidence of medullary necrosis in TB rats, whereas, adrenal necrosis did not occur in non-TB animals. Adrenal necrosis correlated positively with tumor burden, but no correlation was found between incidence of adrenal lesions and type of PUFA in the diet. The authors suggest that DMBA adrenal necrosis may reduce TH-mRNA in the medulla, compromise its catecholamine synthetic capability, and thereby contribute to the overall metabolic stress condition of TB rats.

  9. Lymph vascular invasion in invasive mammary carcinomas identified by the endothelial lymphatic marker D2-40 is associated with other indicators of poor prognosis

    Directory of Open Access Journals (Sweden)

    Rocha Gislene FS

    2008-02-01

    Full Text Available Abstract Background Immunohistochemical studies of lymphatic vessels have been limited by a lack of specific markers. Recently, the novel D2-40 antibody, which selectively marks endothelium of lymphatic vessels, was released. The aim of our study is to compare lymphatic and blood vessel invasion detected by hematoxylin and eosin (H&E versus that detected by immunohistochemistry, relating them with morphologic and molecular prognostic factors. Methods We selected 123 cases of invasive mammary carcinomas stratified into three subgroups according to axillary lymph node status: macrometastases, micrometastases, and lymph node negative. Lymphatic (LVI and blood (BVI vessel invasion were evaluated by H&E and immunohistochemistry using the D2-40 and CD31 antibodies, and related to histologic tumor type and grade, estrogen and progesterone receptors, E-cadherin, Ki67, p53, and Her2/neu expression. Results LVI was detected in H&E-stained sections in 17/123 cases (13.8%, and in D2-40 sections in 35/123 cases (28.5% (Kappa = 0.433. BVI was detected in H&E-stained sections in 5/123 cases (4.1%, and in CD31 stained sections in 19/123 cases (15.4% (Kappa = 0.198. LVI is positively related to higher histologic grade (p = 0.013, higher Ki67 expression (p = 0.00013, and to the presence of macrometastases (p = 0.002, and inversely related to estrogen (p = 0.0016 and progesterone (p = 0.00017 receptors expression. Conclusion D2-40 is a reliable marker of lymphatic vessels and is a useful tool for lymphatic emboli identification in immunostained sections of breast carcinomas with higher identification rates than H&E. Lymphatic vessel invasion was related to other features (high combined histologic grade, high Ki67 score, negative hormone receptors expression associated with worse prognosis, probable reflecting a potential for lymphatic metastatic spread and aggressive behavior.

  10. Tumor microvasculature observed using different contrast agents: a comparison between Gd-DTPA-Albumin and B-22956/1 in an experimental model of mammary carcinoma.

    Science.gov (United States)

    Boschi, Federico; Marzola, Pasquina; Sandri, Marco; Nicolato, Elena; Galiè, Mirco; Fiorini, Silvia; Merigo, Flavia; Lorusso, Vito; Chaabane, Linda; Sbarbati, Andrea

    2008-05-01

    The aim of this study was to compare a pure macromolecular contrast agent (Gd-DTPA-albumin) with a new protein-binding blood pool contrast agent (B22956/1) in terms of their capacity to investigate the microvasculature in an experimental model of mammary carcinoma. Tumors were induced by subcutaneous injection of 5 x 10(5) BB1 cells into the backs of 5-7 week-old female FVB/neuNT233 mice. The animals were observed using DCE-MRI when the longest diameter of the tumor was 10.2+/-2.0 mm. DCE-MRI experiments were carried out using B22956/1 and (24 h later) Gd-DTPA-albumin. DCE-MRI data showed that vasculature in the tumor rim was characterized by greater fractional plasma volume and transendothelial permeability than vasculature in the tumor core as measured by both contrast agents. Permeability to Gd-DTPA-albumin in the tumor core was hardly measurable while permeability to B22956/1 was substantial. Histologically the tumor core showed areas of well vascularized, viable tissue surrounded by necrotic regions. DCE-MRI experiments performed with B22956/1 are useful in the investigation of vasculature in those tumor regions that are characterized by low permeability to macromolecules.

  11. Adaptation of Laser Microdissection Technique for the Study of a Spontaneous Metastatic Mammary Carcinoma Mouse Model by NanoString Technologies.

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    Nadia P Castro

    Full Text Available Laser capture microdissection (LCM of tissue is an established tool in medical research for collection of distinguished cell populations under direct microscopic visualization for molecular analysis. LCM samples have been successfully analyzed in a number of genomic and proteomic downstream molecular applications. However, LCM sample collection and preparation procedure has to be adapted to each downstream analysis platform. In this present manuscript we describe in detail the adaptation of LCM methodology for the collection and preparation of fresh frozen samples for NanoString analysis based on a study of a model of mouse mammary gland carcinoma and its lung metastasis. Our adaptation of LCM sample preparation and workflow to the requirements of the NanoString platform allowed acquiring samples with high RNA quality. The NanoString analysis of such samples provided sensitive detection of genes of interest and their associated molecular pathways. NanoString is a reliable gene expression analysis platform that can be effectively coupled with LCM.

  12. NOTE: Clinical application of a OneDose™ MOSFET for skin dose measurements during internal mammary chain irradiation with high dose rate brachytherapy in carcinoma of the breast

    Science.gov (United States)

    Kinhikar, Rajesh A.; Sharma, Pramod K.; Tambe, Chandrashekhar M.; Mahantshetty, Umesh M.; Sarin, Rajiv; Deshpande, Deepak D.; Shrivastava, Shyam K.

    2006-07-01

    In our earlier study, we experimentally evaluated the characteristics of a newly designed metal oxide semiconductor field effect transistor (MOSFET) OneDose™ in-vivo dosimetry system for Ir-192 (380 keV) energy and the results were compared with thermoluminescent dosimeters (TLDs). We have now extended the same study to the clinical application of this MOSFET as an in-vivo dosimetry system. The MOSFET was used during high dose rate brachytherapy (HDRBT) of internal mammary chain (IMC) irradiation for a carcinoma of the breast. The aim of this study was to measure the skin dose during IMC irradiation with a MOSFET and a TLD and compare it with the calculated dose with a treatment planning system (TPS). The skin dose was measured for ten patients. All the patients' treatment was planned on a PLATO treatment planning system. TLD measurements were performed to compare the accuracy of the measured results from the MOSFET. The mean doses measured with the MOSFET and the TLD were identical (0.5392 Gy, 15.85% of the prescribed dose). The mean dose was overestimated by the TPS and was 0.5923 Gy (17.42% of the prescribed dose). The TPS overestimated the skin dose by 9% as verified by the MOSFET and TLD. The MOSFET provides adequate in-vivo dosimetry for HDRBT. Immediate readout after irradiation, small size, permanent storage of dose and ease of use make the MOSFET a viable alternative for TLDs.

  13. Insight into the effect of the vasopressin analog desmopressin on lung colonization by mammary carcinoma cells in BALB/c mice.

    Science.gov (United States)

    Garona, Juan; Pifano, Marina; Scursoni, Alejandra M; Gomez, Daniel E; Alonso, Daniel F; Ripoll, Giselle V

    2014-09-01

    Desmopressin (dDAVP) is a synthetic peptide analog of vasopressin with antidiuretic and hemostatic properties. Recent experimental evidence have suggested that dDAVP can inhibit metastasis formation by agonist action on V2 vasopressin receptors present in both tumor and endothelial cells. We have examined the kinetics of dDAVP effect during metastatic colonization and its potential association with hemostasis. The experimental metastasis assay was performed by injecting F3II mammary carcinoma cells into the lateral tail vein of syngeneic female BALB/c mice. Clinically relevant doses of dDAVP (0.3 to 2 μg/kg intravenously (i.v.)) produced a dose-dependent inhibition in the formation of lung nodules when administered during the first 24 hours after F3II tumor cell injection. The hemostatic agent tranexamic acid (10 mg/kg, i.v.) had no effect on metastasis formation in the same experimental conditions, while the anticoagulant enoxaparin (1 mg/kg, subcutaneously (s.c.)) did not modify the antimetastatic action of dDAVP. In vitro, dDAVP had a strong inhibitory effect on F3II cell colony formation. dDAVP interferes with early metastatic disease, and direct association of this effect with hemostatic mechanisms is unlikely. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Clinical application of a OneDose MOSFET for skin dose measurements during internal mammary chain irradiation with high dose rate brachytherapy in carcinoma of the breast.

    Science.gov (United States)

    Kinhikar, Rajesh A; Sharma, Pramod K; Tambe, Chandrashekhar M; Mahantshetty, Umesh M; Sarin, Rajiv; Deshpande, Deepak D; Shrivastava, Shyam K

    2006-07-21

    In our earlier study, we experimentally evaluated the characteristics of a newly designed metal oxide semiconductor field effect transistor (MOSFET) OneDose in-vivo dosimetry system for Ir-192 (380 keV) energy and the results were compared with thermoluminescent dosimeters (TLDs). We have now extended the same study to the clinical application of this MOSFET as an in-vivo dosimetry system. The MOSFET was used during high dose rate brachytherapy (HDRBT) of internal mammary chain (IMC) irradiation for a carcinoma of the breast. The aim of this study was to measure the skin dose during IMC irradiation with a MOSFET and a TLD and compare it with the calculated dose with a treatment planning system (TPS). The skin dose was measured for ten patients. All the patients' treatment was planned on a PLATO treatment planning system. TLD measurements were performed to compare the accuracy of the measured results from the MOSFET. The mean doses measured with the MOSFET and the TLD were identical (0.5392 Gy, 15.85% of the prescribed dose). The mean dose was overestimated by the TPS and was 0.5923 Gy (17.42% of the prescribed dose). The TPS overestimated the skin dose by 9% as verified by the MOSFET and TLD. The MOSFET provides adequate in-vivo dosimetry for HDRBT. Immediate readout after irradiation, small size, permanent storage of dose and ease of use make the MOSFET a viable alternative for TLDs.

  15. Loss of heterozygosity in mammary serine protease inhibitor (maspin) and p53 at chromosome 17 and 18 in oral cavity squamous cell carcinoma.

    Science.gov (United States)

    Choi, Kyu Young; Choi, Hyung-Joon; Chung, Eun-Jae; Lee, Dong Jin; Kim, Jin Hwan; Rho, Young-Soo

    2015-09-01

    The purpose of this study was to evaluate the loss of heterozygosity (LOH) in chromosomes 17p13 (p53 gene) and in 18q21 (mammary serine protease inhibitor [maspin] gene), and the expression of both genes in tissues, in patients with oral cavity squamous cell carcinoma (SCC). Thirty patients with oral cavity SCC have been evaluated for the presence of LOH in chromosomes 17p13 and 18q21, and the expression of p53 and maspin in tissues. Clinicopathological features and survival in these patients were also analyzed. LOH in 17p13 was more frequently identified in patients with lymph node metastasis and/or high TNM classification. LOH in 18q21 was more frequently identified in high primary T classification patients. Increased expression rate of p53 and/or decreased maspin expression rate were significantly higher in oral cavity SCC than normal tissues. LOH on chromosome 17, 18, the expression of p53, and maspin are related to the carcinogenesis of oral cavity SCC. Relationships with clinicopathological factors in oral cavity SCC were also revealed. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1239-1245, 2015. © 2014 Wiley Periodicals, Inc.

  16. Urachal Carcinoma with Choroidal, Lung, Lymph Node, Adrenal, Mammary, and Bone Metastases and Peritoneal Carcinomatosis Showing Partial Response after Chemotherapy Treatment with a Modified Docetaxel, Cisplatin and 5-Fluorouracil Regimen

    Directory of Open Access Journals (Sweden)

    Kathleen Dekeister

    2016-04-01

    Full Text Available Urachal carcinoma (UC is a rare tumor mainly affecting middle-aged males. Metastases occur most frequently in lymph nodes and the lungs. There are no standard adjuvant and metastatic treatments. We report the case of a 36-year-old female with UC treated with partial cystectomy who relapsed 3 years after surgery with left choroidal, lung, mediastinal lymph node, right adrenal, mammary, and bone metastases as well as peritoneal carcinomatosis. She obtained a partial response after 10 cycles of chemotherapy with a modified docetaxel, cisplatin and 5-fluorouracil (mTPF regimen. This is the first report on the use of the mTPF regimen in UC and on the existence of choroidal, adrenal, and mammary metastases.

  17. RU 58,668, a new pure antiestrogen inducing a regression of human mammary carcinoma implanted in nude mice.

    Science.gov (United States)

    Van de Velde, P; Nique, F; Bouchoux, F; Brémaud, J; Hameau, M C; Lucas, D; Moratille, C; Viet, S; Philibert, D; Teutsch, G

    1994-02-01

    RU 58,668, a new steroidal antiestrogen, has been synthesized. Its in vitro and in vivo pharmacological activities have been compared to those of tamoxifen and ICI 182,780. In vitro, it displayed affinities for human and murine estrogen receptors equivalent to those of 4-hydroxy-tamoxifen, along with moderate affinities for progestin and glucocorticoid receptors. RU 58,668 proved to be a potent antiproliferative agent on MCF-7 cells stimulated by estradiol, or by exogenous or endogenous growth factors (IC50, 0.01 nM). It also inhibited the growth of the insulin-stimulated T47D cell line. In vivo, RU 58,668 displayed a total anti-uterotrophic activity in mice or rats without exhibiting any agonistic effect. Moreover, RU 58,668 was the only antiestrogenic compound tested so far to be able to induce a long term regression of human mammary MCF-7 tumors implanted in nude mice, suggesting its potential use for the treatment of advanced breast cancer.

  18. Mammary gland stem cells

    DEFF Research Database (Denmark)

    Fridriksdottir, Agla J R; Petersen, Ole W; Rønnov-Jessen, Lone

    2011-01-01

    Distinct subsets of cells, including cells with stem cell-like properties, have been proposed to exist in normal human breast epithelium and breast carcinomas. The cellular origins of epithelial cells contributing to gland development, tissue homeostasis and cancer are, however, still poorly...... and differences between mouse and human gland development with particular emphasis on the identity and localization of stem cells, and the influence of the surrounding microenvironment. It is concluded that while recent advances in the field have contributed immense insight into how the normal mammary gland...... develops and is maintained, significant discrepancies exist between the mouse and human gland which should be taken into consideration in current and future models of mammary stem cell biology....

  19. Role of a polyphenol-enriched preparation on chemoprevention of mammary carcinoma through cancer stem cells and inflammatory pathways modulation.

    Science.gov (United States)

    Vuong, Tri; Mallet, Jean-François; Ouzounova, Maria; Rahbar, Sam; Hernandez-Vargas, Hector; Herceg, Zdenko; Matar, Chantal

    2016-01-14

    Naturally occurring polyphenolic compounds from fruits, particularly from blueberries, have been reported to be significantly involved in cancer chemoprevention and chemotherapy. Biotransformation of blueberry juice by Serratia vaccinii increases its polyphenolic content and endows it with anti-inflammatory properties. This study evaluated the effect of a polyphenol-enriched blueberry preparation (PEBP) and its non-fermented counterpart (NBJ), on mammary cancer stem cell (CSC) development in in vitro, in vivo and ex vivo settings. Effects of PEBP on cell proliferation, mobility, invasion, and mammosphere formation were measured in vitro in three cell lines: murine 4T1 and human MCF7 and MDA-MB-231. Ex vivo mammosphere formation, tumor growth and metastasis observations were carried out in a BALB/c mouse model. Our research revealed that PEBP influence cellular signaling cascades of breast CSCs, regulating the activity of transcription factors and, consequently, inhibiting tumor growth in vivo by decreasing metastasis and controlling PI3K/AKT, MAPK/ERK, and STAT3 pathways, central nodes in CSC inflammatory signaling. PEBP significantly inhibited cell proliferation of 4T1, MCF-7 and MDA-MB-231. In all cell lines, PEBP reduced mammosphere formation, cell mobility and cell migration. In vivo, PEBP significantly reduced tumor development, inhibited the formation of ex vivo mammospheres, and significantly reduced lung metastasis. This study showed that polyphenol enrichment of a blueberry preparation by fermentation increases its chemopreventive potential by protecting mice against tumor development, inhibiting the formation of cancer stem cells and reducing lung metastasis. Thus, PEBP may represent a novel complementary alternative medicine therapy and a source for novel therapeutic agents against breast cancer.

  20. HER-2/neu immunoreactivity in invasive mammary carcinomas: a comparative study using monoclonal and polyclonal antibodies including the HercepTestTM

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    Gouvêa Agostinho Pinto

    2004-01-01

    Full Text Available INTRODUCTION: HER-2/neu overexpression has been tested using immunohistochemistry as a reliable and cost-effective method to select patients with invasive mammary carcinomas (IMC for trastuzumab treatment, but there is no consensus regarding the best antibody to be used. The aim of the present study was to test five different antibodies for determining the status of HER-2/neu overexpression in IMC. MATERIAL AND METHODS: Sixty-six formalin-fixed, paraffin-embedded IMC were investigated by immunohistochemistry, using two polyclonal antibodies, HercepTestTM (Dako and A0485 (Dako, and three monoclonal antibodies, the clone CB11, from both Novocastra Laboratories and from Biogenex, and the clone 4D5 (Genentech. All immunostainings were scored according to the guidelines for the HercepTestTM. RESULTS: The A0485 was positive in 25 cases (37.9%. The HercepTestTM was positive in 14/66 cases (21.2%. Both CB11 antibodies yielded a positive reaction in the same nine patients (13.6%. The 4D5 was positive in only 4/66 cases (6.1%. All positive cases for CB11 or 4D5 were HercepTestTMpositive. All cases positive for HercepTestTM were positive for A0485. Most of the HercepTestTM and A0485 2+ cases were negative when using the other antibodies. DISCUSSION: There was a higher number of cases presenting HER-2/neu positivity with the A0485 and HercepTestTM than with the other antibodies, primarily in cases scored as 2+. There was no difference in positivity when the CB11Ab was used, regardless of company. CONCLUSION: The use of immunohistochemistry for the clinical assessment of HER-2/neu overexpression still needs prospective validation.

  1. Conditionally reprogrammed normal and transformed mouse mammary epithelial cells display a progenitor-cell-like phenotype.

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    Francisco R Saenz

    Full Text Available Mammary epithelial (ME cells cultured under conventional conditions senesce after several passages. Here, we demonstrate that mouse ME cells isolated from normal mammary glands or from mouse mammary tumor virus (MMTV-Neu-induced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (CRCs on irradiated fibroblasts in the presence of the Rho kinase inhibitor Y-27632. Cell surface progenitor-associated markers are rapidly induced in normal mouse ME-CRCs relative to ME cells. However, the expression of certain mammary progenitor subpopulations, such as CD49f+ ESA+ CD44+, drops significantly in later passages. Nevertheless, mouse ME-CRCs grown in a three-dimensional extracellular matrix gave rise to mammary acinar structures. ME-CRCs isolated from MMTV-Neu transgenic mouse mammary tumors express high levels of HER2/neu, as well as tumor-initiating cell markers, such as CD44+, CD49f+, and ESA+ (EpCam. These patterns of expression are sustained in later CRC passages. Early and late passage ME-CRCs from MMTV-Neu tumors that were implanted in the mammary fat pads of syngeneic or nude mice developed vascular tumors that metastasized within 6 weeks of transplantation. Importantly, the histopathology of these tumors was indistinguishable from that of the parental tumors that develop in the MMTV-Neu mice. Application of the CRC system to mouse mammary epithelial cells provides an attractive model system to study the genetics and phenotype of normal and transformed mouse epithelium in a defined culture environment and in vivo transplant studies.

  2. A rare malignancy of the parotid gland in a 13-year-old Taiwanese boy: case report of a mammary analogue secretory carcinoma of the salivary gland with molecular study.

    Science.gov (United States)

    Hwang, Michael J; Wu, Pei Ru; Chen, Chih-Ming; Chen, Chia-Yu; Chen, Chih-Jung

    2014-03-01

    Mammary analogue secretory carcinoma (MASC) is a recently described malignancy of the salivary glands characterized by an ETV6-NTRK3 (EN) fusion gene. Morphologically, MASC is sometimes difficult to distinguish from acinic cell carcinoma. Consequently, identifying the chromosomal translocation is essential for diagnosis. We present a case of parotid gland MASC in a 13-year-old boy. To the best of our knowledge, this is the youngest case reported in the literature. Histologic evaluation showed a tumor composed of microcysts, tubular structures, solid nests, or papillary architecture, with secretions within the lumens of the cysts or tubules. Immunohistochemically, tumor cells showed diffuse positive staining of S-100 protein, cytokeratin 19, and vimentin. ETV6 rearrangement was detected by fluorescence in situ hybridization and EN fusion transcripts were verified by reverse transcription (RT-PCR) assay.

  3. Morphologic Changes of Mammary Carcinomas in Mice over Time as Monitored by Flat-Panel Detector Volume Computed Tomography

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    Jeannine Missbach-Guentner

    2008-07-01

    Full Text Available Noninvasive methods are strongly needed to detect and quantify not only tumor growth in murine tumor models but also the development of vascularization and necrosis within tumors. This study investigates the use of a new imaging technique, flat-panel detector volume computed tomography (fpVCT, to monitor in vivo tumor progression and structural changes within tumors of two murine carcinoma models. After tumor cell inoculation, single fpVCT scans of the entire mice were performed at different time points. The acquired isotropic, high-resolution volume data sets enable an accurate real-time assessment and precise measurements of tumor volumes. Spreading of contrast agent-containing blood vessels around and within the tumors was clearly visible over time. Furthermore, fpVCT permits the identification of differences in the uptake of contrast media within tumors, thus delineating necrosis, tumor tissues, and blood vessels. Classification of tumor tissues based on the decomposition of the underlying mixture distribution of tissue-related Hounsfield units allowed the quantitative acquisition of necrotic tissues at each time point. Morphologic alterations of the tumor depicted by fpVCT were confirmed by histopathologic examination. Concluding, our data show that fpVCT may be highly suitable for the noninvasive evaluation of tumor responses to anticancer therapies during the course of the disease.

  4. Cdk2-Null Mice Are Resistant to ErbB-2-Induced Mammary Tumorigenesis

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    Dipankar Ray

    2011-05-01

    Full Text Available The concept of targeting G1 cyclin-dependent kinases (CDKs in breast cancer treatments is supported by the fact that the genetic ablation of Cdk4 had minimal impacts on normal cell proliferation in majority of cell types, resulting in near-normal mouse development, whereas such loss of Cdk4 completely abrogated ErbB-2/neu-induced mammary tumorigenesis in mice. In most human breast cancer tissues, another G1-regulatory CDK, CDK2, is also hyperactivated by various mechanisms and is believed to be an important therapeutic target. In this report, we provide genetic evidence that CDK2 is essential for proliferation and oncogenesis of murine mammary epithelial cells. We observed that 87% of Cdk2-null mice were protected from ErbB-2-induced mammary tumorigenesis. Mouse embryonic fibroblasts isolated from Cdk2-null mouse showed resistance to various oncogene-induced transformation. Previously, we have reported that hemizygous loss of Cdc25A, the major activator of CDK2, can also protect mice from ErbB-2-induced mammary tumorigenesis [Cancer Res (2007 67(14: 6605–11]. Thus, we propose that CDC25A-CDK2 pathway is critical for the oncogenic action of ErbB-2 in mammary epithelial cells, in a manner similar to Cyclin D1/CDK4 pathway.

  5. A comparative immunohistochemistry study of diagnostic tools in salivary gland tumors: usefulness of mammaglobin, gross cystic disease fluid protein 15, and p63 cytoplasmic staining for the diagnosis of mammary analog secretory carcinoma?

    Science.gov (United States)

    Projetti, Fabrice; Lacroix-Triki, Magali; Serrano, Elie; Vergez, Sebastien; Barres, Béatrice Herbault; Meilleroux, Julie; Delisle, Marie-Bernadette; Uro-Coste, Emmanuelle

    2015-04-01

    Mammary analog secretory carcinoma (MASC) of the salivary gland has been recently described according to morphological, immunohistochemical, and molecular (ETV6-NTRK3 translocation) similarities with the mammary secretory carcinoma. The most important differential diagnostic considerations of MASC are low-grade adenocarcinoma not otherwise specified (NOS), cystadenocarcinoma, and acinic cell carcinoma (AciCC). These tumors may share an overlapping morphology with MASC, and additional immunohistochemical studies are required to reinforce the diagnosis. Mammaglobin, GCDFP-15, and p63 staining have been reported in MASC. Our study was designed to check the specificity of these antibodies in MASC compared to other frequent tumors of salivary glands. A series of 62 salivary gland tumors [10 MASCs, 5 adenocarcinomas NOS and 2 cystadenocarcinomas with MASC features and without ETV6 rearrangement, one low-grade cribriform cystadenocarcinoma (LGCCC), 9 AciCCs, 10 MECs, 10 adenoid cystic carcinomas (AdeCCs), 5 polymorphous low-grade adenocarcinomas (PLGAs), and 10 pleomorphic adenomas (PAs)] was analyzed by immunohistochemistry with mammaglobin, GCDFP-15, and p63 antibodies. Positivity for mammaglobin was observed in all MASCs, cystadenocarcinomas, LGCCC, and PLGAs, in some adenocarcinomas NOS, PAs, and MECs, rarely in AciCCs and never in AdeCCs. Positivity for GCDFP-15 was observed in most of the tumor types except in AdeCCs. Interestingly, cytoplasmic positivity for p63 was observed in most of MASCs and PLGAs while rarely in adenocarcinomas NOS and PAs, and never in the other tumor types. Our study revealed the usefulness of mammaglobin and p63 cytoplasmic staining to define which tumors are worth to be screened for ETV6 rearrangement. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Pitfalls in Prediction Modeling for Normal Tissue Toxicity in Radiation Therapy: An Illustration With the Individual Radiation Sensitivity and Mammary Carcinoma Risk Factor Investigation Cohorts

    Energy Technology Data Exchange (ETDEWEB)

    Mbah, Chamberlain, E-mail: chamberlain.mbah@ugent.be [Department of Basic Medical Sciences, Faculty of Health Sciences, Ghent University, Ghent (Belgium); Department of Mathematical Modeling, Statistics, and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Ghent (Belgium); Thierens, Hubert [Department of Basic Medical Sciences, Faculty of Health Sciences, Ghent University, Ghent (Belgium); Thas, Olivier [Department of Mathematical Modeling, Statistics, and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Ghent (Belgium); National Institute for Applied Statistics Research Australia, University of Wollongong, Wollongong, New South Wales (Australia); De Neve, Jan [Department of Data Analysis, Faculty of Psychology and Educational Sciences, Ghent University, Ghent (Belgium); Chang-Claude, Jenny; Seibold, Petra; Botma, Akke [Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg (Germany); West, Catharine [Translational Radiobiology Group, Institute of Cancer Sciences, Radiotherapy Related Research, Christie Hospital NHS Trust, University of Manchester, Manchester (United Kingdom); De Ruyck, Kim [Department of Basic Medical Sciences, Faculty of Health Sciences, Ghent University, Ghent (Belgium)

    2016-08-01

    Purpose: To identify the main causes underlying the failure of prediction models for radiation therapy toxicity to replicate. Methods and Materials: Data were used from two German cohorts, Individual Radiation Sensitivity (ISE) (n=418) and Mammary Carcinoma Risk Factor Investigation (MARIE) (n=409), of breast cancer patients with similar characteristics and radiation therapy treatments. The toxicity endpoint chosen was telangiectasia. The LASSO (least absolute shrinkage and selection operator) logistic regression method was used to build a predictive model for a dichotomized endpoint (Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer score 0, 1, or ≥2). Internal areas under the receiver operating characteristic curve (inAUCs) were calculated by a naïve approach whereby the training data (ISE) were also used for calculating the AUC. Cross-validation was also applied to calculate the AUC within the same cohort, a second type of inAUC. Internal AUCs from cross-validation were calculated within ISE and MARIE separately. Models trained on one dataset (ISE) were applied to a test dataset (MARIE) and AUCs calculated (exAUCs). Results: Internal AUCs from the naïve approach were generally larger than inAUCs from cross-validation owing to overfitting the training data. Internal AUCs from cross-validation were also generally larger than the exAUCs, reflecting heterogeneity in the predictors between cohorts. The best models with largest inAUCs from cross-validation within both cohorts had a number of common predictors: hypertension, normalized total boost, and presence of estrogen receptors. Surprisingly, the effect (coefficient in the prediction model) of hypertension on telangiectasia incidence was positive in ISE and negative in MARIE. Other predictors were also not common between the 2 cohorts, illustrating that overcoming overfitting does not solve the problem of replication failure of prediction models completely

  7. Mammary Development and Breast Cancer: A Wnt Perspective

    Science.gov (United States)

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

    2016-01-01

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

  8. Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors.

    Science.gov (United States)

    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 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. © The Author(s) 2016.

  9. Similarity of GATA-3 Expression between Rat and Human Mammary Glands.

    Science.gov (United States)

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

    2014-07-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whole ductal epithelial cells were positive for GATA-3 in the nuclei. No positive cells were detected in rat or human fibroadenomas. In rat and human mammary carcinomas, the nuclei of proliferating luminal-derived cancer cells expressed GATA-3. Therefore, GATA-3 protein is a candidate marker for mammary carcinoma in rats as well as humans.

  10. Oxygen tension in mouse mammary carcinomas and osteosarcomas after irradiation with reactor fission neutrons; Pression en oxygene dans les carcinomes mammaires et les osteosacomes de la souris apres irradiation par neutrons de fission

    Energy Technology Data Exchange (ETDEWEB)

    Weissfloch, L.; Auberger, T.; Molls, M. [Clinic and Policlinic for Radiotherapy and Radiological Oncology, Ismaninger, Munich (Germany); Senekowitsch-Schmidtke, R. [Clinic and Policlinic for Nuclear Medicine, Klinikum Rechts der Isar, Munich (Germany); Wagner, F.M. [Reactor Station Garching, Munich (Germany); Tempel, K. [Institute for Pharmacology, Veterinary Faculty, Munich (Germany)

    1996-12-31

    Investigations were made on intratumoral oxygen tension after irradiations with reactor fission neutrons using the Eppendorf - pO{sub 2} -Histograph{sup R}. Iso-transplanted AT17-mammary carcinomas on C3H-mice and osteosarcomas OTS-64 on Balb c-mice received 2 or - Gy neutrons single dose. Before and at certain points of time after treatment the pO{sub 2}-values were evaluated. Some tumors with initially low median pO{sub 2}-values showed a short-lasting increase between 2 and 24 hours after irradiation. In the tumors with relatively high median pO{sub 2}-values before irradiation the pO{sub 2} decreased to hypoxic range. third group of tumors showed no significant changes after irradiation. None of the tumors stopped growth during the observation period. (author). 19 refs.

  11. Significance of EZH2 expression in canine mammary tumors.

    Science.gov (United States)

    Choi, Hyun-Ji; Jang, Sungwoong; Ryu, Jae-Eun; Lee, Hyo-Ju; Lee, Han-Byul; Ahn, Woo-Sung; Kim, Hye-Jin; Lee, Hyo-Jin; Lee, Hee Jin; Gong, Gyung-Yub; Son, Woo-Chan

    2016-08-09

    Current studies report that aberrations in epigenetic regulators or chromatin modifications are related to tumor development and maintenance. EZH2 (Enhancer of zeste homolog 2) is one of the catalytic subunits of Polycomb repressive complex 2, a crucial epigenetic regulator. EZH2 has a master regulatory function in such processes as cell proliferation, stem cell differentiation, and early embryogenesis. In humans, EZH2 is linked to oncogenic function in several carcinomas, including breast cancer, and dysregulation of EZH2 has been particularly associated with loss of differentiation and the development of poorly differentiated breast cancer. In our present study, we were interested in determining whether EZH2 is increased in canine mammary tumors, which show similarities to human breast cancer. Investigation of the expression of EZH2 in canine mammary tumors revealed that EZH2 protein was overexpressed in canine mammary carcinomas, as in human breast cancer. In addition, the immunohistochemical expression level of EZH2 was associated with the degree of malignancy in canine mammary carcinoma. This is the first report to describe EZH2 expression in canine mammary tumors. Because the expression of EZH2 was similar in canine mammary carcinoma and human breast cancer, spontaneous canine mammary tumors may be a suitable model for studying EZH2 and treatment development.

  12. Comparative analysis of peptidylarginine deiminase-2 expression in canine, feline and human mammary tumours.

    Science.gov (United States)

    Cherrington, B D; Mohanan, S; Diep, A N; Fleiss, R; Sudilovsky, D; Anguish, L J; Coonrod, S A; Wakshlag, J J

    2012-01-01

    The peptidylarginine deiminase (PAD) enzyme family converts arginine residues in proteins to citrulline. In the canine mammary gland, PAD2 expression is first detected in epithelial cells in oestrus and becomes more widely expressed during dioestrus. PAD2 appears to modify nuclear histones, suggesting a role for the enzyme in chromatin remodelling and gene regulation. Recent evidence suggests that PAD2 plays a role in gene regulation in primary human breast epithelial cells. PAD2 may therefore be involved in gene regulation as it relates to mammary development, the oestrus cycle and potentially to neoplasia. The aim of the present study was to determine whether PAD2 expression was increased or decreased in mammary carcinoma compared with normal mammary tissue. A human mammary tissue microarray and archival surgical biopsy tissues from canine and feline mammary tumours were used to demonstrate differential expression of PAD2 in mammary carcinoma that appeared to be consistent across species. Normal human and canine mammary epithelium showed strong cytoplasmic and nuclear expression of PAD2, but there was reduced PAD2 expression in mammary carcinomas from both species. Feline mammary carcinomas had complete loss of nuclear PAD2 expression. Loss of nuclear PAD2 expression may therefore represent a marker of progression towards more aggressive neoplasia. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

    Andreasen, Eva Bartholin; Nielsen, Ole Lerberg; Tranholm, M.

    2016-01-01

    Tissue factor (TF) expression in human cancers has been associated with a procoagulant state and facilitation of metastasis. This study was conducted in order to evaluate if TF was expressed in canine mammary tumours. Forty epithelial mammary tumours from 28 dogs were included. TF expression...... in a lymph node metastasis classified as anaplastic mammary carcinoma from a dog with concomitant disseminated intravascular coagulation (DIC)....

  14. Pro-inflammatory cytokines: Useful markers for the diagnosis of canine mammary tumours?

    Science.gov (United States)

    Andaluz, Ana; Yeste, Marc; Rodríguez-Gil, Joan E; Rigau, Teresa; García, Félix; Rivera del Álamo, Maria Montserrat

    2016-04-01

    The aim of the present study was to analyse the expression of 60 pro-inflammatory cytokines as possible markers of malignancy in canine mammary tumours using a human cytokine antibody array. The cytokines were grouped into two different categories: (1) cytokines in which expression indicated the presence of a mammary tumour and (2) cytokines in which expression differentiated between simple mammary adenoma, tubulopapillary carcinoma or complex carcinoma. These data suggest that specific pro-inflammatory cytokines could be useful as tools for the diagnosis of canine mammary tumours. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Investigations on the incidence of mammary carcinoma after X-ray therapy at the Gynecologic Hospital of the University of Marburg

    Energy Technology Data Exchange (ETDEWEB)

    Eulenburg, R.; Lauth, G.; Thein, T.

    1987-03-01

    A lot of women still object to mammography for fear of induction of carcinoma by radioactive rays. Even a large number of doctors are not informed about the fact that during the last ten years the dosis necessary for examination could be extremely reduced. In a follow-up examination of 61 females who had undergone a therapy of mastitis with a rayage of 3x80 R between 1949 and 1958, an enhanced risk of carcinoma could not be ascertained.

  16. Diagnostic utility of phosphorylated signal transducer and activator of transcription 5 immunostaining in the diagnosis of mammary analogue secretory carcinoma of the salivary gland: A comparative study of salivary gland cancers.

    Science.gov (United States)

    Kawahara, Akihiko; Taira, Tomoki; Abe, Hideyuki; Takase, Yorihiko; Kurita, Takashi; Sadashima, Eiji; Hattori, Satoshi; Imamura, Ichio; Matsumoto, Shinji; Fujisaki, Hitomi; Sueyoshi, Kazunobu; Akiba, Jun; Kage, Masayoshi

    2015-10-01

    Mammary analogue secretory carcinoma (MASC) with an ETS variant gene 6 (ETV6)-neurotrophic tyrosine kinase receptor type 3 (NTRK3) translocation is a newly described type of salivary gland cancer. It is known that overexpression of signal transducer and activator of transcription 5a (STAT5a) occurs in secretory carcinoma of the breast and MASC, and STAT5a expression may be related to the ETV6-NTRK3 translocation. It was hypothesized that phosphorylated signal transducer and activator of transcription 5 (p-STAT5) might be specifically expressed in MASC of the salivary gland. The expression of p-STAT5 and mammaglobin (MMG) was examined with immunohistochemistry (IHC)/immunocytochemistry (ICC) in tissue sections from 58 salivary gland cancers (8 MASCs and 50 other salivary gland cancers) and in cytological smears from 17 salivary gland cancers (7 MASCs with paired histologic samples and 10 other salivary gland cancers). p-STAT5 IHC was clearly increased in MASC versus normal salivary gland tissue and other salivary gland cancers. p-STAT5 expression was found in 7 of 8 MASCs (87.5%) and in none of the 50 other salivary gland cancers (0%) by IHC. On cytology, p-STAT5 expression was found in all cases of MASC (7 of 7 or 100%) but in none of the 10 other salivary gland cancers (0%) by ICC. The expression rate of MMG by histology and cytology was higher than that of p-STAT5 in the other salivary gland cancers. p-STAT5 might be useful as a detection marker of MASC in the differential diagnosis of salivary gland cancers, and initial screening with p-STAT5 IHC/ICC, combined with auxiliary fluorescence in situ hybridization confirmation, is a reliable, economical approach to identifying MASC of the salivary gland. © 2015 American Cancer Society.

  17. Mammary analogue secretory carcinoma of salivary glands with high-grade transformation: report of 3 cases with the ETV6-NTRK3 gene fusion and analysis of TP53, β-catenin, EGFR, and CCND1 genes.

    Science.gov (United States)

    Skálová, Alena; Vanecek, Tomas; Majewska, Hanna; Laco, Jan; Grossmann, Petr; Simpson, Roderick H W; Hauer, Lukas; Andrle, Pavel; Hosticka, Lubor; Branžovský, Jindrich; Michal, Michal

    2014-01-01

    Mammary analogue secretory carcinoma of salivary gland origin (MASC) is a recently described tumor resembling secretory carcinoma of the breast characterized by strong S-100 protein, mammaglobin, and vimentin immunoexpression and which harbors a t(12;15) (p13;q25) translocation resulting in ETV6-NTRK3 fusion product. Histologically, conventional MASC displays bland histomorphology and a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogenous or bubbly secretions. Colloid-like secretory material stains positively for periodic acid-Schiff with and without diastase as well as for Alcian Blue. We present for the first time, 3 patients with MASC of the parotid gland in which high-grade (HG) transformation developed in each case characterized by an accelerated clinical course and poor outcome. The HG component revealed strong membrane staining for EGFR and β-catenin, cytoplasmic/nuclear staining for S-100 protein, and nuclear staining for cyclin-D1, whereas HER-2/neu was absent. Analysis for the presence of the ETV6-NTRK3 fusion transcript revealed positivity in both HG and low-grade component of MASC in 2 of the 3 studied cases. The tumor in case 2 was negative in both its elements for the t(12;15) translocation, but ETV6 gene rearrangement was detected in both components in all 3 cases. Analysis of TP53 and CTNNB1 gene mutations in the HG component of MASCs as well as detection of copy number aberration of EGFR and CCND1 gene did not harbor any abnormalities. All 3 patients with HG-transformed MASC died of disseminated disease within 2 to 6 years after diagnosis. Recognizing HG-transformed MASC and testing for ETV6 rearrangement may be of potential value in patient treatment, because the presence of the ETV6-NTRK3 translocation may represent a therapeutic target in MASC.

  18. Long-term cultivation of human mammary carcionoma: proliferation and differential biochemical properties of the cultured cells.

    Science.gov (United States)

    Hakim, A A

    1979-01-01

    Human mammary carcinoma cell cultures proliferated from primary explants in Eagle's essential medium (MEM) supplemented with insulin, fetal calf serum (FCS) and/or human alpha-a1-antitrypsin. Human mammary carcinoma cells differed from normal mammary epithelial cells by the following catalytic activities: a. Thymidine uptake into the carcinoma cells was 6 to 10 fold greater, whereas thymidine conversion to CO2 was half to one fifth that of normal cells. b. The nucleolytic activity patterns of the mammary carcinoma cells preferred polycytydylic acid and double helical polynucleotides, whereas those of the normal mammary cells preferred polyuridylic acid and had no effect on double helical polynucleotides. c. The polymerase activity most evident in mammary carcinoma cells is a hybrid-dependent DNA polymerase which is guided by the ribo-strand of the template poly (rA) . poly(dT). In contrast the all-ribo template poly (rA) . poly(rU) showed little activity. d. There was slight or statistically non-significant difference between the amino acid composition of material cleaved from mammary carcinoma cells prepared from tumor tissues and from cells cultivated 10 months in vitro. e. There was no difference between the molar proportions of the carbohydrate components of the cell membrane from fresh tumor tissue and long term in vitro cultivated cells. f. The granules from long term in vitro cultured mammary carcinoma cells contained high collagenolytic, caseinolytic, fibrinolytic and esterolytic activities.

  19. [Breast carcinoma metastasis into a renal cell carcinoma].

    Science.gov (United States)

    Perrin, Christophe; Talarmin, Marie; Fontaine, Aurélie; Kerbrat, Pierre; Audrain, Odile; Rioux-Leclercq, Nathalie; Chiforeanu, Dan Cristian

    2011-10-01

    We report the case of a patient carrying a right breast carcinoma whose imaging exams showed lung and bone metastasic release, and incidentally synchronous right renal tumor. Histologic examination of the renal tumor found a mammary carcinoma metastasis into a clear renal cell carcinoma. This is the second case report of breast cancer with metastasis in a resected renal clear cell carcinoma. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  20. Study of crotoxin mechanism of action to mammary carcinomas and evaluation of its potential as a radiopharmaceutical; Estudo do mecanismo de acao da crotoxina em tumores mamarios e avaliacao do seu potenctial radiofarmaceutico

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Marina Bicalho

    2010-07-01

    Crotoxin, the main component of Crotalus durissus terrificus snake venom, has been studied since 1938. It is a natural polypeptidic complex with pharmacological potential because of its antitumoral properties which has attracted great interest for diagnosis and therapy of oncological diseases. However, Crotoxin mechanism of action and sites of specific interaction on tumor cells are still misunderstood. Breast cancer is the second most frequent type in the world and the most common cancer in women. About 30 to 60% of mammary tumors overexpress epidermal growth factor receptor (EGFR), a transmembrane protein related to cell proliferation. Since literature has reported that Crotoxin antitumoral effect is more potent on cells with EGFR overexpression the objectives of this work were to evaluate Crotoxin cytotoxic effects on mammary tumor cells human breast carcinoma (MCF-7) and Ehrlich tumor cells (murine ascitics carcinoma), and to investigate the specific molecular interaction of Crotoxin on Ehrlich tumor cells. Initially, Crotoxin was radiolabelled with iodine-125 ({sup 125}I-Crotoxin) and iodine-131 ({sup 131}I-Crotoxin). Saturation and competition assay were carried out to characterize Crotoxin in vitro interaction; Crotoxin biodistribution studies and singlephoton emission computed tomography (SPECT) of mice bearing Ehrlich tumor have been evaluated to describe in vivo interaction. Our results showed that Crotoxin presented cytotoxic effect against Ehrlich with DL{sub 50} in vitro (concentration of compound which is lethal for 50% of cells) of about one micromolar, but did not present significant effect against MCF-7. Morphological alterations characteristic of apoptosis suggests programmed cell death. {sup 125}I-Crotoxin interaction with Ehrlich tumor cells was saturable with approximately 70% specificity, and presented K{sub d}=24.98 nmol/L and B{sub max}=16,570 sites/cell for low affinity binding sites and K{sub d}=0.06 nmol/L and B{sub max}=210 sites

  1. Mammary adenocarcinomas in three male cats exposed to medroxyprogesterone acetate (1990-2006).

    Science.gov (United States)

    Jacobs, Terry M; Hoppe, Bruce R; Poehlmann, Cathy E; Ferracone, Jackie D; Sorenmo, Karin U

    2010-02-01

    In this case series, three unrelated male housemate cats were treated repeatedly with injections of medroxyprogesterone acetate (MPA) for intercat aggression and urinary house soiling. All three cats subsequently developed multiple recurrent mammary adenocarcinomas and underwent numerous surgical resections. This report describes the clinical, histopathological and immunohistochemical findings in these three cats and highlights the potential for mammary carcinomas to develop in male cats years after receiving MPA injections. Extended survival times and a long delay between the administration of the progestin injections and the onset of mammary neoplasia are noted. Estrogen and progesterone receptor staining was performed on some of the tumors and the complex role of hormones in the pathogenesis and the prognosis of feline mammary carcinoma is discussed. Clinicians using MPA should institute life-long surveillance of their feline patients for mammary tumors. Copyright 2009 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

  2. Molecular pathology of breast apocrine carcinomas

    DEFF Research Database (Denmark)

    Celis, J.E.; Gromova, I.; Gromov, P.

    2006-01-01

    , specific antibodies against the components of the expression signature have identified precursor lesions in the linear histological progression to apocrine carcinoma. Finally, the identification of proteins that characterize the early stages of mammary apocrine differentiation such as 15-PGDH, HMG...

  3. Mammary Duct Ectasia

    Science.gov (United States)

    ... lumps Mammary duct ectasia Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  4. Characterization of the Six1 homeobox gene in normal mammary gland morphogenesis

    Directory of Open Access Journals (Sweden)

    McManaman James L

    2010-01-01

    Full Text Available Abstract Background The Six1 homeobox gene is highly expressed in the embryonic mammary gland, continues to be expressed in early postnatal mammary development, but is lost when the mammary gland differentiates during pregnancy. However, Six1 is re-expressed in breast cancers, suggesting that its re-instatement in the adult mammary gland may contribute to breast tumorigenesis via initiating a developmental process out of context. Indeed, recent studies demonstrate that Six1 overexpression in the adult mouse mammary gland is sufficient for initiating invasive carcinomas, and that its overexpression in xenograft models of mammary cancer leads to metastasis. These data demonstrate that Six1 is causally involved in both breast tumorigenesis and metastasis, thus raising the possibility that it may be a viable therapeutic target. However, because Six1 is highly expressed in the developing mammary gland, and because it has been implicated in the expansion of mammary stem cells, targeting Six1 as an anti-cancer therapy may have unwanted side effects in the breast. Results We sought to determine the role of Six1 in mammary development using two independent mouse models. To study the effect of Six1 loss in early mammary development when Six1 is normally expressed, Six1-/- embryonic mammary glands were transplanted into Rag1-/- mice. In addition, to determine whether Six1 downregulation is required during later stages of development to allow for proper differentiation, we overexpressed Six1 during adulthood using an inducible, mammary-specific transgenic mouse model. Morphogenesis of the mammary gland occurred normally in animals transplanted with Six1-/- embryonic mammary glands, likely through the redundant functions of other Six family members such as Six2 and Six4, whose expression was increased in response to Six1 loss. Surprisingly, inappropriate expression of Six1 in the adult mammary gland, when levels are normally low to absent, did not inhibit

  5. Coexistência de linfadenite axilar tuberculosa e metástase ganglionar de carcinoma lobular de mama: relato de um caso Coexistence of axillary tuberculous lymphadenitis and ganglionic metastasis in mammary lobular carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    José Juvenal Linhares

    2005-07-01

    Full Text Available Relato do caso de uma mulher com 83 anos apresentando nódulo e retração de pele na mama direita com oito meses de evolução. Ao exame físico verificou-se nódulo sólido de 5 cm, localizado no quadrante súpero-lateral de mama direita, associado a presença de retração de pele correspondente e linfonodos axilares não coalescentes ipsilaterais. O resultado da mamografia evidenciou nódulo de 4 cm de diâmetro irregular no quadrante súpero-lateral da mama direita (bi-rads V. Estádio clínico: T2N1M0 (IIB. O tratamento cirúrgico incluiu mastectomia radical modificada (à Maden com dissecção axilar níveis I, II e III. Avaliação histopatológica demonstrou a presença de carcinoma lobular infiltrativo que mediu 2,5 cm (T2, presença de linfadenite granulomatosa causada por tuberculose em linfonodos dos níveis I, II e III, associados a metástase de carcinoma lobular em um único nível linfático, nível I. Estádio patológico: pT2pN1aM0. A paciente recebeu tratamento para tuberculose ganglionar com rifampicina, isoniazida e pirazinamida por um ano. Foram solicitados receptores hormonais, os quais mostraram-se positivos, sendo feito terapia adjuvante com tamoxifeno. Durante o primeiro ano de seguimento a paciente evoluiu bem, sem sinais de recidiva local ou metástases a distância.Report of a case of an 83-year-old woman presenting a nodule and skin retraction in the right breast for eight months. On physical examination, a solid nodule of 5 cm was observed, located in the upper-lateral quadrant of the right breast, associated with skin retraction and ipsilateral lymph nodes. Mammographic findings showed irregularly limited nodules of 4 cm in the upper-lateral quadrant of the right breast (bi-rads V. Clinical staging: T2N1M0 (IIB. Surgical treatment included a modified radical mastectomy with axillary dissection levels I, II, and III. Histopathologic evaluation demonstrated the presence of an infiltrating lobular carcinoma

  6. Immunoglobins in mammary secretions

    DEFF Research Database (Denmark)

    Hurley, W L; Theil, Peter Kappel

    2013-01-01

    Immunoglobulins secreted in colostrum and milk by the lactating mammal are major factors providing immune protection to the newborn. Immunoglobulins in mammary secretions represent the cumulative immune response of the lactating animal to exposure to antigenic stimulation that occurs through...... interaction with the environment. Extensive species variability exists in how and when maternal immunoglobulins are transferred to the neonate. In addition, there is a range of mechanisms by which the transferred immunoglobulins may play a protective role in the neonate. This chapter reviews...... the immunoglobulins found in mammary secretions in the context of their diversity of structure, origin, mechanisms of transfer, and function....

  7. Ultrasound appearance of chronic mammary duct ectasia

    Energy Technology Data Exchange (ETDEWEB)

    Duchesne, N. [Ottawa Hospital, Dept. of Radiology, Ottawa, Ontario (Canada)]. E-mail: nathalie_duchesne_22@yahoo.ca; Skolnik, S. [Univ. of Toronto, Dept. of Family Medicine, Toronto, Ontario (Canada); Bilmer, S. [Ottawa Hospital, Dept. of Radiology, Ottawa, Ontario (Canada)

    2005-12-15

    Mammary duct ectasia (MDE), also called periductal mastitis, mammary dysplasia, or plasma cell mastitis, is a benign condition of the mammary gland first described by Haagensen in 1951. The etiology of MDE is unknown and its pathogenesis still controversial; the periductal inflammation could be either the cause or the result of dilated damaged ducts. The process is usually bilateral and asymptomatic, with only a small percentage of patients presenting with symptoms that may include long course of tumour formation, usually subareolar breast lumps, nipple discharge, nipple retraction, mastalgia, and mammary abscess or fistulas. Mammographic presentation of MDE is well known; its features include periductal calcification, benign intraductal calcification, and retroareolar duct dilatation. The periductal calcification results from dystrophic calcification and forms calcified rings or very dense, oval, elongated calcifications, each with a central lucency representing the dilated duct. Intraductal calcifications of duct ectasia represent inspissated intraductal material and are typically of uniform high density, often needle-like, and occasionally branching. Occasionally, there are no mammographic findings, and the diagnosis must rely on sonographic features. Appearance of MDE on ultrasonography (US) depends on the stage of the disease and the contents of the dilated ducts. The acute presentation has been demonstrated in the literature more often than has its chronic counterpart. In the former, duct content can vary from anechoic to isoechoic with surrounding fatty tissue. In chronic MDE, episodes of inflammation are longer. This tends to result in secretions that have a more solid, cheesy texture, partly due to cholesterol crystals, foam cells, and inflammatory cells. For both types of MDE, the appearance can mimic high-grade ductal carcinoma in situ (DCIS) on US. In this essay, 2 chronic MDE cases are presented and their US appearance discussed. Our goal is to explore

  8. Malignant mammary tumor in female dogs: environmental contaminants

    Directory of Open Access Journals (Sweden)

    Bissacot Denise Z

    2010-06-01

    Full Text Available Abstract 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.

  9. Carcinoma de células escamosas em glândula mamária de gata doméstica

    OpenAIRE

    Filgueira,Kilder Dantas; Reche Junior,Archivaldo

    2012-01-01

    Background: In the feline species, 80% to 93% of neoplasias in the mammary gland are malignant, being the majority carcinomas. Among them, there is the mammary squamous cell carcinoma, which amounts to a very rare neoplasm in the domestic cat, with considerable potential for malignancy. This study aimed to report a case of squamous cell mammary carcinoma in the feline species. Case: A female cat, mixed breed, ten years old, presented history of skin lesion. The cat had been spayed two years b...

  10. An Unusual Case of Mammary Paget’s Disease Diagnosed Using Dynamic Contrast-Enhanced MRI

    Directory of Open Access Journals (Sweden)

    Eleonora Gaspari

    2013-01-01

    Full Text Available Mammary Paget’s disease is a rare presentation of breast cancer. At clinical examination, it is characterized by skin lesions of the nipple-areola complex, almost always a sign of malignancy. In fact, it is often associated with an underlying mammary ductal carcinoma in situ (DCIS or invasive carcinoma. An underlying carcinoma is also common in women with negative mammography and ultrasound (US; in these cases, magnetic resonance imaging (MRI is a diagnostic tool useful in the detection of occult cancer. We described an unusual case of mammary Paget’s disease with underlying DCIS, in a patient without nipple-areola complex alterations and/or palpable lump. On suspicion of Paget’s disease, the patient underwent MRI examination that proved useful for an accurate diagnosis. Biopsy confirmed dynamic MRI findings.

  11. Primary Neuroendocrine Carcinoma of Breast: A Rare Case Report

    African Journals Online (AJOL)

    Department of Pathology, ESIC Medical College and PGIMSR, Rajajinagar, Bangalore, India. Abstract. Primary neuroendocrine carcinoma (PNEC) of breast was an unknown pathologic entity till recently due ... whole body computed tomography and magnetic resonance imaging revealed no extra mammary primary tumor.

  12. Humanization of the mouse mammary gland.

    Science.gov (United States)

    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.

  13. Comparative pathology of mammary gland cancers in domestic and wild animals.

    Science.gov (United States)

    Munson, Linda; Moresco, Anneke

    2007-01-01

    Mammary cancer occurs among all taxonomic groups, and comparing the disease in animals with breast cancer in women could greatly improve our understanding of the relevant risk factors and genetic profiles for this disease. Differences in cancer prevalence between carnivores and herbivores and between captive and wild carnivores are striking and support the hypotheses that diet and reproductive history are major risk factors. Domestic dogs and cats have a high prevalence of mammary tumors, and the majority of tumors in cats are aggressive cancers. Many domestic dogs and cats are prevented from breeding, resulting in their being exposed to recurrent estrogen peaks followed by high persistent levels of progesterone. Therefore progesterone appears to be a significant risk factor for cancer development. Supporting this suspicion is the observation that most mammary cancers in zoo cats are in those treated with the potent synthetic progestin contraceptive, melengestrol acetate. The more common morphologic types of mammary cancer in canids and felids include tubulopapillary, solid, cribriform, comedo and anaplastic carcinomas. Dogs also develop complex carcinomas, which likely evolve from the complex adenomas or mixed tumors that are so common in this species and are promoted by exogenous progesterone treatment. Among zoo felids, jaguars are at higher risk for mammary cancer and also have a high prevalence of ovarian papillarycystadenocarcinomas, a profile similar to women with BRCA1 mutations. As for women, estrogen (ER) and progesterone receptor (PR) expression varies in canine and feline mammary cancers. In general, ER expression is low, but PR expression persists in most cancers. Alterations in molecular controls of cell proliferation or survival in breast cancer, such as cyclin A and p53 expression, have been identified in dog and cat mammary cancers. Overall, spontaneous mammary cancers in cats and dogs make excellent models for human breast cancer, and knowledge of

  14. Kinetics of mammary clonogenic cells and rat mammary cancer induction by X-rays or fission neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Kamiya, Kenji [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine; Higgins, P.D.; Tanner, M.A.; Gould, M.N.; Clifton, K.H.

    1999-12-01

    Following the hormonal treatment of rats with high prolactin levels and glucocorticoid deficiency (Prl+/Glc-) for 48 days (Day +48), total recoverable mammary DNA was increased by more than sevenfold, tritiated thymidine uptake by nearly fourfold, and total mammary clonogens by about fivefold. Irradiation with 4, 40, and 80 cGy X-rays on Day +48 increased total mammary carcinomas per rat-day-at-risk linearly with dose, and 40 and 80 cGy significantly decreased first carcinoma latency. A dose of 40 cGy X-rays before hormone treatment (Day -1) yielded tumor latencies and frequencies insignificantly different from unirradiated controls but significantly different from those when the dose was given on Day +48. Total carcinomas per rat-day-at-risk were fitted better by a function of dose to the power 0.4 than by a linear function after exposure to 1, 10. and 20 cGy fission neutrons, and 10 and 20 cGy significantly shortened the time to appearance of the first cancer. In contrast to results with X-rays, 10 cGy neutrons on Day -1 yielded tumor frequencies and latencies insignificantly different from 10 cGy neutrons on Day +48. The carcinogenic action of X-rays, but not of neutrons, was thus influenced by total clonogen numbers and/or proliferation rates. (author)

  15. Hormone-sensing cells require Wip1 for paracrine stimulation in normal and premalignant mammary epithelium.

    Science.gov (United States)

    Tarulli, Gerard A; De Silva, Duvini; Ho, Victor; Kunasegaran, Kamini; Ghosh, Kakaly; Tan, Bryan C; Bulavin, Dmitry V; Pietersen, Alexandra M

    2013-01-31

    The molecular circuitry of different cell types dictates their normal function as well as their response to oncogene activation. For instance, mice lacking the Wip1 phosphatase (also known as PPM1D; protein phosphatase magnesium-dependent 1D) have a delay in HER2/neu (human epidermal growth factor 2), but not Wnt1-induced mammary tumor formation. This suggests a cell type-specific reliance on Wip1 for tumorigenesis, because alveolar progenitor cells are the likely target for transformation in the MMTV(mouse mammary tumor virus)-neu but not MMTV-wnt1 breast cancer model. In this study, we used the Wip1-knockout mouse to identify the cell types that are dependent on Wip1 expression and therefore may be involved in the early stages of HER2/neu-induced tumorigenesis. We found that alveolar development during pregnancy was reduced in Wip1-knockout mice; however, this was not attributable to changes in alveolar cells themselves. Unexpectedly, Wip1 allows steroid hormone-receptor-positive cells but not alveolar progenitors to activate STAT5 (signal transducer and activator of transcription 5) in the virgin state. In the absence of Wip1, hormone-receptor-positive cells have significantly reduced transcription of RANKL (receptor activator of nuclear factor kappa-B ligand) and IGF2 (insulin-like growth factor 2), paracrine stimulators of alveolar development. In the MMTV-neu model, HER2/neu activates STAT5 in alveolar progenitor cells independent of Wip1, but HER2/neu does not override the defect in STAT5 activation in Wip1-deficient hormone-sensing cells, and paracrine stimulation remains attenuated. Moreover, ERK (extracellular signal-regulated kinase) activation by HER2/neu in hormone-sensing cells is also Wip1 dependent. We identified Wip1 as a potentiator of prolactin and HER2/neu signaling strictly in the molecular context of hormone-sensing cells. Furthermore, our findings highlight that hormone-sensing cells convert not only estrogen and progesterone but also

  16. Clinicopathologic evaluation of mammary Paget′s disease

    Directory of Open Access Journals (Sweden)

    Meibodi Naser

    2008-01-01

    Full Text Available Mammary and extramammary Paget′s diseases are rare neoplasms of epidermis and mucosal epithelium. Due to their nonspecific and variable clinical view, they have differential diagnosis with eczema, melanoma, Bowen′s disease, etc. To the best of our knowledge, no such study has been performed in Iran regarding the prevalence, clinical aspects, underlying disease and pathological characteristics of these two diseases. In this study, we have evaluated the clinical and histopathological aspects of this disorder. Materials and Methods: In this retrospective study, all Paget′s biopsied samples referred to the Pathology Department of Imam-Reza hospital, Mashhad, since 1984 till 2004 were evaluated. Collected data were analyzed by descriptive statistical methods. Results: Among 98925 specimens, there were 29 cases of Paget′s disease. All cases were married women suffering from mammary Paget. The mean age was 53 ± 11 years. Left and right breast involvement was observed in 17 and 12 cases, all unilateral. The most common clinical view was ulcerated (27% and then erythematosus exudative plaques. More than 50% of patients were symptomatic. Most common symptoms were itching, pain and burning. The exclusive underlying pathological diagnosis was ductal carcinoma (55%. Discussion: In most cases, the clinical view of mammary Paget′s disease was helpful. Unilateral ulcerated plaque was the most common clinical sign. Majority of the accompanying pathology was ductal carcinoma. We had no cases of extramammary Paget′s disease in our study.

  17. Mammary tuberculosis: percutaneous treatment of a mammary tuberculous abscess

    Energy Technology Data Exchange (ETDEWEB)

    Romero, C.; Carreira, C.; Cereceda, C.; Pinto, J. [Servicio de Radiologia, Hospital Virgen de la Salud, Toledo (Spain); Lopez, R.; Bolanos, F. [Servicio de Cirugia, Hospital Virgen de la Salud, Toledo (Spain)

    2000-03-01

    It is currently very rare to find mammary involvement in cases of tuberculosis, in either primary or secondary form. Diagnosis is classically clinical and microbiological, and the basic techniques used in imaging diagnosis are mammography and ultrasound. Computed tomography may define the involvement of the thoracic wall in those cases which present as mammary masses adhering to deep levels, and is also able to evaluate accompanying pulmonary disease, if it is present. Traditionally, treatment has consisted of quadrantectomy and specific antibiotic therapy. We present a case of tuberculous mammary abscess secondary to pulmonary disease, which was treated by percutaneous drainage controlled by CT and specific antibiotic therapy. We revise the diagnosis, differential diagnosis and treatment of mammary tuberculosis. (orig.)

  18. Establishment of primary mixed cell cultures from spontaneous canine mammary tumors: Characterization of classic and new cancer-associated molecules

    Science.gov (United States)

    Gentile, Luciana B.; Nagamine, Marcia K.; Biondi, Luiz R.; Sanches, Daniel S.; Toyota, Fábio; Giovani, Tatiane M.; de Jesus, Isis P.; da Fonseca, Ivone I. M.; Queiroz-Hazarbassanov, Nicolle; Diaz, Bruno L.; Salles Gomes, Cristina de O. Massoco

    2017-01-01

    There are many factors which make canine cancer like cancer in humans. The occurrence of spontaneous mammary tumors in pet dogs, tumor genetics, molecular targets and exposure to the same environmental risk factors are among these factors. Therefore, the study of canine cancer can provide useful information to the oncology field. This study aimed to establish and characterize a panel of primary mixed cell cultures obtained from spontaneous canine mammary tumors. Eight established cell cultures obtained from one normal mammary gland, one complex adenoma, one mixed adenoma, two complex carcinomas and two mixed carcinomas were analyzed. The gene expression levels of classic molecular cancer players such as fibroblast growth factor receptor (FGFR) 2, breast cancer (BRCA) 1, BRCA2 and estrogen receptor (ESR) 1 were evaluated. For the first time, three orphan nuclear receptors, estrogen-related receptors (ERRs) α, β and γ were studied in canine mammary cancer. The highest expression level of ERRα was observed in complex carcinoma-derived cell culture, while the highest levels of ERRβ and γ were observed in cells derived from a mixed carcinoma. Meanwhile, complex carcinomas presented the highest levels of expression of ESR1, BRCA1 and FGFR2 among all samples. BRCA2 was found exclusively in complex adenoma. The transcription factor GATA3 had its highest levels in mixed carcinoma samples and its lowest levels in complex adenoma. Proliferation assays were also performed to evaluate the mixed cell cultures response to ER ligands, genistein and DES, both in normoxia and hypoxic conditions. Our results demonstrate that morphological and functional studies of primary mixed cell cultures derived from spontaneous canine mammary tumors are possible and provide valuable tool for the study of various stages of mammary cancer development. PMID:28945747

  19. Lesions of anogenital mammary-like glands: an update.

    Science.gov (United States)

    Kazakov, Dmitry V; Spagnolo, Dominic V; Kacerovska, Denisa; Michal, Michal

    2011-01-01

    Long considered to be ectopic breast tissue representing the caudal remnants of the milk ridges, anogenital mammary-like glands are nowadays thought to represent a normal constituent of the anogenital area. Lesions involving these glands, benign or malignant, epithelial or stromal manifest a striking similarity to their mammary counterparts. This review addresses the recent literature on lesions of anogenital mammary-like glands and our personal experience with various lesions related to these structures. Discussed are the normal anatomy and histology of these glands as well as the clinical presentation, histopathological and immunohistochemical features, molecular biological aspects, and differential diagnosis of various lesions involving anogenital mammary-like glands, including lactating adenoma, hidradenoma papilliferum, hidradenocarcinoma papilliferum, fibroadenomas, phyllodes tumor, pseudoangiomatous stromal hyperplasia, extramammary Paget disease, and other carcinomas. In addition, "nonspecific" epithelial or stromal changes some of which can be likened to similar changes occurring in a range of benign breast disease, including sclerosing adenosis, columnar cell lesions, ductal lesions and various metaplastic changes affecting epithelium and myoepithelium are discussed. Although lesions of anogenital mammary-like glands are often discussed in many dermatopathology textbooks in the context of cutaneous adnexal neoplasms we advocate that the best approach to the diagnosis of these lesions is to relate them to analogous well recognized lesions occurring in the breast, that is, through the eyes of a breast pathologist. This will enable their recognition, precise classification and should introduce greater uniformity in how they are reported in the literature so that more meaningful clinicopathological comparisons and correlations may be made.

  20. Canine mammary tumors - clinical survey

    Directory of Open Access Journals (Sweden)

    Elena Atanaskova Petrov

    2014-10-01

    Full Text Available Mammary tumours are the second most frequent neoplasia in dogs, mainly affecting older female patients. Approximately 50% of the mammary tumours are malignant with high percentage of mortality if not treated in time. The aim of this study was to analyze the data of canine patients with mammary tumours, to evaluate the type of tumours, as well as the relationship between tumour incidence and dogs’ age, reproductive cycle and sterilization. The survey was used to retrieve the information in the period of two years from the patient data base of the University Veterinary Hospital at the Faculty of Veterinary medicine in Skopje. Patients included in this survey were subjected to routine clinical investigation and additional laboratory tests (cytological examination, x-rays imaging, CBC and biochemical profile, histopathology of the tumor samples. Aged female patients (12 – 13 years are the most susceptible category for development of mammary tumours. The reproductive history showed that five of the patients with malignant mammary tumourshave never whelped and were not treated with any exogenous hormones. Malignant tumours (adenocarcinoma were diagnosed in 90% of the patients. Three patients died due to lung metastasis. Late diagnosis is one of the major problems that results in lethal outcome due to lung metastases. Since ovarian steroids play an important role in the aetiology, the most effective prevention of mammary tumoursis elective ovariectomy of the bitch at an early age.

  1. Mammary scintigraphy; Cintilografia mamaria

    Energy Technology Data Exchange (ETDEWEB)

    Mello, Gustavo Lanza de; Christo, Rodrigo Campos; Paz, Wagner A.; Paim, Soraya P.; Rangel, Kerstim K.; Barroso, Adelanir A.; Lima, Carla Flavia de [Hospital Luxemburgo, Belo Horizonte, MG (Brazil)

    2000-09-01

    The early detection of breast cancer using mammography as screening method lowered 30% breast carcinoma mortality in women over 50 years and also, allowing conservative procedures. Mammography sensitivity has limitations in younger patients with dense fibroglandular tissue. Scintimammography is suitable as a complementary method to mammography in patients with dense breasts, but has low sensitivity in lesion minor than one centimeter in diameter. (author)

  2. Expression of NOS and VEGF in feline mammary tumours and their correlation with angiogenesis.

    Science.gov (United States)

    Islam, M S; Matsumoto, M; Hidaka, R; Miyoshi, N; Yasuda, N

    2012-06-01

    In order to define the role of nitric oxide (NO) in feline mammary tumours, the expression of endothelial or inducible nitric oxide synthase (e/iNOS) and vascular endothelial growth factor (VEGF), and their relationship with angiogenesis, was investigated in 23 feline mammary tumours (two hyperplastic, 19 adenocarcinoma, one osteosarcoma and one squamous cell carcinoma) by immunohistochemistry. Tumour angiogenesis was assessed by CD31 immunostaining and was expressed as microvessel density (MVD). In general, iNOS immunoreactivity was localised in tumour cells and occasionally in stromal myofibroblasts, whereas eNOS and VEGF were localised in the cytoplasm of tumour epithelial cells and endothelium. In malignancy, expression of iNOS increased from well- to less-differentiated phenotypes (Grades 1-3) and was significantly higher in G3 and G2 when compared with G1 cases. However, increasing eNOS expression was limited only in hyperplastic lesions and showed no significant changes among the grades. In addition, expression of iNOS was positively correlated with VEGF and MVD in feline mammary tumours and both measures were significantly greater in less differentiated phenotypes (Pfeline mammary tumours depended on tumour grade, and the positive correlations between iNOS and angiogenic markers suggests that iNOS synthesised by tumour cells promotes tumour growth. Thus, iNOS can be used as an important immunohistochemical marker to determine the degree of malignancy and prognosis of feline mammary carcinoma. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. An Immunohistochemical study of HER-2 expression in feline mammary tumours.

    Science.gov (United States)

    Rasotto, R; Caliari, D; Castagnaro, M; Zanetti, R; Zappulli, V

    2011-01-01

    The aim of the present study was to evaluate HER-2 expression in feline mammary tumours. Five different immunohistochemical protocols were tested with 73 feline mammary carcinomas (MCs), 10 mammary adenomas and 73 hyperplastic or dysplastic mammary lesions. The histological features of these lesions, clinical follow-up and expression of Ki-67 and p53 were also examined. With an optimized immunohistochemical protocol, HER-2 overexpression was detected in only four of the 73 (5.5%) MCs and did not correlate with histological classification or with the 1 year post-surgical clinical outcome. No correlation was found between the expression of Ki-67 or p53 and HER-2. Five of the 73 (6.8%) hyperplastic or dysplastic lesions and one of the 10 (10%) mammary adenomas were HER-2 positive. These results suggest that HER-2 may not play as significant role in mammary carcinogenesis and prognosis in cats as it does in human patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Cell surface heparan sulfate proteoglycans control adhesion and invasion of breast carcinoma cells

    DEFF Research Database (Denmark)

    Lim, Hooi Ching; Multhaupt, Hinke A. B.; Couchman, John R.

    2015-01-01

    phenotype of mammary carcinoma cells. Finally, both syndecan-2 and caveolin-2 were upregulated in tissue arrays from breast cancer patients compared to normal mammary tissue. Moreover their expression levels were correlated in triple negative breast cancers. Conclusion: Cell surface proteoglycans, notably...

  5. Evaluation of serum haptoglobin and C-reactive protein in dogs with mammary tumors.

    Science.gov (United States)

    Planellas, Marta; Bassols, Anna; Siracusa, Carlo; Saco, Yolanda; Giménez, Mercè; Pato, Raquel; Pastor, Josep

    2009-09-01

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

  6. Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue.

    Science.gov (United States)

    Volden, Paul A; Wonder, Erin L; Skor, Maxwell N; Carmean, Christopher M; Patel, Feenalie N; Ye, Honggang; Kocherginsky, Masha; McClintock, Martha K; Brady, Matthew J; Conzen, Suzanne D

    2013-07-01

    Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen FVB/N (TAg) mouse model of "triple-negative" breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e., during the in situ carcinoma stage). To further understand the mechanisms underlying how accelerated mammary tumor growth is associated with social isolation, we separated the mammary gland adipose tissue from adjacent ductal epithelial cells and analyzed individual cell types for changes in metabolic gene expression. Specifically, increased expression of the key metabolic genes Acaca, Hk2, and Acly was found in the adipocyte, rather than the epithelial fraction. Surprisingly, metabolic gene expression was not significantly increased in visceral adipose depots of socially isolated female mice. As expected, increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and leptin secretion from this adipose depot. Furthermore, application of media that had been cultured with isolated mouse mammary adipose tissue (conditioned media) resulted in increased proliferation of mammary cancer cells relative to group-housed-conditioned media. These results suggest that exposure to a chronic stressor (social isolation) results in specific metabolic reprogramming in mammary gland adipocytes that in turn contributes to increased proliferation of adjacent preinvasive malignant epithelial cells. Metabolites and/or tumor growth-promoting proteins secreted from adipose tissue could identify biomarkers and/or targets for preventive intervention in breast cancer. ©2013 AACR.

  7. Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue

    Science.gov (United States)

    Volden, Paul A.; Wonder, Erin L.; Skor, Maxwell N.; Carmean, Christopher M.; Patel, Feenalie N.; Ye, Honggang; Kocherginsky, Masha; McClintock, Martha K.; Brady, Matthew J.; Conzen, Suzanne D.

    2013-01-01

    Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen FVB/N (TAg) mouse model of “triple-negative” breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e. during the in situ carcinoma stage). To further understand the mechanisms underlying how accelerated mammary tumor growth is associated with social isolation, we separated the mammary gland adipose tissue from adjacent ductal epithelial cells and analyzed individual cell types for changes in metabolic gene expression. Specifically, increased expression of the key metabolic genes Acaca, Hk2 and Acly was found in the adipocyte, rather than the epithelial fraction. Surprisingly, metabolic gene expression was not significantly increased in visceral adipose depots of socially isolated female mice. As expected, increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and leptin secretion from this adipose depot. Furthermore, application of media that had been cultured with isolated mouse mammary adipose tissue (conditioned media) resulted in increased proliferation of mammary cancer cells relative to group-housed conditioned media. These results suggest that exposure to a chronic stressor (social isolation) results in specific metabolic reprogramming in mammary gland adipocytes that in turn contributes to increased proliferation of adjacent pre-invasive malignant epithelial cells. Metabolites and/or tumor growth-promoting proteins secreted from adipose tissue could identify biomarkers and/or targets for preventive intervention in breast cancer. PMID:23780289

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Lisa Y., E-mail: lisa.pang@ed.ac.uk; Cervantes-Arias, Alejandro; Else, Rod W.; Argyle, David J. [Royal (Dick) School of Veterinary Studies and Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG (United Kingdom)

    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.

  10. Mammary Analogue Secretory Carcinoma of Salivary Glands: Molecular Analysis of 25 ETV6 Gene Rearranged Tumors With Lack of Detection of Classical ETV6-NTRK3 Fusion Transcript by Standard RT-PCR: Report of 4 Cases Harboring ETV6-X Gene Fusion.

    Science.gov (United States)

    Skálová, Alena; Vanecek, Tomas; Simpson, Roderick H W; Laco, Jan; Majewska, Hanna; Baneckova, Martina; Steiner, Petr; Michal, Michal

    2016-01-01

    ETV6 gene abnormalities are well described in tumor pathology. Many fusion partners of ETV6 have been reported in a variety of epithelial and hematological malignancies. In salivary gland tumor pathology, however, the ETV6-NTRK3 translocation is specific for mammary analogue secretory carcinoma (MASC), and has not been documented in any other salivary tumor type. The present study comprised a clinical and molecular analysis of 25 cases morphologically and immunohistochemically typical of MASC. They all also displayed the ETV6 rearrangement as visualized by fluorescent in situ hybridization but lacked the classical ETV6-NTRK3 fusion transcript by standard reverse-transcriptase-polymerase chain reaction. In 4 cases, the classical fusion transcript was found by more sensitive, nested reverse-transcription-polymerase chain reaction. Five other cases harbored atypical fusion transcripts as detected by both standard and nested reverse-transcription-polymerase chain reaction. In addition, fluorescent in situ hybridization with an NTRK3 break-apart probe was also performed; rearrangement of NTRK3 gene was detected in 16 of 25 cases. In 3 other cases, the tissue was not analyzable, and in 2 further cases analysis could not be performed because of a lack of appropriate tissue material. Finally, in the 4 remaining cases whose profile was NTRK3 split-negative and ETV6 split-positive, unknown (non-NTRK) genes appeared to fuse with ETV6 (ETV6-X fusion). In looking for possible fusion partners, analysis of rearrangement of other kinase genes known to fuse with ETV6 was also performed, but without positive results. Although numbers were small, correlating the clinico-pathologic features of the 4 ETV6-X fusion tumors and 5 MASC cases with atypical fusion transcripts raises the possibility of that they may behave more aggressively.

  11. The mammary gland and the homeobox gene Otx1.

    Science.gov (United States)

    Pagani, Ilaria S; Terrinoni, Alessandro; Marenghi, Laura; Zucchi, Ileana; Chiaravalli, Anna M; Serra, Valeria; Rovera, Francesca; Sirchia, Silvia; Dionigi, Gianlorenzo; Miozzo, Monica; Mozzo, Monica; Frattini, Annalisa; Ferrari, Alberta; Capella, Carlo; Pasquali, Francesco; Lo Curto, Francesco; Curto, Francesco L; Albertini, Alberto; Melino, Gerry; Porta, Giovanni

    2010-01-01

    The mammary gland, the unique organ that primarily form at puberty, is an ideal model to study the functions of homeobox (HB) genes in both development and tumorigenesis. HB genes comprise a large family of developmental regulators that have a critical role in cell growth and differentiation. In the normal mammary gland, homeobox genes are involved in ductal formation, epithelial branching, and lobulo-alveolar development by regulating epithelial proliferation and differentiation. The HB genes are controlled in a spatial and temporal manner in both stromal and epithelial cells. They are coordinately regulated by hormones and extracellular matrix, suggesting that many signaling pathways are involved in homeobox gene functions. When homeobox genes are misexpressed in animal models, different defects are displayed in mammary gland development. Aberrant expression of homeobox genes, overexpressed or downregulated, is found in primary carcinomas and in breast cancer. The Otx1 HB gene is a classic regulatory of nervous system development during embryogenesis. Postnatally Otx1 is transcribed in the anterior pituitary gland, where activates transcription of the pituitary hormones, and plays a role in hematopoiesis, enhancing pluripotent cells, and erythroid differentiation. Otx1 can still be detected in mature cells of the erythroid and megacaryocytic lineage. During cyclical development of mammary gland, the Otx1 gene is overexpressed in lactation, confirming a role of this transcription factor in cell differentiation. Recent studies report that Otx1 is overexpressed in breast cancer. Otx1 is expressed during embryogenesis, and it is expressed again during carcinogenesis, implying its possible function in differentiation of neoplastic cells. © 2010 Wiley Periodicals, Inc.

  12. Proposed classification of the feline "complex" mammary tumors as ductal and intraductal papillary mammary tumors.

    Science.gov (United States)

    Zappulli, V; Caliari, D; Rasotto, R; Ferro, S; Castagnaro, M; Goldschmidt, M

    2013-11-01

    When compared with the canine species, feline mammary tumors (FMTs) are much less heterogeneous, with a predominance of simple malignant neoplasm. Benign FMTs are rare, and it is unclear if complex and mixed tumors exist in the feline. In this study, we selected for immunohistochemical analyses 12 FMTs that had unusual histologic features. A group of 8 (2 benign and 6 malignant) FMTs showed a biphasic epithelial/myoepithelial population and a very regular cord-like distribution in a "Chinese lettering" pattern, within ectatic ducts. A second group (2 benign and 2 malignant) had an intraductal epithelial papillary growth pattern with a basally located monolayer of myoepithelial cells and a supporting fibrovascular stroma. The myoepithelial component always produced a standard immunohistochemical signature. All malignancies were grade I, and the subjects were all alive at 1 year postdiagnosis. On the basis of their morphology, we propose that they be classified as feline ductal adenoma/carcinoma and feline intraductal papillary adenoma/carcinoma, respectively. They overlap with their canine counterparts and lack the typical myoepithelial differentiation patterns seen in canine complex neoplasms, and therefore, the term complex should be avoided in felines. This study will add new information on FMT classification and be useful for prognostic studies.

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

    Directory of Open Access Journals (Sweden)

    Cassali Geovanni D

    2010-02-01

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

  14. Immunohistochemical detection of tumour cell proliferation and intratumoural microvessel density in canine malignant mammary tumours

    Directory of Open Access Journals (Sweden)

    Sennazli Gulbin

    2015-06-01

    Full Text Available The objective of this study was to investigate the correlation between different histological types and grades of canine malignant mammary tumours, tumour cell proliferation and their angiogenic activity using immunohistochemical markers. Mammary tissue samples from 47 bitches with mammary cancer were evaluated. The expression of cellular proliferation marker Ki-67 and endothelial marker Von Willebrand’s factor (vWF were immunohistochemically demonstrated. The tumours with the highest Ki-67 and vWF expressions were found to share similar histomorphological features. Simple solid carcinoma had the highest levels of Ki-67, vWF, and higher histological grade while complex carcinomas, osteosarcomas, and carcinosarcomas had the lowest ones. The differences between the expressions of Ki-67 and vWF in different tumour types were considered to be of great importance in determination of biological behaviour and prognosis of these tumours. This study is one of the few studies that evaluate these differences among the subtypes of malignant canine mammary tumours

  15. Axillary node metastasis from primary ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Trupti S Patel

    2014-01-01

    Full Text Available Metastasization and distinction from mammary carcinoma is of great clinical importance because of different treatment modalities. Here, we discuss a case of stage IIIC ovarian serous carcinoma, presenting with bilateral axillary nodes metastasis after 25 months interval of its initial presentation. Increased serum CA-125 level caused clinical suspicion. Computed tomography scan of abdomen and pelvis showed no residual disease or any abdominal lymphadenopathy. Mammography of both breast were normal. Bilateral axillary nodes were noted. Guided fine needle aspiration cytology (FNAC and biopsy of ovarian carcinoma to axillary node is a rare event. Its recogn done. Cytomorphology revealed poorly differentiated carcinoma, compatible to that of primary ovarian tumor. Thus, metastatic carcinoma to axillary node from ovary was confirmed. This case illustrates a rare metastatic presentation of ovarian carcinoma and unequivocal role of FNAC to provide rapid diagnosis and preferred to be first line diagnostic procedure.

  16. Classification and Epidemiology of Mammary Tumours in Pet Rabbits (Oryctolagus cuniculus).

    Science.gov (United States)

    Baum, B; Hewicker-Trautwein, M

    2015-05-01

    Mammary tumours are common in pet rabbits; however, published studies are predominantly derived from laboratory and meat rabbits. This study reports basic data on type and location of 119 separate tumours from 109 pet rabbits. The animals were aged 2-14 years (mean 5.5 years) and all 90 rabbits of known gender were female. Cranial and caudal mammary glands were affected equally. The majority of lesions (n = 105) were classified as carcinomas with 32 tubular, 16 papillary, 12 tubulopapillary, 11 solid, nine adenosquamous, nine comedo type, five complex, four ductal, three cribriform, three anaplastic and one spindle -cell carcinoma. Twelve percent of the lesions were benign, with eight intraductal papillary adenomas, three simple tubular adenomas and one complex adenoma. One non-neoplastic lesion was found in the form of cystic duct ectasia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Ectopic mammary tissue in vulva

    Directory of Open Access Journals (Sweden)

    Đorđević Momčilo

    2008-01-01

    Full Text Available Background. Ectopic mammary gland tissue is a residual tissue that persists during the embryologic development along ectodermal primitive milk streaks. Incomplete involution anywhere along the primitive milk streak can result in accessory or ectopic mammary tissue. Case report. A woman, 27-year old, admitted to Obstetrics and Gynecology Clinic Kragujevac for surgery, of goose-egg size, vulva tumor, of elastic consistency. Menarche started in 12 years of age, with the regular menstrual cycle, without previous gynecological diseases. The woman had one pregnancy terminated by cesarean section because of the multiple (twin pregnancy. Excision of the tumor was completely done in the total endotracheal anesthesia. Pathohistologic (PH findings was: Dysplasia fibrosa cystica simplex mammae, with focuses of sclerosing adenosis. Expression of estrogen (ER and progesterone receptors (PR were positive. Conclusion. Ectopic mammary tissue in vulva in adult period is very rarely seen, and can be changed pathologically as well as normally positioned breast tissue into benign cystic changes, benign tumors, adenomas and fibroadenomas and tumors. Cells with low ER/PR receptor level grow independently of estrogene stimulation and they could be resistant to hormonal therapy effects.

  18. Evolution of somatic mutations in mammary tumors in transgenic mice is influenced by the inherited genotype

    Directory of Open Access Journals (Sweden)

    Li Yi

    2004-06-01

    Full Text Available Abstract Background MMTV-Wnt1 transgenic mice develop mammary hyperplasia early in development, followed by the appearance of solitary mammary tumors with a high proportion of cells expressing early lineage markers and many myoepithelial cells. The occurrence of tumors is accelerated in experiments that activate FGF proto-oncogenes or remove the tumor suppressor genes Pten or P53, implying that secondary oncogenic events are required for progression from mammary hyperplasia to carcinoma. It is not known, however, which oncogenic pathways contribute to Wnt1-induced tumorigenesis – further experimental manipulation of these mice is needed. Secondary events also appear to be required for mammary tumorigenesis in MMTV-Neu transgenic mice because the transgene in the tumors usually contains an acquired mutation that activates the Neu protein-tyrosine kinase. Methods cDNA or DNA from the mammary glands and mammary tumors from MMTV-Wnt1, MMTV-Wnt1/p53-/-, MMTV-Neu transgenic mice, and newly generated MMTV-Wnt1/MMTV-Neu bitransgenic mice, was sequenced to seek activating mutations in H-Ras, K-Ras, and N-Ras genes, or in the MMTV-Neu transgene. In addition, tumors from bitransgenic animals were examined to determine the cellular phenotype. Results We found activating mutations at codons 12, 13, and 61 of H-Ras in just over half of the mammary tumors in MMTV-Wnt1 transgenic mice, and we confirmed the high frequency of activating mutations of Neu in tumors in MMTV-Neu transgenic mice. Tumors appeared earlier in bitransgenic MMTV-Wnt1/MMTV-Neu mice, but no Ras or MMTV-Neu mutations were found in these tumors, which were phenotypically similar to those arising in MMTV-Wnt1 mice. In addition, no Ras mutations were found in the mammary tumors that arise in MMTV-Wnt1 transgenic mice lacking an intact P53 gene. Conclusions Tumorigenic properties of cells undergoing functionally significant secondary mutations in H-Ras or the MMTV-Neu transgene allow selection

  19. Ligand-independent canonical Wnt activity in canine mammary tumor cell lines associated with aberrant LEF1 expression.

    Directory of Open Access Journals (Sweden)

    Ana Gracanin

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Yaritza Salas

    Full Text Available 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. H-ras oncogene mutations during development of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced rat mammary gland cancer.

    Science.gov (United States)

    Yu, Minshu; Snyderwine, Elizabeth G

    2002-12-01

    Laser capture microdissection, polymerase chain reaction-restriction fragment length polymorphism analysis, and DNA sequencing was used to detect H-ras codon 12 and 13 mutations during the stages of mammary gland cancer development in rats exposed to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen found in cooked meat. Ten oral doses of PhIP (75 mg/kg, p.o., once per day) were administered to adolescent female Sprague-Dawley rats and mammary glands examined histologically for intraductal proliferations (IDPs), carcinoma in situ and carcinomas 7-14 weeks later. Mammary gland epithelial cells from normal tissue and distinct lesions were collected from glass slides and analyzed for mutations. H-ras codon 12/13 mutations were detected in 73%, 75%, 100%, and 100% of normal mammary glands, IDPs, carcinoma in situ, and carcinoma, respectively, after PhIP treatment. The spectrum of activating mutations included G(35) to A or C base substitution mutations in codon 12, and G(37) to T or A base substitution mutations in codon 13. The spectrum of H-ras mutations was similar among normal mammary gland from PhIP treated rats, preneoplastic lesions, and carcinomas. Furthermore, the spectrum of mutations was consistent with the involvement of PhIP-guanine adduct formation. The results support the notion that mutations in H-ras codons 12 and 13 are largely PhIP-DNA adduct-induced and involved in the initiation and development of mammary gland cancer in rats exposed to PhIP.

  2. Squamous cell carcinoma of the breast tissue: a case report

    OpenAIRE

    Rubens José Pereira; Wilson Garcia Pereira; Luiz Fernando Jubé Ribeiro; Rita de Cássia Alencar; Vera Saddi; Geraldo Silva Queiroz; Ruffo Freitas Júnior

    1999-01-01

    O carcinoma espinocelular do parênquima mamário é um tipo raro de neoplasia, representando menos de 1% de todos os carcinomas mamários. Esse trabalho relata a condução de um caso diagnosticado e tratado no Serviço de Ginecologia e Mama do Hospital Araújo Jorge/ACCG. São discutidos a apresentação clínica, o diagnóstico e o prognóstico destes tumores.Squamous cell carcinoma of the mammary tissue is a very rare neoplasm, representing less than 1% of all breast carcinomas. The present study repor...

  3. Histopathological and in vivo evidence of regucalcin as a protective molecule in mammary gland carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Ricardo; Vaz, Cátia V.; Maia, Cláudio J. [CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Gomes, Madalena [IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Porto (Portugal); Gama, Adelina [Department of Veterinary Sciences, Animal and Veterinary Science Research Center (CECAV), University of Trás-os-Montes and Alto Douro (UTAD) (Portugal); Alves, Gilberto; Santos, Cecília R. [CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal); Schmitt, Fernando [IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Porto (Portugal); Medical Faculty, University of Porto, Porto (Portugal); Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto (Canada); Department of Pathology, University Health Network, Toronto (Canada); Socorro, Sílvia, E-mail: ssocorro@fcsaude.ubi.pt [CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã (Portugal)

    2015-01-15

    Regucalcin (RGN) is a calcium-binding protein, which has been shown to be underexpressed in cancer cases. This study aimed to determine the association of RGN expression with clinicopathological parameters of human breast cancer. In addition, the role of RGN in malignancy of mammary gland using transgenic rats overexpressing the protein (Tg-RGN) was investigated. Wild-type (Wt) and Tg-RGN rats were treated with 7,12-dimethylbenz[α]anthracene (DMBA). Carcinogen-induced tumors were histologically classified and the Ki67 proliferation index was estimated. Immunohistochemistry analysis showed that RGN immunoreactivity was negatively correlated with the histological grade of breast infiltrating ductal carcinoma suggesting that progression of breast cancer is associated with loss of RGN. Tg-RGN rats displayed lower incidence of carcinogen-induced mammary gland tumors, as well as lower incidence of invasive forms. Moreover, higher proliferation was observed in non-invasive tumors of Wt animals comparatively with Tg-RGN. Overexpression of RGN was associated with diminished expression of cell-cycle inhibitors and increased expression of apoptosis inducers. Augmented activity of apoptosis effector caspase-3 was found in the mammary gland of Tg-RGN. RGN overexpression protected from carcinogen-induced mammary gland tumor development and was linked with reduced proliferation and increased apoptosis. These findings indicated the protective role of RGN in the carcinogenesis of mammary gland. - Highlights: • RGN immunoreactivity was negatively correlated with breast cancer differentiation. • Transgenic overexpression of RGN diminished incidence of carcinogen-induced tumors. • Transgenic overexpression of RGN restricted proliferation and fostered apoptosis. • RGN has a protective role in the carcinogenesis of mammary gland.

  4. Mammary Hypertrophy in an Ovariohysterectomized Cat

    OpenAIRE

    Pukay, B.P.; Stevenson, D.A.

    1983-01-01

    A four year old ovariohysterectomized domestic short-haired cat under treatment for behavioral urine spraying and idiopathic alopecia developed mammary gland hypertrophy following treatment with megestrol acetate. Withdrawal of the progestin and treatment with androgen failed to cause regression of the hypertrophy. The affected mammary gland was surgically excised and recovery was uneventful.

  5. escherichia coli serotypes confirmed in experimental mammary ...

    African Journals Online (AJOL)

    DJFLEX

    SEROTYPES CONFIRMED IN EXPERIMENTAL MAMMARY GLAND. INFECTIONS. P. A. AKPAN AND ... 037, 02a and 109) in mammary glands of experimental cows (cow 105, 107 and 102 respectively). Pathogenicity of the E. coli which ..... Akpan, P. A and Ikpeme, E. U., 2005. pathology of. Experimental Escherichia Coli ...

  6. ER and PR signaling nodes during mammary gland development.

    Science.gov (United States)

    Tanos, Tamara; Rojo, Lucia; Echeverria, Pablo; Brisken, Cathrin

    2012-07-19

    The ovarian hormones estrogen and progesterone orchestrate postnatal mammary gland development and are implicated in breast cancer. Most of our understanding of the molecular mechanisms of estrogen receptor (ER) and progesterone receptor (PR) signaling stems from in vitro studies with hormone receptor-positive cell lines. They have shown that ER and PR regulate gene transcription either by binding to DNA response elements directly or via other transcription factors and recruiting co-regulators. In addition they cross-talk with other signaling pathways through nongenomic mechanisms. Mouse genetics combined with tissue recombination techniques have provided insights about the action of these two hormones in vivo. It has emerged that hormones act on a subset of mammary epithelial cells and relegate biological functions to paracrine factors. With regards to hormonal signaling in breast carcinomas, global gene expression analyses have led to the identification of gene expression signatures that are characteristic of ERα-positive tumors that have stipulated functional studies of hitherto poorly understood transcription factors. Here, we highlight what has been learned about ER and PR signaling nodes in these different systems and attempt to lay out in which way the insights may converge.

  7. Progesterone receptor isoform analysis by quantitative real-time polymerase chain reaction in formalin-fixed, paraffin-embedded canine mammary dysplasias and tumors

    DEFF Research Database (Denmark)

    Guil-Luna, S.; Stenvang, Jan; Brünner, Nils

    2014-01-01

    Cloning and sequencing of the progesterone receptor gene in dogs have revealed 2 isoforms, A and B, transcribed from a single gene. Distribution of isoforms A and B in canine mammary lesions has hitherto been investigated only by Western blot analysis. This study analyzed progesterone receptor...... and its isoforms in formalin-fixed, paraffin-embedded tissue samples from canine mammary lesions (4 dysplasias, 10 benign tumors, and 46 carcinomas) using 1-step SYBR Green quantitative real-time polymerase chain reaction (RT-qPCR). Progesterone receptor was expressed in 75% of dysplasias, all benign...... of the canine mammary gland. These findings will facilitate future research into the role of progesterone receptor isoforms in the progression of canine mammary tumors....

  8. Refractive index of carcinogen-induced rat mammary tumours

    Science.gov (United States)

    Zysk, Adam M.; Chaney, Eric J.; Boppart, Stephen A.

    2006-05-01

    Near-infrared optical techniques for clinical breast cancer screening in humans are rapidly advancing. Based on the computational inversion of the photon diffusion process through the breast, these techniques rely on optical tissue models for accurate image reconstruction. Recent interest has surfaced regarding the effect of refractive index variations on these reconstructions. Although many data exist regarding the scattering and absorption properties of normal and diseased tissue, no measurements of refractive index appear in the literature. In this paper, we present near-infrared refractive index data acquired from N-methyl-N-nitrosourea-induced rat mammary tumours, which are similar in pathology and disease progression to human ductal carcinoma. Eight animals, including one control, were employed in this study, yielding data from 32 tumours as well as adjacent adipose and connective tissues.

  9. Imaging mammary diagnostics. Diagnostic techniques, archetypical findings, differential diagnostcs and interventions.. 2. rev. and enl. ed.; Bildgebende Mammadiagnostik. Untersuchungstechnik, Befundmuster, Differenzialdiagnose und Interventionen. Kartonierte Sonderausgabe

    Energy Technology Data Exchange (ETDEWEB)

    Heywang-Koebrunner, S. [Martin-Luther-Univ., Halle-Wittenberg (Germany). Klinik fuer Diagnostische Radiologie; Schreer, I. (eds.) [Mamma-Zentrum des UK Kiel (Germany). Klinik fuer Geburtshilfe und Gynaekologie

    2008-07-01

    The book includes the following chapters: I. Methodology: anamnesis and interview; clinical evidence, mammography, sonography, magnetic resonance tomography, new imaging techniques (scintigraphy, PET), transcutaneous biopsy, pre-operative marking; II. phenotypes: normal mammary glands, mastopathics, cysts, benign tumors, inflammatory diseases, in-situ carcinomas, invasive carcinomas, lymphomas, other semi-malign and malign tumors, post-traumatic, post-surgical and post-therapeutic changes, skin changes, male mamma, screening, continuative diagnostics of screening evidence and problem solving for symptomatic patients.

  10. Characterization of Spontaneous Mammary Tumors in Domestic Djungarian Hamsters (Phodopus sungorus).

    Science.gov (United States)

    Yoshimura, H; Kimura-Tsukada, N; Ono, Y; Michishita, M; Ohkusu-Tsukada, K; Matsuda, Y; Ishiwata, T; Takahashi, K

    2015-11-01

    Mammary tumors that spontaneously occurred in domestic Djungarian hamsters (Phodopus sungorus) were histologically examined. Forty-five mammary tumors included 14 adenomas, 18 adenocarcinomas, 1 lipid-rich carcinoma, 2 adenoacanthomas, 2 malignant adenomyoepitheliomas, 1 benign mixed tumor, and 7 "balloon cell" carcinosarcomas. The latter 4 types were newly recognized neoplasms in Djungarian hamsters. The relatively high incidence of spontaneous mammary carcinosarcomas in domestic Djungarian hamsters is intriguing. Carcinosarcomas exhibited anomalous histological features made up of a mixture of glandular cells, polygonal cells (including "balloon cells"), and sarcomatous spindle cells in varying proportions. Transitional features from glandular cells to polygonal cells and subsequently to sarcomatous spindle cells were observed. Using immunohistochemistry, we observed that glandular cells exhibited an epithelial phenotype (cytokeratin(+)/vimentin(-)), spindle cells exhibited a mesenchymal phenotype (cytokeratin(-)/vimentin(+)), and polygonal cells exhibited an intermediate phenotype (cytokeratin(+)/vimentin(+)). Reduction or loss of β-catenin expression and gain of S100A4 expression were observed in polygonal and spindle cells. The polygonal cell population included a varying number of characteristic cells that were expanded by large intracytoplasmic vacuoles. Electron microscopy revealed that these "balloon cells" had large cytoplasmic lumens lined by microvilli. These observations suggest that epithelial-mesenchymal transition may account for the pathogenesis of mammary carcinosarcomas in Djungarian hamsters. © The Author(s) 2015.

  11. Adenoid cystic carcinoma of the mandible : Case report | Lawal ...

    African Journals Online (AJOL)

    Adenoid Cystic Carcinoma (ACC) is an uncommon salivary gland malignancy which can also develop in the mucus glands of the larynx, trachea, bronchus, lungs and mammary glands besides the head and neck region (1). The most frequently affected sites are the parotid gland, sub-mandibular gland and palate, whereas ...

  12. Benign lymph node inclusions mimicking metastatic carcinoma.

    OpenAIRE

    Fisher, C. J.; Hill, S.; Millis, R. R.

    1994-01-01

    AIMS--To draw attention to non-neoplastic inclusions in axillary lymph nodes removed from women with primary breast cancer which may be mistaken for metastases. METHODS--Five examples of non-malignant inclusions were detected in axillary lymph nodes removed from women with mammary carcinoma. Immunohistochemical staining for CAM 5.2 and S100 markers, as well as morphological assessment were performed. RESULTS--Three of the five cases comprised naevus cells and two heterotopic epithelial elemen...

  13. STAT6 Deletion Enhances Immunity to Mammary Carcinoma

    Science.gov (United States)

    2005-06-01

    diabetes in D.G. Quiiceno, J. B. choa, and A. C. Ochoa. 2003. L-Arginine consumption by neonatal mice. J. hinininol. 157:978. 17. Ho, W. Y., M. P. Cooke...bottomed plates with 5 X 10’ DOI 1.10 T cells, the is 1 o indicated number of DCs, and 10 ).g ovalbumin (Sigma) orl p.g ova peptide 0 is o 323-339...CD4+CD25’ immnoregulatory T cells that control autoimmune diabetes . In- munit., 12:431. immunity to 4T1 (Clements and Ostrand-Rosenberg, unpublished

  14. Histopathologic and dietary prognostic factors for canine mammary carcinoma.

    Science.gov (United States)

    Shofer, F S; Sonnenschein, E G; Goldschmidt, M H; Laster, L L; Glickman, L T

    1989-01-01

    Histologic and dietary prognostic factors for survival following naturally occurring breast cancer were studied for 145 pet dogs. Information was collected from the dog's owner and veterinarian regarding medical and reproductive history, nutritional status, treatment, tumor recurrence, and length of survival. The usual intake of all dog and table foods consumed 1 year prior to diagnosis was obtained using a validated quantitative food frequency questionnaire. A histologic malignancy score was derived based on 7 histopathologic criteria. The mean age of the dogs was 10.4 +/- 2.5 years; 37% had been ovariohysterectomized prior to diagnosis. Product-limit estimates of survival indicated that 6 factors, namely body conformation 1 year prior to diagnosis (p = 0.03), histologic tumor type (p = 0.004), histologic malignancy score (p = 0.02), histologic invasion (p = 0.002), tumor recurrence (p less than 0.0001), and completeness of surgery (p = 0.01) were of prognostic significance. In addition, when dogs were characterized by the percent of total calories they derived from fat and protein, the median survival time for dogs in the low fat group (less than 39%) with protein greater than 27%, 23-27%, and less than 23% was 3 years, 1.2 years, and 6 months, respectively (p = 0.008). For dogs in the high fat group (greater than or equal to 39%), there was no difference in survival for the different intake levels of dietary protein (p = 0.84). When these data were fitted to a proportional hazards model, recurrence, histologic score, tumor type, percent of calories derived from protein, fat group, and a protein-fat group interaction term were statistically significant. Predicted 1 year survival for dogs on a low fat diet with 15%, 25%, and 35% of total calories derived from protein was 17%, 69%, and 93%, respectively.

  15. Immunological Prevention of Spontaneous Mammary Carcinoma in Transgenic Mice

    Science.gov (United States)

    2001-08-01

    multifocal tumors in breast, salivary, harderian and epididymal tissues developed in MMTV-NeuBrooks PC, Clark RAF , and Cheresh DA (1994a). Require...Shiloni E, Karp SE, Custer MC et al. Retroviral transduction of interferon-gamma cDNA into a nonimmunogenic marine fibro- sarcoma: Generation of T

  16. Immunological Prevention of Spontaneous Mammary Carcinoma in Transgenic Mice

    Science.gov (United States)

    1999-08-01

    collaboration with Dr. Luc Van Kaer , Nashville, TN (15)] TASK 2-3. PROPHYLACTIC VACCINATION WITH CYTOKINE GENE-TRANSDUCED TUMOR CELLS. The aim is to: a) induce...S, Boesteanu A, Joyce S, Van Kaer L, CDldl mutant mice are deficient in natural T cells that promptly produce IL-4. Immunity 6:469-677,1998 16

  17. Unusual ultrasonography findings of recurred mammary fibermatosis mimicking subareolar mastitis: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Hwa Sung; Kim, Young Seon; Bae, Young Kyung [College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

    2016-09-15

    Fibromatosis, also known as an extra-abdominal desmoid tumor, rarely occurs in the breast and is often mistaken for carcinoma, clinically and radiologically. Desmoid tumor is a monoclonal myofibroblastic neoplasm which is locally aggressive, but rarely metastasizes. We herein report a case of a 64-year-old woman who experienced two episodes of recurrence of mammary fibromatosis. The mass was initially detected by screening mammography. It appeared as an irregularly shaped mass which was confined within the mammary zone. Recurrences were excised from the right breast 10 and 17 months later. The second recurrence occurred in the subareolar area accompanied by skin thickening and showed an anechoic component on ultrasonography, which mimicked subareolar mastitis with an abscess.

  18. Selenium in human mammary carcinogenesis

    DEFF Research Database (Denmark)

    Overvad, Kim; Grøn, P.; Langhoff, Otto

    1991-01-01

    In a case-referent study on the possible role of selenium in human mammary carcinogenesis, serum selenium was found to be 79 +/- 12 micrograms/l in 66 cases and 81 +/- 12 micrograms/l in 93 referents. An internal trend in serum selenium was observed among cases (TNM stage I 81 +/- 11 micrograms....../l and TNM stage II 76 +/- 13 micrograms selenium/l), indicating disease-mediated changes. The evaluation of selenium as a risk indicator in human breast cancer was therefore restricted to TNM stage I patients (n = 36). Multiple logistic regression analyses including variables associated with selenium levels...... revealed no association between selenium levels and breast cancer risk....

  19. Polarized dermoscopy of mammary Paget disease*

    Science.gov (United States)

    de Crignis, Giselly Silva Neto; de Abreu, Luciana; Buçard, Alice Mota; Barcaui, Carlos Baptista

    2013-01-01

    Mammary Paget's disease is a rare intraepithelial adenocarcinoma, located on the nipple/areola complex, highly associated with breast cancer. Although the international literature emphasizes the dermatoscopic pattern of mammary Paget's disease pigmented variant, the authors describe the dermoscopic findings of classical Paget's disease and demonstrate the presence of chrysalis-like structures, criteria recently described in the literature and not yet reported in Paget's disease. PMID:23739693

  20. Mammary Cancer and Activation of Transposable Elements

    Science.gov (United States)

    2015-03-01

    retrotransposon expression is a later event, and unlikely to play a direct role in cancer ontogeny. 15. SUBJECT TERMS Breast cancer , epigenetic, DNA...transcriptionally activated during pregnancy and lactation, and the mice are predisposed to develop mammary cancer after a minimum of 3 pregnancies and... pregnancy and lactation. After 3 pregnancies and lactations, but not after 1 pregnancy and lactation, females develop mammary cancers at an average

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2016-10-01

    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.

  3. Longitudinal Claudin Gene Expression Analyses in Canine Mammary Tissues and Thereof Derived Primary Cultures and Cell Lines

    Directory of Open Access Journals (Sweden)

    Susanne C. Hammer

    2016-09-01

    Full Text Available Human and canine mammary tumours show partial claudin expression deregulations. Further, claudins have been used for directed therapeutic approaches. However, the development of claudin targeting approaches requires stable claudin expressing cell lines. This study reports the establishment and characterisation of canine mammary tissue derived cell lines, analysing longitudinally the claudin-1, -3, -4 and -7 expressions in original tissue samples, primary cultures and developed cell lines. Primary cultures were derived from 17 canine mammary tissues: healthy, lobular hyperplasia, simple adenoma, complex adenoma, simple tubular carcinoma, complex carcinoma, carcinoma arising in a benign mixed tumour and benign mixed tissue. Cultivation was performed, if possible, until passage 30. Claudin mRNA and protein expressions were analysed by PCR, QuantiGene Plex Assay, immunocytochemistry and immunofluorescence. Further, cytokeratin expression was analysed immunocytochemically. Cultivation resulted in 11 established cell lines, eight showing epithelial character. In five of the early passages the claudin expressions decreased compared to the original tissues. In general, claudin expressions were diminished during cultivation. Three cell lines kept longitudinally claudin, as well as epithelial marker expressions, representing valuable tools for the development of claudin targeted anti-tumour therapies.

  4. Mammary blood flow and cardiac output during initiated involution of the mammary gland in the rabbit.

    Science.gov (United States)

    Jones, C S; Parker, D S

    1988-01-01

    1. Cardiac output and its distribution to the mammary gland, kidneys, heart, liver and gastrointestinal tract were measured in conscious rabbits at day 1, day 3 and day 6 after removal of the young at day 0. 2. There was no change in cardiac output, proportion of cardiac output delivered to the mammary gland or mammary blood flow 24 hr after the last suckling period. After a further 48 hr there was a significant reduction in the cardiac output, proportion of the cardiac output and blood flow to the mammary gland compared to the values measured in lactating animals. 3. There was no significant difference in blood flow to the other organs although there were changes in the proportion of the cardiac output delivered to the heart, kidney and liver during this period. 4. The change in uptake of glucose, acetate, non-esterified fatty acids and triacylglycerols by the mammary gland are discussed in relation to the reabsorption of milk components.

  5. Secretory carcinoma in a 79-year-old woman: an exceptionally rare type of breast carcinoma

    Directory of Open Access Journals (Sweden)

    Nelson Montalvo

    2016-12-01

    Full Text Available Secretory breast carcinoma is an exceptionally rare mammary gland neoplasia described mainly in adult females and children of both sexes, and very rarely in the elderly. It has particular histopathological and immunohistochemical features and a favorable prognosis. We report the case of a 79-year-old Hispanic woman with a palpable breast mass. Currently, the patient is disease free after a follow- up period of 6 years without local recurrence or axillary lymph-nodes nor distant metastases.

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

    Science.gov (United States)

    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

  7. Human breast cancer cells are redirected to mammary epithelial cells upon interaction with the regenerating mammary gland microenvironment in-vivo.

    Directory of Open Access Journals (Sweden)

    Karen M Bussard

    Full Text Available Breast cancer is the second leading cause of cancer deaths in the United States. At present, the etiology of breast cancer is unknown; however the possibility of a distinct cell of origin, i.e. a cancer stem cell, is a heavily investigated area of research. Influencing signals from the tissue niche are known to affect stem cells. Literature has shown that cancer cells lose their tumorigenic potential and display 'normal' behavior when placed into 'normal' ontogenic environments. Therefore, it may be the case that the tissue microenvironment is able to generate signals to redirect cancer cell fate. Previously, we showed that pluripotent human embryonal carcinoma cells could be redirected by the regenerating mammary gland microenvironment to contribute epithelial progeny for 'normal' gland development in-vivo. Here, we show that that human metastatic, non-metastatic, and metastasis-suppressed breast cancer cells proliferate and contribute to normal mammary gland development in-vivo without tumor formation. Immunochemistry for human-specific mitochondria, keratin 8 and 14, as well as human-specific milk proteins (alpha-lactalbumin, impregnated transplant hosts confirmed the presence of human cell progeny. Features consistent with normal mammary gland development as seen in intact hosts (duct, lumen formation, development of secretory acini were recapitulated in both primary and secondary outgrowths from chimeric implants. These results suggest the dominance of the tissue microenvironment over cancer cell fate. This work demonstrates that cultured human breast cancer cells (metastatic and non-metastatic respond developmentally to signals generated by the mouse mammary gland microenvironment during gland regeneration in-vivo.

  8. Significant overlap between human genome-wide association-study nominated breast cancer risk alleles and rat mammary cancer susceptibility loci.

    Science.gov (United States)

    Sanders, Jennifer; Samuelson, David J

    2014-01-27

    Human population-based genome-wide association (GWA) studies identify low penetrance breast cancer risk alleles; however, GWA studies alone do not definitively determine causative genes or mechanisms. Stringent genome- wide statistical significance level requirements, set to avoid false-positive associations, yield many false-negative associations. Laboratory rats (Rattus norvegicus) are useful to study many aspects of breast cancer, including genetic susceptibility. Several rat mammary cancer associated loci have been identified using genetic linkage and congenic strain based-approaches. Here, we sought to determine the amount of overlap between GWA study nominated human breast and rat mammary cancer susceptibility loci. We queried published GWA studies to identify two groups of SNPs, one that reached genome-wide significance and one comprised of SNPs failing a validation step and not reaching genome- wide significance. Human genome locations of these SNPs were compared to known rat mammary carcinoma susceptibility loci to determine if risk alleles existed in both species. Rat genome regions not known to associate with mammary cancer risk were randomly selected as control regions. Significantly more human breast cancer risk GWA study nominated SNPs mapped at orthologs of rat mammary cancer loci than to regions not known to contain rat mammary cancer loci. The rat genome was useful to predict associations that had met human genome-wide significance criteria and weaker associations that had not. Integration of human and rat comparative genomics may be useful to parse out false-negative associations in GWA studies of breast cancer risk.

  9. Total encephalic radiotherapy and concomitant administering of trastuzumab for brain metastases of a mammary carcinoma with HER2 overexpression: experience of the Curie Institute; Radiotherapie encephalique totale et administration concomitante de trastuzumab pour des metastases cerebrales d'un carcinome mammaire surexprimant HER2: experience de l'institut Curie

    Energy Technology Data Exchange (ETDEWEB)

    Chargari, C.; Idrissi, H.R.; Pierga, J.Y.; Bollet, M.; Dieras, V.; Campana, F.; Cottu, P.; Fourquet, A.; Kirova, Y. [Institut Curie, 75 - Paris (France)

    2010-10-15

    The authors report a retrospective study of assessment of the tolerance to and of the activity of the trastuzumab in association with a total encephalic irradiation. The study is based on 31 patients suffering from brain metastases in relationship with a mammary cancer with HER2 expression, and who have been submitted to a total encephalic radiotherapy with a trastuzumab treatment. This medicine appears to be efficient and harmless. A clinic trial should confirm these results. Short communication

  10. Functional screen of paracrine signals in breast carcinoma fibroblasts.

    Directory of Open Access Journals (Sweden)

    Gui Su

    Full Text Available Stromal fibroblasts actively participate in normal mammary gland homeostasis and in breast carcinoma growth and progression by secreting paracrine factors; however, little is known about the identity of paracrine mediators in individual patients. The purpose of this study was to characterize paracrine signaling pathways between breast carcinoma cells and breast carcinoma-associated fibroblasts (CAF or normal mammary fibroblasts (NF, respectively. CAF and NF were isolated from breast carcinoma tissue samples and adjacent normal mammary gland tissue of 28 patients. The fibroblasts were grown in 3D collagen gel co-culture with T47D human breast carcinoma cells and T47D cell growth was measured. CAF stimulated T47D cell growth to a significantly greater degree than NF. We detected a considerable inter-individual heterogeneity of paracrine interactions but identified FGF2, HB-EGF, heparanase-1 and SDF1 as factors that were consistently responsible for the activity of carcinoma-associated fibroblasts. CAF from low-grade but not high-grade carcinomas required insulin-like growth factor 1 and transforming growth factor beta 1 to stimulate carcinoma growth. Paradoxically, blocking of membrane-type 1 matrix metalloprotease stimulated T47D cell growth in co-culture with NF. The results were largely mirrored by treating the fibroblasts with siRNA oligonucleotides prior to co-culture, implicating the fibroblasts as principal production site for the secreted mediators. In summary, we identify a paracrine signaling network with inter-individual commonalities and differences. These findings have significant implications for the design of stroma-targeted therapies.

  11. Positional Variations in Mammary Gland Development and Cancer

    OpenAIRE

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

    2013-01-01

    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...

  12. Mammary gland stem cells: More puzzles than explanations

    Indian Academy of Sciences (India)

    Mammary gland stem cells (MaSC) have not been identified in spite of extensive research spanning over several decades. This has been primarily due to the complexity of mammary gland structure and its development, cell heterogeneity in the mammary gland and the insufficient knowledge about MaSC markers.

  13. Gynecomastia and mammary gland adenocarcinoma in a Nubian buck.

    Science.gov (United States)

    Wooldridge, A A; Gill, M S; Lemarchand, T; Eilts, B; Taylor, H W; Otterson, T

    1999-09-01

    A 6-year-old Nubian buck was presented for bilateral mammary gland enlargement. Gynecomastia and mastitis were diagnosed, and bilateral mastectomy was performed. Histological examination showed mammary adenocarcinoma, active lactation, hyperplasia, and abscessation. Karyotyping showed a normal male. Clinical, therapeutic, etiologic, and epidemiologic aspects of gynecomastia and mammary gland adenocarcinoma are discussed.

  14. Gynecomastia and mammary gland adenocarcinoma in a Nubian buck.

    OpenAIRE

    Wooldridge, A A; Gill, M S; Lemarchand, T; Eilts, B; Taylor, H. W.; Otterson, T

    1999-01-01

    A 6-year-old Nubian buck was presented for bilateral mammary gland enlargement. Gynecomastia and mastitis were diagnosed, and bilateral mastectomy was performed. Histological examination showed mammary adenocarcinoma, active lactation, hyperplasia, and abscessation. Karyotyping showed a normal male. Clinical, therapeutic, etiologic, and epidemiologic aspects of gynecomastia and mammary gland adenocarcinoma are discussed.

  15. Mammary fibroadenomatoid hyperplasia in a heifer

    Directory of Open Access Journals (Sweden)

    Lorena Ferreira Silva

    Full Text Available ABSTRACT: This manuscript described the anatomopathological and immunohistochemical findings in a rare case of mammary fibroadenomatoid hyperplasia in a 12-month-old Holstein heifer. A yellow, multilobulated, firm 20cm x 9cm x 6.5cm mass affecting the right quarters of the udder was observed. Total mastectomy was performed. Microscopic evaluation revealed severe hyperplasia of the mammary epithelium and numerous well-differentiated and mildly pleomorphic acini. Additionally, moderate proliferation of the fibrous connective tissue and the myoepithelial cells near the proliferating acini was evident. About 50% of the proliferating epithelial cells showed positive nuclear labeling for estrogen and progesterone receptors, and approximately one-third were positive for Ki-67. In addition, the myoepithelial cells exhibited diffuse nuclear immunoreactivity for p63. Based on the clinical, morphologic, and immunohistochemical findings, a diagnosis of mammary fibroadenomatoid hyperplasia with probable influence of ovarian steroids was made.

  16. Of Microenvironments and Mammary Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Effects of physical activity and restricted energy intake on chemically induced mammary carcinogenesis.

    Science.gov (United States)

    Jiang, Weiqin; Zhu, Zongjian; Thompson, Henry J

    2009-04-01

    In the field of energetics and cancer, little attention has been given to whether energy balance directed interventions designed to regulate body weight by increasing energy expenditure versus reducing energy intake have an equivalent effect on the development of breast cancer. The objective of this experiment was to determine the effects on mammary carcinogenesis of physical activity (PA), achieved via running on an activity wheel, or restricted energy intake (RE). Food intake of PA and RE rats was controlled so that both groups had the same net energy balance determined by growth rate, which was 92% of the sedentary control group (SC). A total of 135 female Sprague-Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter were randomized to either SC, PA, or RE. Mammary cancer incidence was 97.8%, 88.9%, and 84.4% and cancer multiplicity was 3.66, 3.11, and 2.64 cancers/rat in SC, RE, and PA, respectively (SC versus PA, P = 0.02 for incidence and P = 0.03 for multiplicity). Analyses of mammary carcinomas revealed that cell proliferation-associated proteins were reduced and caspase-3 activity and proapoptotic proteins were elevated by PA or RE relative to SC (P < 0.05). It was observed that these effects may be mediated, in part, by activation of AMP-activated protein kinase and down-regulation of protein kinase B and the mammalian target of rapamycin.

  18. Lentivirus-Mediated Oncogene Introduction into Mammary Cells In Vivo Induces Tumors

    Directory of Open Access Journals (Sweden)

    Stefan K. Siwko

    2008-07-01

    Full Text Available We recently reported the introduction of oncogene-expressing avian retroviruses into somatic mammary cells in mice susceptible to infection by transgenic expression of tva, encoding the receptor for subgroup A avian leukosis-sarcoma virus (ALSV. Because ALSV-based vectors poorly infect nondividing cells, they are inadequate for studying carcinogenesis initiated from nonproliferative cells (e.g., stem cells. Lentivirus pseudotyped with the envelope protein of ALSV infects nondividing TVA-producing cells in culture but has not previously been tested for introducing genes in vivo. Here, we demonstrate that these vectors infected mammary cells in vivo when injected into the mammary ductal lumen of mice expressing tva under the control of the keratin 19 promoter. Furthermore, intraductal injection of this lentiviral vector carrying the polyoma middle T antigen gene induced atypical ductal hyperplasia and ductal carcinoma in situ-like premalignant lesions in 30 days and palpable invasive tumors at a median latency of 3.3 months. Induced tumors were a mixed epithelial/myoepithelial histologic diagnosis, occasionally displayed squamous metaplasia, and were estrogen receptor-negative. This work demonstrates the first use of a lentiviral vector to introduce oncogenes for modeling cancer in mice, and this vector system may be especially suitable for introducing genetic alterations into quiescent cells in vivo.

  19. Mammary tumorigenesis by radiation and its prevention

    Energy Technology Data Exchange (ETDEWEB)

    Onoda, Makoto; Suzuki, Keiko; Inano, Hiroshi [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-06-01

    Since the breast cancer in women emerged as an important risk associated with exposure to ionizing radiation, we have investigated to clarify the relationship between the induction of mammary tumors by irradiation and the developmental stage of the mammary glands that regulated by the action of endocrine hormones. Besides the radiation, epidemiological studies showed that the process of biosynthesis/metabolism of steroid hormones and hyperlipidemia may be associated with an increased risk of mammary carcinogenesis. In this context, we have undertaken investigations to evaluate the anti-carcinogenic activities of dehydroepiandrosterone (DHEA), a major secretory steroid of the adrenal glands, bezafibrate (BEZF), an anti-hyperlipidemic drug derived from clofibrate, and simvastatin (SIMV), a prodrug of a specific inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, against diethylstilbestrol (DES)-dependent promotion/progression of rat mammary tumors initiated by {gamma}-rays. Pregnant Wistar-MS rats received whole-body irradiation with 2.6 Gy of {gamma}-rays from a {sup 60}Co source at day-20 of pregnancy. The mother rats were fed a diet containing either 0.6% DHEA, 0.15% BEZF or 0.03% SIMV beginning immediately after weaning. They were then implanted subcutaneously with a pellet of DES (3 mg/pellet) in the interscapular area 30 days after termination of nursing and were observed for 1 year for detection of palpable mammary tumors starting from the time of pellet implantation. The administration of dietary DHEA, BEZF or SIMV together with DES implantation in rats irradiated in late pregnancy significantly decreased the total incidence of mammary tumors to 35%, 27% and 36%, respectively, for the 1 year period, while higher tumor incidence (96%, 90% and 88%) was observed in rats fed controldiet. However, neither the number of mammary tumors per tumor-bearing rat nor the latency period in the drug treated groups was different from that observed in the control group

  20. Thymic carcinoma

    Directory of Open Access Journals (Sweden)

    Vitória Homem Machado

    2016-10-01

    Full Text Available Thymic carcinomas are a heterogeneous group of aggressive, invasive epithelial malignancies. Their incidence is rare, occurring predominantly in middle-aged men. Here we present the typical imaging findings of a thymic carcinoma. The combination of imaging characteristics with tumor location and patient age provides a roadmap for approaching the differential diagnosis. Keywords: Thymus Gland; carcinoma; mediastinal neoplasms

  1. Stromal Effects on Mammary Gland Development and Breast Cancer

    Science.gov (United States)

    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.

  2. STAT5A Regulates the Survival of Mammary Epithelial Cells and the Development of Mammary Cancer

    National Research Council Canada - National Science Library

    Humphreys, Robin

    2000-01-01

    The in vivo relationship between epidermal growth factor (EGF) and prolactin/Jak/Stat signaling pathways in mammary gland development and tumorigenesis was explored in transgenic nice overexpressing the TGF alpha gene (TGFalphaTG...

  3. Carcinoma espinocelular da mama: relato de um caso Squamous cell carcinoma of the breast tissue: a case report

    Directory of Open Access Journals (Sweden)

    Rubens José Pereira

    1999-08-01

    Full Text Available O carcinoma espinocelular do parênquima mamário é um tipo raro de neoplasia, representando menos de 1% de todos os carcinomas mamários. Esse trabalho relata a condução de um caso diagnosticado e tratado no Serviço de Ginecologia e Mama do Hospital Araújo Jorge/ACCG. São discutidos a apresentação clínica, o diagnóstico e o prognóstico destes tumores.Squamous cell carcinoma of the mammary tissue is a very rare neoplasm, representing less than 1% of all breast carcinomas. The present study reports a case of squamous cell carcinoma of the breast, treated at the Hospital Araújo Jorge/ACCG. The tumor diagnosis, treatment and prognosis are also discussed.

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

    OpenAIRE

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

    2002-01-01

    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 i...

  5. Parotid carcinoma

    DEFF Research Database (Denmark)

    Sørensen, Kristine Bjørndal; Godballe, Christian; de Stricker, Karin

    2006-01-01

    OBJECTIVES: Our aim is to investigate the expression of kit protein (KIT) and epidermal growth factor receptor (EGFR) in parotid carcinomas in order to correlate the expression to histology and prognosis. Further we want to perform mutation analysis of KIT-positive adenoid cystic carcinomas....... PATIENTS AND METHODS: Formalin-fixed paraffin-embedded sections from 73 patients with parotid gland carcinomas were used for the study. The sections were stained with both KIT and EGFR polyclonal antibodies. Twelve KIT-positive adenoid cystic carcinomas were examined for c-kit mutation in codon 816....... RESULTS: Of all carcinomas 25% were KIT-positive and 79% were EGFR-positive. Ninety-two percentage of the adenoid cystic carcinomas were KIT-positive. None of the adenoid cystic carcinomas had mutations in codon 816 of the c-kit gene. CONCLUSION: Neither KIT- nor EGFR-expression seem to harbour...

  6. FRACTAL DIMENSIONALITY ANALYSIS OF MAMMARY GLAND THERMOGRAMS

    OpenAIRE

    Yu. E. Lyah; V. G. Guryanov; E. A. Yakobson

    2016-01-01

    Thermography may enable early detection of a cancer tumour within a mammary gland at an early, treatable stage of the illness, but thermogram analysis methods must be developed to achieve this goal. This study analyses the feasibility of applying the Hurst exponent readings algorithm for evaluation of the high dimensionality fractals to reveal any possible difference between normal thermograms (NT) and malignant thermograms (MT).

  7. Tuberculosis and metastatic carcinoma coexistence in axillary lymph node: A case report

    Directory of Open Access Journals (Sweden)

    K Chandramohan

    2003-04-01

    Full Text Available Abstract Background Coexistence of cancer and tuberculosis in axillary lymph nodes is rare. Only seven cases have been reported in the literature. Case Report We report here a case of infiltrating ductal carcinoma breast metastasizing to the axillary lymph node along with tubercular granuloma in the same lymph node without primary mammary or pulmonary tuberculosis. Conclusion Primary tuberculosis coexisting with carcinoma is of rare occurrence. A possibility should always be borne in mind especially in patients from endemic areas.

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

    Science.gov (United States)

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

    2002-01-01

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

  9. Culture models of human mammary epithelial cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Stampfer, Martha R.; Yaswen, Paul

    2000-11-10

    Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the know in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TFGB. We propose th at overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.

  10. Description of the prevalence, histologic characteristics, concomitant abnormalities, and outcomes of mammary gland tumors in companion rats (Rattus norvegicus): 100 cases (1990-2015).

    Science.gov (United States)

    Vergneau-Grosset, Claire; Keel, M Kevin; Goldsmith, Dayna; Kass, Philip H; Paul-Murphy, Joanne; Hawkins, Michelle G

    2016-11-15

    OBJECTIVE To describe the prevalence, histologic characteristics, concomitant abnormalities, and outcomes for various types of mammary gland tumors in companion rats (Rattus norvegicus). DESIGN Retrospective case series. ANIMALS 100 client-owned rats. PROCEDURES Medical records of companion rats that had an SC mass and were examined at a veterinary teaching hospital between 1990 and 2015 were reviewed. Information regarding the signalment, age at mass detection, reproductive sterilization status, histologic diagnosis of the SC mass, location of the initial and all subsequent SC masses, treatments administered, and clinical outcomes was extracted from each record and summarized. RESULTS 105 SC masses were initially detected in 100 rats. The most prevalent SC mass identified was mammary gland fibroadenoma (56/105 [53%]), followed by mammary gland carcinoma (13/105 [12%]). Overall, 26 of 105 (25%) masses were malignant. Sexually intact males were more likely to have nonmammary SC tumors than sexually intact females. In rats receiving no adjunctive treatment after excision of a mammary gland fibroadenoma (n = 16), a second fibroadenoma was detected 1 to 8 months after initial excision, at a median of 4.5 months after surgery. A concomitant pituitary gland tumor was identified in most rats with mammary gland fibroadenoma (21/28 [75%]) and other types of mammary gland tumors (10/17 [59%]). Fourteen of 35 (40%) rats with mammary gland fibroadenoma had concomitant reproductive tract abnormalities. CONCLUSION AND CLINICAL RELEVANCE Results suggested that, like other species, companion rats with SC masses should undergo a thorough diagnostic workup that includes histologic examination of the excised mass.

  11. Unusual apocrine carcinoma with neuroendocrine differentiation: a cutaneous neoplasm may be analogous to neuroendocrine carcinoma with apocrine differentiation of breast.

    Science.gov (United States)

    Li, Yang; Chen, Li-li; Li, Bin; Tian, Xiao-ying; Li, Zhi

    2015-06-10

    Cutaneous apocrine carcinoma (AC) is a rare adnexal neoplasm that histologically can mimic breast carcinoma metastatic to the skin or apocrine carcinoma arising in ectopic breast tissue. As extremely rare condition, neuroendocrine differentiation may be observed in AC although its etiology and pathogenesis is still unclear. We report here a case of unusual AC with neuroendocrine differentiation in right labium majus pudenda. A 43-year-old woman presented with a 6-month history of an asymptomatic pea-sized brownish nodule in right labium majus pudenda without enlargement of inguinal lymph nodes and bilateral breast nodules. The mass was totally resected. Microscopically, the tumor was solitary and located in the deep dermis without epidermal connection. Tumor cells were arranged in a micronodular or formed massive solid nests separated by densely fibroblastic stroma. Scattered glandular or rosette-like structures were identified within the tumor nodules. Immunohistochemically, the tumor cells were diffusely positive to CK7, CEA, GCDFP-15, synaptophysin, estrogen and progesterone receptors. Part of tumor cells expressed androgen receptor, but they were negative to CK20, CK5/6, p63 and S-100. Because of its rarity and histogenesis complexity, there exist diagnostic challenges for pathologists to differentiate cutaneous AC with neuroendocrine differentiation from other carcinomas with apocrine or neuroendocrine features. Our case demonstrates that the tumor shares some features with mammary carcinoma and might originate from mammary-like sweat gland in anogenital region. The results suggest that, for the first time, primary cutaneous AC with neuroendocrine differentiation may be analogous to the mammary neuroendocrine carcinoma with apocrine differentiation in histological feature and biological behavior. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7732276716685708.

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

    Science.gov (United States)

    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.

  13. Targeting the Prometastatic Microenvironment of the Involuting mammary gland

    Science.gov (United States)

    2016-09-01

    AWARD NUMBER: W81XWH-13-1-0290 TITLE: Targeting the Prometastatic Microenvironment of the Involuting Mammary Gland PRINCIPAL INVESTIGATOR...2016 4. TITLE AND SUBTITLE Targeting the Prometastatic Microenvironment of the Involuting mammary gland 5a. CONTRACT NUMBER Mammary Gland 5b. GRANT...complete) Task 3) Determine the pathological significance of gain and loss of LTBP1 in genetically engineered mouse models. (75% complete) Ø

  14. Human saliva as route of inter-human infection for mouse mammary tumor virus.

    Science.gov (United States)

    Mazzanti, Chiara Maria; Lessi, Francesca; Armogida, Ivana; Zavaglia, Katia; Franceschi, Sara; Al Hamad, Mohammad; Roncella, Manuela; Ghilli, Matteo; Boldrini, Antonio; Aretini, Paolo; Fanelli, Giovanni; Marchetti, Ivo; Scatena, Cristian; Hochman, Jacob; Naccarato, Antonio Giuseppe; Bevilacqua, Generoso

    2015-07-30

    Etiology of human breast cancer is unknown, whereas the Mouse Mammary Tumor Virus (MMTV) is recognized as the etiologic agent of mouse mammary carcinoma. Moreover, this experimental model contributed substantially to our understanding of many biological aspects of the human disease. Several data strongly suggest a causative role of MMTV in humans, such as the presence of viral sequences in a high percentage of infiltrating breast carcinoma and in its preinvasive lesions, the production of viral particles in primary cultures of breast cancer, the ability of the virus to infect cells in culture. This paper demonstrates that MMTV is present in human saliva and salivary glands. MMTV presence was investigated by fluorescent PCR, RT-PCR, FISH, immunohistochemistry, and whole transcriptome analysis. Saliva was obtained from newborns, children, adults, and breast cancer patients. The saliva of newborns is MMTV-free, whereas MMTV is present in saliva of children (26.66%), healthy adults (10.60%), and breast cancer patients (57.14% as DNA and 33.9% as RNA). MMTV is also present in 8.10% of salivary glands. RNA-seq analysis performed on saliva of a breast cancer patient demonstrates a high expression of MMTV RNA in comparison to negative controls. The possibility of a contamination by murine DNA was excluded by murine mtDNA and IAP LTR PCR. These findings confirm the presence of MMTV in humans, strongly suggest saliva as route in inter-human infection, and support the hypothesis of a viral origin for human breast carcinoma.

  15. Expression of Autoactivated Stromelysin-1 in Mammary Glands of Transgenic Mice Leads to a Reactive Stroma During Early Development

    Energy Technology Data Exchange (ETDEWEB)

    Thomasset, N.; Lochter, A.; Sympson, C.J.; Lund, L.R.; Williams, D.R.; Behrendtsen, O.; Werb, Z.; Bissell, M.J.

    1998-04-24

    cells produce fibronectin, collagens, proteoglycans, and some components of the BM, as well as a number of proteinases that can effectively degrade BM constituents. Stromal and epithelial cells of the mammary gland interact to regulate BM synthesis and degradation and, thus, mammary function. Matrix metalloproteinases (MMPs) are extracellular matrix (ECM)-degrading enzymes involved in mammary gland morphogenesis and involution. During late pregnancy and lactation, when the gland becomes fully functional, the expression of MMPs is low however, during involution, when the gland loses function and is remodeled, synthesis of ECM-degrading proteinases increases dramatically.11 Disturbance of the balance between MMPs and MMP inhibitors leads to either unscheduled involution or prolonged lactation. Mammary glands of virgin mice expressing an autoactivating stromelysin-1 (SL-1) transgene display supernumerary branches and precocious alveolar development, accompanied by the synthesis of {beta}-casein at levels found normally only during early pregnancy. During late pregnancy, increased expression of the SL-1 transgene leads to a reduction in expression of pregnancy-specific genes. Later in life, some SL-1 transgenic mice develop hyperplastic, dysplastic, and ductal carcinoma in situ-like lesions, as well as malignant tumors. Little is known about the sequence of changes that occurs before formation of an overt reactive stroma in breast cancer. In the present study, we address the question of whether and how the stromal compartment is altered as a consequence of inappropriate SL-1 transgene expression in the epithelium.

  16. The glucose transporter GLUT1 is required for ErbB2-induced mammary tumorigenesis.

    Science.gov (United States)

    Wellberg, Elizabeth A; Johnson, Stevi; Finlay-Schultz, Jessica; Lewis, Andrew S; Terrell, Kristina L; Sartorius, Carol A; Abel, E Dale; Muller, William J; Anderson, Steven M

    2016-12-20

    Altered tumor cell metabolism is an emerging hallmark of cancer; however, the precise role for glucose in tumor initiation is not known. GLUT1 (SLC2A1) is expressed in breast cancer cells and is likely responsible for avid glucose uptake observed in established tumors. We have shown that GLUT1 was necessary for xenograft tumor formation from primary mammary cells transformed with the polyomavirus middle-T antigen but that it was not necessary for growth after tumors had formed in vivo, suggesting a differential requirement for glucose depending on the stage of tumorigenesis. To determine whether GLUT1 is required early during mammary tumorigenesis, we crossed MMTV-NIC mice, which express activated HER2/NEU/ERBB2 and Cre recombinase, to Slc2a1 (Flox/Flox) (GLUT1(Flox/Flox)) mice to generate NIC-GLUT1(+/+), NIC-GLUT1(Flox/+), and NIC-GLUT1(Flox/Flox) mice. In addition, we evaluated effects of glucose restriction or GLUT1 inhibition on transformation in MCF10A-ERBB2 breast epithelial cells in three-dimensional culture. Finally, we utilized global gene expression profiling data of primary human breast tumors to determine the relationship between SLC2A1 and stage of tumorigenesis. All of the NIC-GLUT1(+/+) mice developed tumors in less than 200 days. In contrast, only 1 NIC-GLUT1(Flox/Flox) mouse and 1 NIC-GLUT1(Flox/+) mouse developed mammary tumors, even after 18 months. Mammary gland development was not disrupted in NIC mice lacking GLUT1; however, epithelial content of mature glands was reduced compared to NIC-GLUT1(Flox/+) mice. In MCF10A-ERBB2 cells, glucose restriction or GLUT1 inhibition blocked transformation induced by activated ERBB2 through reduced cell proliferation. In human breast cancers, SLC2A1 was higher in ductal carcinoma in situ compared to the normal breast, but lower in invasive versus in situ lesions, suggesting the requirement for GLUT1 decreases as tumors progress. This study demonstrates a strict requirement for GLUT1 in the early stages of

  17. FRACTAL DIMENSIONALITY ANALYSIS OF MAMMARY GLAND THERMOGRAMS

    Directory of Open Access Journals (Sweden)

    Yu. E. Lyah

    2016-06-01

    Full Text Available Thermography may enable early detection of a cancer tumour within a mammary gland at an early, treatable stage of the illness, but thermogram analysis methods must be developed to achieve this goal. This study analyses the feasibility of applying the Hurst exponent readings algorithm for evaluation of the high dimensionality fractals to reveal any possible difference between normal thermograms (NT and malignant thermograms (MT.

  18. Basisquamous Carcinoma

    Directory of Open Access Journals (Sweden)

    Yesudian Devakar P

    1997-01-01

    Full Text Available A 50 year old woman presented with an ulceroproliferative mass in the value of 4 month duration. Biopsy of the lesion showed features of a basisquamous cell carcinoma. This is a rare tumour showing histopathological features of both basal cell and squamous cell carcinomas. The clinical, histopathological and histogenetic status of this tumour are discussed.

  19. Oxytocin binding sites in bovine mammary tissue

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. The coexistence of atypical intraductal hyperplasias with breast carcinoma.

    Science.gov (United States)

    Bogdan, F; Gîrniţă, L; Florescu, M; Simionescu, C; Crăiţoiu, S; Comănescu, V

    1998-01-01

    We present a study made during 4 years (1992-1996), which pursued the underlining of the atypical intraductal hiperplasias (A.I.D.H.) lesions, met isolated or in the association with mamar carcinoma. Our study included a 188 number of the breast tumors, among: in the 23 cases we established the existence of the modification by the A.I.D.H, type at the fibrocystics disease associated or not with the other benign diseases of the breast (fibroadenosis, intraductal papiloma) and in the 63 cases there were the modification by the AIDH associated with in situ or invasiv carcinoma. Epithelial hyperplasia is frequently associated with the fibrocystic changes, being included in the category of fibrocystic or proliferating modifications. The synonymous terms used for the epithelial hyperplasia are the hiperplazia ductala, or the epitelioza, or the papilomatosis The last two are suggested by the proliferation possibility (papillary or linear) of the epithelial or the mio-epithelial cells. Regardless of the microscopic aspect of the lesion, that should be acknowledged and treated as it is, due to the increased risk of the development of a carcinoma later on, and also due to the ratio of association between the modification and the mammary carcinoma. The risk of occurrence of subsequent carcinoma is augmented in the presence of the epithelial atipii and also increases in the presence of a mammary carcinoma at the relatives of the first rank (1.3). In this context, the importance of the differential diagnosis between the simple intraductal hyperplasia and the atypical one, the difficulty of differentiation from intraductal carcinoma in some cases, and finally the association with an increased risk of subsequent occurrence of carcinoma, constitute into sufficient arguments to consider this topic separately.

  1. New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells.

    Science.gov (United States)

    Chang, Ted H-T; Kunasegaran, Kamini; Tarulli, Gerard A; De Silva, Duvini; Voorhoeve, P Mathijs; Pietersen, Alexandra M

    2014-01-07

    Parity-identified mammary epithelial cells (PI-MECs) are an interesting cellular subset because they survive involution and are a presumptive target for transformation by human epidermal growth factor receptor 2 (HER2)/neu in mammary tumors. Depending on the type of assay, PI-MECs have been designated lobule-restricted progenitors or multipotent stem/progenitor cells. PI-MECs were reported to be part of the basal population of mammary epithelium based on flow cytometry. We investigated the cellular identity and lineage potential of PI-MECs in intact mammary glands. We performed a quantitative and qualitative analysis of the contribution of PI-MECs to mammary epithelial cell lineages in pregnant and involuted mammary glands by immunohistochemistry, fluorescence-activated cells sorting (FACS), and quantitative polymerase chain reaction. PI-MECs were labeled by the activation of Whey Acidic Protein (WAP)-Cre during pregnancy that results in permanent expression of yellow fluorescent protein. After involution, PI-MECs are present exclusively in the luminal layer of mammary ducts. During pregnancy, PI-MECs contribute to the luminal layer but not the basal layer of alveolar lobules. Strikingly, whereas all luminal estrogen receptor (ER)-negative cells in an alveolus can be derived from PI-MECs, the alveolar ER-positive cells are unlabeled and reminiscent of Notch2-traced L cells. Notably, we observed a significant population of unlabeled alveolar progenitors that resemble PI-MECs based on transcriptional and histological analysis. Our demonstration that PI-MECs are luminal cells underscores that not only basal cells display multi-lineage potential in transplantation assays. However, the lineage potential of PI-MECs in unperturbed mammary glands is remarkably restricted to luminal ER-negative cells of the secretory alveolar lineage. The identification of an unlabeled but functionally similar population of luminal alveolar progenitor cells raises the question of whether PI

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2017-01-10

    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.

  4. Melatonin and mammary cancer: a short review.

    Science.gov (United States)

    Sánchez-Barceló, E J; Cos, S; Fernández, R; Mediavilla, M D

    2003-06-01

    Melatonin is an indolic hormone produced mainly by the pineal gland. The former hypothesis of its possible role in mammary cancer development was based on the evidence that melatonin down-regulates some of the pituitary and gonadal hormones that control mammary gland development and which are also responsible for the growth of hormone-dependent mammary tumors. Furthermore, melatonin could act directly on tumoral cells, as a naturally occurring antiestrogen, thereby influencing their proliferative rate. The first reports revealed a low plasmatic melatonin concentration in women with estrogen receptor (ER)-positive breast tumors. However, later studies on the possible role of melatonin on human breast cancer have been scarce and mostly of an epidemiological type. These studies described a low incidence of breast tumors in blind women as well as an inverse relationship between breast cancer incidence and the degree of visual impairment. Since light inhibits melatonin secretion, the relative increase in the melatonin circulating levels in women with a decreased light input could be interpreted as proof of the protective role of melatonin on mammary carcinogenesis. From in vivo studies on animal models of chemically induced mammary tumorigenesis, the general conclusion is that experimental manipulations activating the pineal gland or the administration of melatonin lengthens the latency and reduces the incidence and growth rate of mammary tumors, while pinealectomy usually has the opposite effects. Melatonin also reduces the incidence of spontaneous mammary tumors in different kinds of transgenic mice (c-neu and N-ras) and mice from strains with a high tumoral incidence. In vitro experiments, carried out with the ER-positive MCF-7 human breast cancer cells, demonstrated that melatonin, at a physiological concentration (1 nM) and in the presence of serum or estradiol: (a) inhibits, in a reversible way, cell proliferation, (b) increases the expression of p53 and p21WAF1

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier GmbH. All rights reserved.

  6. Mammary Gland Ontegeny and Neoplasia in Oxytocin Deficient Mice.

    Science.gov (United States)

    1998-07-01

    be protective. The technical objectives of this proposal as follows. 1) Determine the prevalence of mammary neoplasia in the progeny of MMTV-infected...WT mice to develop mammary neoplasia when exposed in vivo to ovarian steroid hormones. If oxytocin is shown to be an important factor in breast cancer, exogenous oxytocin may be a potential safe, non-toxic measure in its prevention.

  7. Identity and dynamics of mammary stem cells during branching morphogenesis

    NARCIS (Netherlands)

    Scheele, Colinda L.G.J.; Hannezo, Edouard; Muraro, Mauro J.; Zomer, Anoek; Langedijk, Nathalia S.M.; Van Oudenaarden, Alexander; Simons, Benjamin D; Van Rheenen, Jacco

    2017-01-01

    During puberty, the mouse mammary gland develops into a highly branched epithelial network. Owing to the absence of exclusive stem cell markers, the location, multiplicity, dynamics and fate of mammary stem cells (MaSCs), which drive branching morphogenesis, are unknown. Here we show that

  8. Induction of mammary gland tumor in female Sprague- Dawley rats ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-07-12

    Jul 12, 2010 ... hormone sensitivity and histology. There is no other animal tumor comparable to these models because of the similarity in the function and structure of certain rat mammary tumors to hormone-sensitive human breast cancer (Young and Hallowers, 1973). Mammary gland LA7 cells were isolated in 1979 ...

  9. Resident macrophages influence stem cell activity in the mammary gland

    NARCIS (Netherlands)

    Gyorki, D.E.; Asselin-Labat, M.L.; Rooijen, van N.; Lindeman, G.J.; Visvader, J.E.

    2009-01-01

    Introduction Macrophages in the mammary gland are essential for morphogenesis of the ductal epithelial tree and have been implicated in promoting breast tumor metastasis. Although it is well established that macrophages influence normal mammopoiesis, the mammary cell types that these accessory cells

  10. Infrared Thermography in Dogs with Mammary Tumors and Healthy Dogs.

    Science.gov (United States)

    Pavelski, M; Silva, D M; Leite, N C; Junior, D A; de Sousa, R S; Guérios, S D; Dornbusch, P T

    2015-01-01

    Infrared thermography is a painless, noninvasive, nonionizing diagnostic imaging exam used in human medicine as an auxiliary tool for breast cancer diagnosis in women. Define thermographic mean temperatures of healthy mammary glands and compare these temperatures with those of mammary glands with tumors in dogs. Fifty client-owned female dogs were evaluated, including 20 with histopathologically confirmed mammary tumor and 30 clinically healthy (control). A randomized study using infrared thermography analyzed each mammary gland of the animals from the control group and mammary glands with tumors from the tumor group, then the thermographic temperatures obtained were compared. Thermographic exam was performed in a temperature-controlled room with a cooled thermographic camera-Flir E-40 (Flir Systems(®) ) There was significantly a higher temperature in the caudal abdominal and inguinal mammary glands than the other glands in the healthy group (P < .05). Dogs with mammary tumors had significantly higher thermographic temperature compared with unaffected glands regardless of the tumor size and the location (P < .05). The technique seems to be able to assess for the presence of neoplasia within the mammary tissue in bitches. Further investigation is necessary to determine the impact of this technique when adopted clinically. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  11. Lactating Vulva Mammary Tissue in a Nigerian | Igwegbe | Nigerian ...

    African Journals Online (AJOL)

    ... cystic mass in the right labium majus that developed rapidly in the early puerperium following her 5th confinement. Histology of the completely excised cyst revealed a secretory mammary tissue. There was no recurrence ten months after surgery while breastfeeding. Key Words: lactation, vulva, Mammary tissue, Nigerian

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

    Science.gov (United States)

    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 ...

  13. Macrophages Mediate a Switch between Canonical and Non-Canonical Wnt Pathways in Canine Mammary Tumors

    Science.gov (United States)

    Król, Magdalena; Mucha, Joanna; Majchrzak, Kinga; Homa, Agata; Bulkowska, Małgorzata; Majewska, Alicja; Gajewska, Małgorzata; Pietrzak, Marta; Perszko, Mikołaj; Romanowska, Karolina; Pawłowski, Karol; Manuali, Elisabetta; Hellmen, Eva; Motyl, Tomasz

    2014-01-01

    Objective According to the current hypothesis, tumor-associated macrophages (TAMs) are “corrupted” by cancer cells and subsequently facilitate, rather than inhibit, tumor metastasis. Because the molecular mechanisms of cancer cell–TAM interactions are complicated and controversial we aimed to better define this phenomenon. Methods and Results Using microRNA microarrays, Real-time qPCR and Western blot we showed that co-culture of canine mammary tumor cells with TAMs or treatment with macrophage-conditioned medium inhibited the canonical Wnt pathway and activated the non-canonical Wnt pathway in tumor cells. We also showed that co-culture of TAMs with tumor cells increased expression of canonical Wnt inhibitors in TAMs. Subsequently, we demonstrated macrophage-induced invasive growth patterns and epithelial–mesenchymal transition of tumor cells. Validation of these results in canine mammary carcinoma tissues (n = 50) and xenograft tumors indicated the activation of non-canonical and canonical Wnt pathways in metastatic tumors and non-metastatic malignancies, respectively. Activation of non-canonical Wnt pathway correlated with number of TAMs. Conclusions We demonstrated that TAMs mediate a “switch” between canonical and non-canonical Wnt signaling pathways in canine mammary tumors, leading to increased tumor invasion and metastasis. Interestingly, similar changes in neoplastic cells were observed in the presence of macrophage-conditioned medium or live macrophages. These observations indicate that rather than being “corrupted” by cancer cells, TAMs constitutively secrete canonical Wnt inhibitors that decrease tumor proliferation and development, but as a side effect, they induce the non-canonical Wnt pathway, which leads to tumor metastasis. These data challenge the conventional understanding of TAM–cancer cell interactions. PMID:24404146

  14. Age Modifies the Effect of 2-MeV Fast Neutrons on Rat Mammary Carcinogenesis.

    Science.gov (United States)

    Imaoka, Tatsuhiko; Nishimura, Mayumi; Daino, Kazuhiro; Hosoki, Ayaka; Takabatake, Masaru; Kokubo, Toshiaki; Doi, Kazutaka; Showler, Kaye; Nishimura, Yukiko; Moriyama, Hitomi; Morioka, Takamitsu; Shimada, Yoshiya; Kakinuma, Shizuko

    2017-10-01

    The relative biological effectiveness (RBE) of neutrons depends on their physical nature (e.g., energy) and the biological context (e.g., end points, materials). From the perspective of radiological protection, age is an important biological context that influences radiation-related cancer risk, but very few studies have addressed its potential impact on neutron effects. We therefore investigated the influence of age on the effect of accelerator-generated fast neutrons (mean energy, ∼2 MeV) in an animal model of breast carcinogenesis. Female Sprague-Dawley rats at 1, 3 and 7 weeks of age were irradiated with fast neutrons at absorbed doses of 0.0485-0.97 Gy. All animals were kept under specific pathogen-free conditions and screened weekly for mammary tumors by palpation until they were 90 weeks old. Tumors were diagnosed based on histology. Mathematical modeling was used to analyze mammary cancer incidence, collectively using data from this study and a previously reported experiment on 137Cs gamma rays. The results indicate that neutron irradiation elevated the risk of palpable mammary carcinoma with a linear dose response, the slope of which depended on age at time of irradiation. The RBE of neutron radiation was 7.5 ± 3.4, 9.3 ± 3.5 and 26.1 ± 8.9 (mean ± SE) for animals exposed at 1, 3 and 7 weeks of age, respectively. Our results indicate that age of the animal is an important factor influencing the effect of fast neutrons on breast cancer risk.

  15. Normal mammary fibroblasts induce reversion of the malignant phenotype in human primary breast cancer.

    Science.gov (United States)

    Römer, Anna-Maria; Lühr, Inke; Klein, Andreas; Friedl, Andreas; Sebens, Susanne; Rösel, Frank; Arnold, Norbert; Strauss, Alexander; Jonat, Walter; Bauer, Maret

    2013-04-01

    The tumor microenvironment plays a major role in tumor growth and progression. Its manipulation can lead to a reversion of the malignant phenotype. Here we explored the ability of normal mammary fibroblasts (HMFs) to induce reversion of the malignant phenotype of primary breast carcinoma cells (PBCs) in a three-dimensional (3D) context. PBCs were isolated from 13 primary breast carcinomas and cultured in 3D collagen-I gels as mono- or co-culture with HMFs. In five co-cultures, PBCs exhibited reversion of their malignant phenotype, whereas PBCs in matched monocultures exhibited disorganized growth. Reversion, defined as the restoration of the complete baso-apical polarity axis, was confirmed with established polarity markers. Secretion of the tissue-specific glycoprotein MAM-6 into the acinar lumens and deposition of basement membrane indicated functional differentiation. Gene expression analysis revealed a set of differentially regulated genes which possibly affect the reversion process. These included MAL, ELF5, MAP6, ZMYND11 and SQLE. These findings highlight the significant role of fibroblasts in regulating the carcinoma phenotype.

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

    Science.gov (United States)

    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.

  17. Huntingtin Regulates Mammary Stem Cell Division and Differentiation

    Directory of Open Access Journals (Sweden)

    Salah Elias

    2014-04-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  19. GALLBLADDER CARCINOMA

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    Blaž Trotovšek

    2003-12-01

    Full Text Available Background. Carcinoma of the gallbladder is a tumour with a dismal prognosis and 5-years overall survival rate less than 5%. Among the tumours of the gastrointestinal tract it is fifth in the row and its incidence is approximately 1.2/105. Tumour occurs more often (2–6 times in women and in people over 50 years old (90%. According to the Slovenian Registry of Cancer for year 1998 the incidence of gallbladder carcinoma was 2.7/105 and it occurred 4 times more often among women. The most important risk factors for development of gallbladder carcinoma are: bile stones, chronic inflammation and polyps of the gallbladder. Carcinoma of the gallbladder develops in only 2–3% of the patients with bile stones. When discovered, carcinoma has already invaded the liver in 60%, regional lymph nodes in 45% and the other surrounding organs in 40%. Carcinoma is at time of diagnosis already disseminated in distant organs in 20%. Only in 10% of the patients it is confined to the gallbladder wall. Before the routine use of the ultrasound, computed tomography and tumour markers the disease was discovered preoperatively in 10% versus 90% today. Diagnostic percutaneous biopsy is not recommended. TNM classification and staging of the disease is important for the decision of the modality of treatment.Conclusions. For TNM stage I gallbladder carcinoma, simple cholecystectomy is sufficient. When stage II-IVa is discovered, »en block« resection of gallbladder, liver segments 4b and 5, common bile duct and thorough lymphadenectomy is recommended. Regional radiotherapy and intraarterial chemotherapy with Mitomycin-C are showing promising results. Longterm outcome in patients with gallbladder carcinoma is improving but it is still disappointing.

  20. Tracheal Carcinoma

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    Ashok K Chauhan

    2012-01-01

    Full Text Available Adenoid cystic carcinoma of the trachea is a rare primary tracheal malignancy. Obstructive symptoms such as dyspnoea, hoarseness of voice, dysphasia are commonly seen symptoms. Combined modality treatments including surgery and radiation therapy are considered as optimal treatment for these tumours. A case of adenoid cystic carcinoma in a 35 years old male patient who was treated successfully by surgical excision and external beam radiation therapy is presented.

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

    Directory of Open Access Journals (Sweden)

    Marion eBoutinaud

    2015-10-01

    Full Text Available 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 analysing 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.

  2. Mammary gland tumors in a male Cocker Spaniel.

    Science.gov (United States)

    Kwon, Soon-Chan; Yoo, Dae-Young; Ko, Minho; Lee, Kwon-Young; Kwak, Ho-Hyun; Park, In-Chul; Hwang, In-Koo; Choi, Jung-Hoon; Chung, Jin-Young

    2017-04-11

    Mammary gland tumors are the most common tumors in sexually intact female dogs; however, they are rare in male dogs. This study was conducted to investigate the relationship between sexual hormones and mammary gland tumors in a male dog. A 13-year-old, intact male Cocker Spaniel presented to the Veterinary Teaching Hospital of Kangwon National University, Republic of Korea, with an acute right ruptured caudal abdominal mass. Physical examination revealed a 14 × 14 cm ruptured mass in the right caudal abdomen, as well as a 1.5 × 1.5 cm mass in the first right mammary gland. The estrogen and progesterone concentrations in serum were within normal levels. Total mastectomy was done on the right side mammary glands. Following surgery, the site was fully recovered; however, a mass that had grown to 2 × 2 cm was found in the left fifth mammary gland and a testis tumor was also found over the period of 4 months. Mastectomy was performed on the left caudal mammary gland and castration was also performed. After the final surgery, the dog fully recovered. Histopathological examination of all three masses revealed high grade mammary adenocarcinoma in the mammary gland and the testis was diagnosed as Leydig cell adenoma. Immunohistochemical analysis revealed that the estrogen and progesterone receptors were expressed on limited cells in mammary and testis tumors. The results of this study suggest that mammary tumors and testes tumors can occur in male dogs without relationship to female sexual hormone.

  3. Genetic mechanisms in Apc-mediated mammary tumorigenesis.

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    Mari Kuraguchi

    2009-02-01

    Full Text Available Many components of Wnt/beta-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 beta-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; Apc(CKO/+ 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 beta-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.

  4. Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells.

    Science.gov (United States)

    Nguyen, Long V; Pellacani, Davide; Lefort, Sylvain; Kannan, Nagarajan; Osako, Tomo; Makarem, Maisam; Cox, Claire L; Kennedy, William; Beer, Philip; Carles, Annaick; Moksa, Michelle; Bilenky, Misha; Balani, Sneha; Babovic, Sonja; Sun, Ivan; Rosin, Miriam; Aparicio, Samuel; Hirst, Martin; Eaves, Connie J

    2015-12-10

    Most human breast cancers have diversified genomically and biologically by the time they become clinically evident. Early events involved in their genesis and the cellular context in which these events occur have thus been difficult to characterize. Here we present the first formal evidence of the shared and independent ability of basal cells and luminal progenitors, isolated from normal human mammary tissue and transduced with a single oncogene (KRAS(G12D)), to produce serially transplantable, polyclonal, invasive ductal carcinomas within 8 weeks of being introduced either subrenally or subcutaneously into immunodeficient mice. DNA barcoding of the initial cells revealed a dramatic change in the numbers and sizes of clones generated from them within 2 weeks, and the first appearance of many 'new' clones in tumours passaged into secondary recipients. Both primary and secondary tumours were phenotypically heterogeneous and primary tumours were categorized transcriptionally as 'normal-like'. This system challenges previous concepts that carcinogenesis in normal human epithelia is necessarily a slow process requiring the acquisition of multiple driver mutations. It also presents the first description of initial events that accompany the genesis and evolution of malignant human mammary cell populations, thereby contributing new understanding of the rapidity with which heterogeneity in their properties can develop.

  5. Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation

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    Hai Hu

    2016-07-01

    Full Text Available Whether the human tumor virus, Epstein–Barr Virus (EBV, promotes breast cancer remains controversial and a potential mechanism has remained elusive. Here we show that EBV can infect primary mammary epithelial cells (MECs that express the receptor CD21. EBV infection leads to the expansion of early MEC progenitor cells with a stem cell phenotype, activates MET signaling and enforces a differentiation block. When MECs were implanted as xenografts, EBV infection cooperated with activated Ras and accelerated the formation of breast cancer. Infection in EBV-related tumors was of a latency type II pattern, similar to nasopharyngeal carcinoma (NPC. A human gene expression signature for MECs infected with EBV, termed EBVness, was associated with high grade, estrogen-receptor-negative status, p53 mutation and poor survival. In 11/33 EBVness-positive tumors, EBV-DNA was detected by fluorescent in situ hybridization for the viral LMP1 and BXLF2 genes. In an analysis of the TCGA breast cancer data EBVness correlated with the presence of the APOBEC mutational signature. We conclude that a contribution of EBV to breast cancer etiology is plausible, through a mechanism in which EBV infection predisposes mammary epithelial cells to malignant transformation, but is no longer required once malignant transformation has occurred.

  6. Analysis of Contractility and Invasion Potential of Two Canine Mammary Tumor Cell Lines

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    Kaisa Rajakylä

    2017-09-01

    Full Text Available Cancer cells are surrounded by a mechanically and biochemically distinct microenvironment that undergoes dynamic changes throughout the neoplastic progression. During this progression, some cancer cells acquire abnormal characteristics that potentiate their escape from the primary tumor site, to establish secondary tumors in distant organs. Recent studies with several human cancer cell lines have shown that the altered physical properties of tumor cells, such as their ability to apply high traction forces to the surroundings, are directly linked with their potential to invade and metastasize. To test the hypothetical interconnection between actomyosin-mediated traction forces and invasion potential within 3D-microenvironment, we utilized two canine mammary tumor cell lines with different contractile properties. These cell lines, canine mammary tumor (CMT-U27 and CMT-U309, were found to have distinct expression patterns of lineage-specific markers and organization of actin-based structures. In particular, CMT-U309 carcinoma cells were typified by thick contractile actomyosin bundles that exerted high forces to their environment, as measured by traction force microscopy. These high contractile forces also correlated with the prominent invasiveness of the CMT-U309 cell line. Furthermore, we found high contractility and 3D-invasion potential to be dependent on the activity of 5′AMP-activated protein kinase (AMPK, as blocking AMPK signaling was found to reverse both of these features. Taken together, our findings implicate that actomyosin forces correlate with the invasion potential of the studied cell lines.

  7. Dimethyl-Benz(aanthracene: A mammary carcinogen and a neuroendocrine disruptor

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    Bernard Kerdelhué

    2016-12-01

    Full Text Available Polycyclic Aromatic Hydrocarbons (PAHs are potent carcinogens. Among these, dimethylbenz(aanthracene (DMBA is well known for its capacity to induce mammary carcinomas in female Sprague-Dawley (SD rats. Ovariectomy suppresses the susceptibility of this model to DMBA, thus suggesting that the inducible action of the carcinogen depends on ovarian hormones. The promotion of DMBA-induced adenocarcinoma is accompanied by a series of neuroendocrine disruptions of both Hypothalamo-Pituitary-Gonadal (HPG and Hypothalamo-Pituitary-Adrenal (HPA axes and of the secretion of melatonin during the latency period of 2 months that precedes the occurrence of the first mammary tumor. The present review analyses the various neuroendocrine disruptions that occur along the HPG and the HPA axes, and the marked inhibitory effect of the carcinogen on melatonin secretion. The possible relationships between the neuroendocrine disruptions, which essentially consist in an increased pre-ovulatory secretion of 17β-estradiol and prolactin, associated with a marked reduction of melatonin secretion, and the decrease in gene expression of the receptors for aryl-hydrocarbons receptor (AhR and 17β-estradiol (ERα; ERβ are also discussed.

  8. Analysis of Contractility and Invasion Potential of Two Canine Mammary Tumor Cell Lines.

    Science.gov (United States)

    Rajakylä, Kaisa; Krishnan, Ramaswamy; Tojkander, Sari

    2017-01-01

    Cancer cells are surrounded by a mechanically and biochemically distinct microenvironment that undergoes dynamic changes throughout the neoplastic progression. During this progression, some cancer cells acquire abnormal characteristics that potentiate their escape from the primary tumor site, to establish secondary tumors in distant organs. Recent studies with several human cancer cell lines have shown that the altered physical properties of tumor cells, such as their ability to apply high traction forces to the surroundings, are directly linked with their potential to invade and metastasize. To test the hypothetical interconnection between actomyosin-mediated traction forces and invasion potential within 3D-microenvironment, we utilized two canine mammary tumor cell lines with different contractile properties. These cell lines, canine mammary tumor (CMT)-U27 and CMT-U309, were found to have distinct expression patterns of lineage-specific markers and organization of actin-based structures. In particular, CMT-U309 carcinoma cells were typified by thick contractile actomyosin bundles that exerted high forces to their environment, as measured by traction force microscopy. These high contractile forces also correlated with the prominent invasiveness of the CMT-U309 cell line. Furthermore, we found high contractility and 3D-invasion potential to be dependent on the activity of 5'AMP-activated protein kinase (AMPK), as blocking AMPK signaling was found to reverse both of these features. Taken together, our findings implicate that actomyosin forces correlate with the invasion potential of the studied cell lines.

  9. Undifferentiated salivary gland carcinomas

    DEFF Research Database (Denmark)

    Herbst, H.; Hamilton-Dutoit, S.; Jakel, K.T.

    2004-01-01

    malignant lymphomas, amelanotic melanomas, Merkel cell carcinomas, and adenoid cystic carcinomas, in particular in small biopsy materials. Because of the rarity of undifferentiated salivary gland carcinomas, the differential diagnosis should always include metastases of undifferentiated carcinomas arising...

  10. Development of mammary glands of fat sheep submitted to restricted feeding during late pregnancy

    DEFF Research Database (Denmark)

    Nørgaard, J V; Nielsen, M O; Theil, P K

    2008-01-01

    Mammary gland development in sheep occurs mainly during puberty and pregnancy. We have investigated the effects of a late gestation feed restriction on mammary gland development in sheep.......Mammary gland development in sheep occurs mainly during puberty and pregnancy. We have investigated the effects of a late gestation feed restriction on mammary gland development in sheep....

  11. Mammary gland pathologies in the parturient buffalo

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    G N Purohit

    2014-12-01

    Full Text Available Parturition related mammary gland pathologies in the buffalo appear to be low on accord of anatomic (longer teat length, thicker streak canal and physiologic (lower cisternal storage of secreted milk, lower milk production differences with cattle. Hemolactia, udder edema and hypogalactia usually occur in the buffalo due to physiologic changes around parturition however mastitis involves pathologic changes in the udder and teats; the incidence of mastitis is however lower compared to cattle. The incidence and therapy of hemolactia, udder edema and hypogalactia are mentioned and the risk factors, incidence, diagnosis, therapy and prevention for mastitis in buffalo are also described.

  12. Changes in the Structure of the Thymus under Conditions of Various Treatments for Experimental Mammary Tumor.

    Science.gov (United States)

    Kazakov, O V; Kabakov, A V; Poveshchenko, A F; Ishchenko, I Yu; Poveshchenko, O V; Strunkin, D N; Raiter, T V; Michurina, S V; Konenkov, V I

    2017-03-01

    Morphological changes in the thymus of female Wistar rats with experimental mammary gland carcinomas were studied. After adjuvant therapy, the area of the cortical matter and density of parenchymal cells in the thymus decreased, while areas of the medulla, connective tissue, and content of immunoblasts and macrophages increased. In the thymuses of rats receiving exogenous DNA, morphological signs of activation of the lymphoid and epithelial components were found: areas of the cortex and medulla, glandular and connective tissue corresponded to the values in intact animals, the counts of lymphocytes in the central part of the cortical matter and of macrophages in all zones of the thymus increased, and lymphocyte migration from the thymus increased (in comparison with the chemotherapy group).

  13. Survival analysis of female dogs with mammary tumors after mastectomy: epidemiological, clinical and morphological aspects

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    Maria Luíza de M. Dias

    2016-03-01

    Full Text Available Abstract: Mammary gland tumors are the most common type of tumors in bitches but research on survival time after diagnosis is scarce. The purpose of this study was to investigate the relationship between survival time after mastectomy and a number of clinical and morphological variables. Data was collected retrospectively on bitches with mammary tumors seen at the Small Animal Surgery Clinic Service at the University of Brasília. All subjects had undergone mastectomy. Survival analysis was conducted using Cox's proportional hazard method. Of the 139 subjects analyzed, 68 died and 71 survived until the end of the study (64 months. Mean age was 11.76 years (SD=2.71, 53.84% were small dogs. 76.92% of the tumors were malignant, and 65.73% had both thoracic and inguinal glands affected. Survival time in months was associated with age (hazard rate ratios [HRR] =1.23, p-value =1.4x10-4, animal size (HRR between giant and small animals =2.61, p-value =0.02, nodule size (HRR =1.09, p-value =0.03, histological type (HRR between solid carcinoma and carcinoma in a mixed tumor =2.40, p-value =0.02, time between diagnosis and surgery (TDS, with HRR =1.21, p-value =2.7x10-15, and the interaction TDS*follow-up time (HRR =0.98, p-value =1.6x10-11. The present study is one of the few on the subject matter. Several important covariates were evaluated and age, animal size, nodule size, histological type, TDS and TDS*follow up time were identified as significantly associated to survival time.

  14. Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bishayee, Anupam, E-mail: abishayee@auhs.edu [Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA 90755 (United States); Mandal, Animesh [Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272 (United States)

    2014-10-15

    Highlights: • Dietary administration of an ethanolic extract of aerial parts of T. portulacastrum (TPE) exhibits a striking chemopreventive effect in an experimentally induced classical animal model of breast cancer. • The mammary tumor-inhibitory effect of TPE could be achieved, at least in part, though intervention of key hallmark capabilities of tumor cells, such as abnormal cell proliferation and evasion of apoptosis. • TPE is capable of diminishing activated canonical Wnt/β-catenin signaling to exhibit antiproliferative, proapoptotic and oncostatic effects during this early-stage mammary carcinoma. • These results coupled with a safety profile of T. portulacastrum may encourage further studies to understand the full potential of this dietary plant for chemoprevention of breast cancer. - Abstract: Due to limited treatment options for advanced-stage metastatic breast cancer, a high priority should be given to develop non-toxic chemopreventive drugs. The value of various natural and dietary agents to reduce the risk of developing breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a dietary and medicinal plant, has been found to exert antihepatotoxic and antihepatocarcinogenic properties in rodents. This study was initiated to investigate mechanism-based chemopreventive potential of an ethanolic extract of T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary gland carcinogenesis, an experimental tumor model that closely resembles human breast cancer. Rats had access to a basal diet supplemented with TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden and average tumor weight

  15. Salivary gland-like breast carcinomas: An infrequent disease.

    Science.gov (United States)

    Sherwell-Cabello, Santiago; Maffuz-Aziz, Antonio; Ríos-Luna, Nina Paola; Bautista-Piña, Verónica; Rodríguez-Cuevas, Sergio

    2016-11-01

    To show the incidence, as well as the clinical and histopathological characteristics, of patients diagnosed with mammary salivary gland-like carcinomas at our institution. A retrospective study was conducted in all women diagnosed with breast cancer at our institution from January 2005 to February 2016. Patients with diagnosis of salivary gland-like breast carcinomas were included. In this period, 6384 patients were diagnosed with breast cancer at our institution; salivary gland-like carcinomas were found in 7 patients (0.1%), adenoid cystic carcinoma was diagnosed in 5 patients (0.07%), acinic cell carcinoma in 1 patient (0.015%) and mucoepidermoid carcinoma in 1 patient (0.015%). The triple-negative subtype was found in all of the tumors. Median follow-up was 66.3 months (range, 1-108 months). No patient developed local or distant recurrence. Salivary gland-like breast tumors are extremely rare. We found a global incidence of 0.1%. Adenoid cystic, acinic cell and mucoepidermoid carcinomas were the three histologic types diagnosed. Although the triple-negative subtype is mainly found, good prognosis is expected. Copyright © 2016 Elsevier GmbH. All rights reserved.

  16. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Shuxian Jiang

    2010-03-01

    Full Text Available Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo.To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo.Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate.

  17. Progesterone induces adult mammary stem cell expansion.

    Science.gov (United States)

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

    2010-06-10

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

  18. Disruption of reelin signaling alters mammary gland morphogenesis

    Science.gov (United States)

    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

  19. Exploring the gain of function contribution of AKT to mammary tumorigenesis in mouse models.

    Directory of Open Access Journals (Sweden)

    Carmen Blanco-Aparicio

    Full Text Available Elevated expression of AKT has been noted in a significant percentage of primary human breast cancers, mainly as a consequence of the PTEN/PI3K pathway deregulation. To investigate the mechanistic basis of the AKT gain of function-dependent mechanisms of breast tumorigenesis, we explored the phenotype induced by activated AKT transgenes in a quantitative manner. We generated several transgenic mice lines expressing different levels of constitutively active AKT in the mammary gland. We thoroughly analyzed the preneoplastic and neoplastic mammary lesions of these mice and correlated the process of tumorigenesis to AKT levels. Finally, we analyzed the impact that a possible senescent checkpoint might have in the tumor promotion inhibition observed, crossing these lines to mammary specific p53(R172H mutant expression, and to p27 knock-out mice. We analyzed the benign, premalignant and malignant lesions extensively by pathology and at molecular level analysing the expression of proteins involved in the PI3K/AKT pathway and in cellular senescence. Our findings revealed an increased preneoplastic phenotype depending upon AKT signaling which was not altered by p27 or p53 loss. However, p53 inactivation by R172H point mutation combined with myrAKT transgenic expression significantly increased the percentage and size of mammary carcinoma observed, but was not sufficient to promote full penetrance of the tumorigenic phenotype. Molecular analysis suggest that tumors from double myrAKT;p53(R172H mice result from acceleration of initiated p53(R172H tumors and not from bypass of AKT-induced oncogenic senescence. Our work suggests that tumors are not the consequence of the bypass of senescence in MIN. We also show that AKT-induced oncogenic senescence is dependent of pRb but not of p53. Finally, our work also suggests that the cooperation observed between mutant p53 and activated AKT is due to AKT-induced acceleration of mutant p53-induced tumors. Finally, our

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

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    Manuali Elisabetta

    2012-06-01

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

  1. Anti-growth action on mouse mammary and prostate glands of a monoclonal antibody to prolactin receptor.

    Science.gov (United States)

    Sissom, J F; Eigenbrodt, M L; Porter, J C

    1988-12-01

    Monoclonal antibody (PrR-7A) against purified PRL receptor was used in the following studies. When PRL receptor was chromatographed on affinity columns containing PrR-7A antibody or monoclonal antibody against hemocyanin, which served as a control, PRL receptor was bound to the column containing PrR-7A antibody, but not to the column containing control antibody. When solubilized PRL receptor was incubated with PrR-7A antibody, the specific binding of the receptor was reduced 52%. Female mice were treated with the carcinogen, 7,12-dimethylbenz[a]anthracene, and during the succeeding 48 weeks were treated weekly with PrR-7A antibody or control antibody. In the control group 13% developed mammary carcinomas, and 16% developed moderate-to-severe intraductal hyperplasia. No mammary carcinomas were found in the mice treated with PrR-7A antibody, and only 8% of the mice had moderate-to-severe intraductal hyperplasia. Male mice made hyperprolactinemic by implanted pituitary glands were treated weekly with PrR-7A or control antibody. After 7 weeks of treatment, the mean weight of the prostates of mice treated with PrR-7A antibody was 8 +/- 1.1 mg (mean +/- SE), and that of mice treated with control antibody was 27 +/- 3.6 mg. Similar differences were seen in the protein and DNA content of the prostates. These results indicate that PrR-7A antibody is directed against PRL receptor and that immunization with this antibody reduces the incidence of PRL-dependent mammary tumors and preneoplastic ductal hyperplasia and prevents PRL-induced hyperplasia of the prostate.

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

    Science.gov (United States)

    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

  3. Mammary remodeling in primiparous and multiparous dairy goats during lactation

    DEFF Research Database (Denmark)

    Safayi, Sina; Theil, Peter Kappel; Elbrønd, Vibeke Sødring

    2010-01-01

    obtained from both mammary glands of 3 PP and 6 MP (≥2 parity) dairy goats at parturition (d 1), d 10, 60, and 180 of lactation. Gene transcription relating to MEC turnover and vascular function was quantified by real-time reverse transcription-PCR, mammary morphology was characterized (quantitative......Milk production is generally lower but lactation persistency higher in primiparous (PP) than in multiparous (MP) goats. This may be related to differences in development and maintenance of mammary gland function, but the underlying mechanisms are not well understood. The present study aimed...

  4. Suitability of tissue prints for immunocytochemical diagnosis of mammary cancer.

    Science.gov (United States)

    Surowiak, P; Dziegiel, P; Zabel, M; Zasławski, R

    2001-01-01

    The present study was aimed at evaluating suitability of tissue prints for immunocytochemical evaluation of mammary cancer cells. The prints, originating from 30 cases of mammary cancer were studied using immunocytochemical reactions with monoclonal antibodies against estrogen and progesterone receptors, metallothionein (MT), P-glycoprotein and cytokeratins (clone LP34). Expression of individual antigens was assessed using the scale in which intensity of the colour reaction and percentage of positive cells were taken into account. The obtained results did not differ qualitatively or quantitatively from those obtained in paraffin sections. The studies have shown that tissue prints can be used for reliable immunocytochemical evaluation of expression of various proteins in mammary cancer cells.

  5. Mammary artery harvesting using the Da Vinci Si robotic system

    Directory of Open Access Journals (Sweden)

    Leonardo Secchin Canale

    2014-03-01

    Full Text Available Internal mammary artery harvesting is an essential part of any coronary artery bypass operation. Totally endoscopic coronary artery bypass graft surgery has become reality in many centers as a safe and effective alternative to conventional surgery in selected patients. Internal mammary artery harvesting is the initial part of the procedure and should be performed equally safely if one wants to achieve excellence in patency rates for the bypass. We here describe the technique for mammary harvesting with the Da Vinci Si robotic system.

  6. Mammary artery harvesting using the Da Vinci Si robotic system

    Science.gov (United States)

    Canale, Leonardo Secchin; Bonatti, Johannes

    2014-01-01

    Internal mammary artery harvesting is an essential part of any coronary artery bypass operation. Totally endoscopic coronary artery bypass graft surgery has become reality in many centers as a safe and effective alternative to conventional surgery in selected patients. Internal mammary artery harvesting is the initial part of the procedure and should be performed equally safely if one wants to achieve excellence in patency rates for the bypass. We here describe the technique for mammary harvesting with the Da Vinci Si robotic system. PMID:24896171

  7. Delivering the message: epimorphin and mammary epithelial morphogenesis.

    Science.gov (United States)

    Radisky, Derek C; Hirai, Yohei; Bissell, Mina J

    2003-08-01

    The mammary gland consists of a highly branched tubular epithelium surrounded by a complex mesenchymal stroma. Epimorphin is an extracellular protein that is expressed by mammary mesenchymal cells that directs epithelial morphogenesis. Depending upon the context of presentation--polar versus apolar--epimorphin can selectively direct two key processes of tubulogenesis: branching morphogenesis (processes involved in tubule initiation and extension) and luminal morphogenesis (required for enlargement of tubule caliber). Here, we outline the fundamentals of mammary gland development and describe the function of epimorphin in these processes. We conclude with a review of recent studies that suggest similar morphogenic roles for epimorphin in other glandular organs.

  8. Ameloblastic carcinoma

    Directory of Open Access Journals (Sweden)

    Praveen B Kumar

    2009-01-01

    Full Text Available Ameloblastoma of jaws are common and locally destructive tumors originating from odontogenic apparatus. They constitute approximately 1% of all jaw tumors with 80% occurring in the mandible. Ameloblastoma exhibiting a frank malignancy is a rare entity and occurs in less than 1% of all ameloblastomas. Among the two jaws, ameloblastic carcinoma involving maxilla is extremely rare with only few cases reported so far in the literature. Here we report two cases of ameloblastic carcinoma one involving the maxilla and the other involving mandible, with an aggressive clinical course leading to extensive local destruction of the affected jaws.

  9. Stromal and Epithelial Caveolin-1 Both Confer a Protective Effect Against Mammary Hyperplasia and Tumorigenesis : Caveolin-1 Antagonizes Cyclin D1 Function in Mammary Epithelial Cells

    OpenAIRE

    Williams, Terence M.; Sotgia, Federica; Lee, Hyangkyu; Hassan, Ghada; Di Vizio, Dolores; Bonuccelli, Gloria; Capozza, Franco; Mercier, Isabelle; Rui, Hallgeir; Pestell, Richard G.; Lisanti, Michael P.

    2006-01-01

    Here, we investigate the role of caveolin-1 (Cav-1) in breast cancer onset and progression, with a focus on epithelial-stromal interactions, ie, the tumor microenvironment. Cav-1 is highly expressed in adipocytes and is abundant in mammary fat pads (stroma), but it remains unknown whether loss of Cav-1 within mammary stromal cells affects the differentiated state of mammary epithelia via paracrine signaling. To address this issue, we characterized the development of the mammary ductal system ...

  10. Hormone Receptor Expression Analyses in Neoplastic and Non-Neoplastic Canine Mammary Tissue by a Bead Based Multiplex Branched DNA Assay: A Gene Expression Study in Fresh Frozen and Formalin-Fixed, Paraffin-Embedded Samples.

    Directory of Open Access Journals (Sweden)

    Annika Mohr

    Full Text Available Immunohistochemistry (IHC is currently considered the method of choice for steroid hormone receptor status evaluation in human breast cancer and, therefore, it is commonly utilized for assessing canine mammary tumors. In case of low hormone receptor expression, IHC is limited and thus is complemented by molecular analyses. In the present study, a multiplex bDNA assay was evaluated as a method for hormone receptor gene expression detection in canine mammary tissues. Estrogen receptor (ESR1, progesterone receptor (PGR, prolactin receptor (PRLR and growth hormone receptor (GHR gene expressions were evaluated in neoplastic and non-neoplastic canine mammary tissues. A set of 119 fresh frozen and 180 formalin-fixed, paraffin-embedded (FFPE was comparatively analyzed and used for assay evaluation. Furthermore, a possible association between the hormone receptor expression in different histological subtypes of canine malignant mammary tumors and the castration status, breed and invasive growth of the tumor were analyzed. The multiplex bDNA assay proved to be more sensitive for fresh frozen specimens. Hormone receptor expression found was significantly decreased in malignant mammary tumors in comparison to non-neoplastic tissue and benign mammary tumors. Among the histological subtypes the lowest gene expression levels of ESR1, PGR and PRLR were found in solid, anaplastic and ductal carcinomas. In summary, the evaluation showed that the measurement of hormone receptors with the multiplex bDNA assay represents a practicable method for obtaining detailed quantitative information about gene expression in canine mammary tissue for future studies. Still, comparison with IHC or quantitative real-time PCR is needed for further validation of the present method.

  11. Activating Transcription Factor-5 Knockdown Reduces Aggressiveness of Mammary Tumor Cells and Attenuates Mammary Tumor Growth

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    Sarit Ben-Shmuel

    2017-07-01

    Full Text Available Activating transcription factor-5 (ATF5 is an anti-apoptotic factor and has been implicated in enhancing the survival of cancer cells under stress and in regulating the autophagy process. Targeting ATF5 in anticancer therapy may be particularly attractive because of its differential role in cancer cells than in non-transformed cells, thus allowing specificity of the treatment. Using the delivery of short hairpin RNA vectors into the Mvt1 and Met1 cell lines, we tested the role of ATF5 in the development of mammary tumors in vivo and in regulating proliferation and migration of these cells in vitro. In this study, we demonstrate that knockdown of ATF5 (ATF5-KD in both cell lines results in a decreased tumor volume and weight, as well as in a reduced proliferation rate and migratory potential of the cells. In addition, ATF5-KD led to an increased autophagy flux and a shift in the sub-populations comprising Mvt1 cells from the aggressive CD24-positive cells toward less aggressive CD24-negative cells. Taken together, these findings suggest that ATF5 plays an important role in enhancing mammary tumor cells overall aggressiveness and in promoting mammary tumor growth and emphasize the possible benefit of anti-ATF5 therapy in breast cancer patients, particularly, against tumors characterized with the positive expression of cell surface CD24.

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

    Science.gov (United States)

    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. Carcinoma vulvar

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    Yamit Peñas Zayas

    2015-11-01

    Full Text Available El carcinoma de la vulva tiene una incidencia de aproximadamente un 3-5% dentro de todas las enfermedades ginecológicas malignas. El 90% de los tumores malignos de la vulva está constituido por carcinoma epidermoide, el resto son adenocarcinomas, carcinomas de células basales y melanomas. Se realiza la presentación de un caso de una paciente femenina de 25 años de edad con antecedentes  de Diabetes Mellitus tipo II y trombopatia, que ingresa en el servicio de ginecología con un cuadro cutáneo polimorfo, localizado en labios mayores y menores, dado por lesiones eritematoerosivas y vegetante, sospechándose clínicamente el diagnóstico  de un carcinoma epidermoide, corroborándose el mismo histológicamente al realizarse biopsia de piel. Se indicó tratamiento con quimioterapia. Por la edad de la paciente y ser menos frecuente en mucosa que en la piel,  motivo la presentación del caso.

  14. Parathyroid carcinoma

    DEFF Research Database (Denmark)

    Qvist, N; Krøll, L; Ladefoged, C

    1986-01-01

    Parathyroid carcinoma is a slow growing tumor, and the patients most often die from complications to the hypercalcemia. Therefore, any attempt should be made to remove local recurrence and metastasis surgically, as medical treatment is disappointing. A case treated with extensive vascular surgery...

  15. Nasopharyngeal carcinoma

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    Brennan Bernadette

    2006-06-01

    Full Text Available Abstract Nasopharyngeal carcinoma (NPC is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx. The annual incidence of NPC in the UK is 0.3 per million at age 0–14 years, and 1 to 2 per million at age 15–19 years. Incidence is higher in the Chinese and Tunisian populations. Although rare, NPC accounts for about one third of childhood nasopharyngeal neoplasms. Three subtypes of NPC are recognized in the World Health Organization (WHO classification: 1 squamous cell carcinoma, typically found in the older adult population; 2 non-keratinizing carcinoma; 3 undifferentiated carcinoma. The tumor can extend within or out of the nasopharynx to the other lateral wall and/or posterosuperiorly to the base of the skull or the palate, nasal cavity or oropharynx. It then typically metastases to cervical lymph nodes. Cervical lymphadenopathy is the initial presentation in many patients, and the diagnosis of NPC is often made by lymph node biopsy. Symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis of the soft palate, hearing loss and cranial nerve palsies. Larger growths may produce nasal obstruction or bleeding and a "nasal twang". Etiological factors include Epstein-Barr virus (EBV, genetic susceptibility and consumption of food with possible carcinogens – volatile nitrosamines. The recommended treatment schedule consists of three courses of neoadjuvant chemotherapy, irradiation, and adjuvant interferon (IFN-beta therapy.

  16. Laryngeal carcinoma

    African Journals Online (AJOL)

    Biological pharyngo-cutaneous fistula could not. One patient died markers of alcohol abuse in patients with from a ruptured carotid following radiotherapy three carcinoma of the larynx. Acta months after surgery, while the remaining eight are still. Otorrinolaringol Esp 1998 Aug- doing well with an average duration of follow ...

  17. Chemoprevention of Radiation Induced Rat Mammary Neoplasms

    Science.gov (United States)

    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

  18. Activation status of Wnt/ß-catenin signaling in normal and neoplastic breast tissues: relationship to HER2/neu expression in human and mouse.

    Directory of Open Access Journals (Sweden)

    Sara Khalil

    Full Text Available Wnt/ß-catenin signaling is strongly implicated in neoplasia, but the role of this pathway in human breast cancer has been controversial. Here, we examined Wnt/ß-catenin pathway activation as a function of breast cancer progression, and tested for a relationship with HER2/neu expression, using a human tissue microarray comprising benign breast tissues, ductal carcinoma in situ (DCIS, and invasive carcinomas. Cores were scored for membranous ß-catenin, a key functional component of adherens junctions, and for nucleocytoplasmic ß-catenin, a hallmark of Wnt/ß-catenin pathway activation. Only 82% of benign samples exhibited membrane-associated ß-catenin, indicating a finite frequency of false-negative staining. The frequency of membrane positivity was similar in DCIS samples, but was significantly reduced in carcinomas (45%, P<0.001, consistent with loss of adherens junctions during acquisition of invasiveness. Negative membrane status in cancers correlated with higher grade (P = 0.04 and estrogen receptor-negative status (P = 0.03, both indices of poor prognosis. Unexpectedly, a substantial frequency of nucleocytoplasmic ß-catenin was observed in benign breast tissues (36%, similar to that in carcinomas (35%. Positive-staining basal nuclei observed in benign breast may identify putative stem cells. An increased frequency of nucleocytoplasmic ß-catenin was observed in DCIS tumors (56%, suggesting that pathway activation may be an early event in human breast neoplasia. A correlation was observed between HER2/neu expression and nucleocytoplasmic ß-catenin in node-positive carcinomas (P = 0.02. Furthermore, cytoplasmic ß-catenin was detected in HER2/neu-induced mouse mammary tumors. The Axin2(NLSlacZ mouse strain, a previously validated reporter of mammary Wnt/ß-catenin signaling, was utilized to define in vivo transcriptional consequences of HER2/neu-induced ß-catenin accumulation. Discrete hyperplastic foci observed in mammary

  19. Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli

    Science.gov (United States)

    Blum, Shlomo E.; Heller, Elimelech D.; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

    2015-01-01

    Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study

  20. Conserved and variable: Understanding mammary stem cells across species.

    Science.gov (United States)

    Rauner, Gat; Ledet, Melissa M; Van de Walle, Gerlinde R

    2018-01-01

    Postnatal mammary gland development requires the presence of mammary stem and progenitor cells (MaSC), which give rise to functional milk-secreting cells and regenerate the mammary epithelium with each cycle of lactation. These long-lived, tissue-resident MaSC are also targets for malignant transformation and may be cancer cells-of-origin. Consequently, MaSC are extensively researched in relation to their role and function in development, tissue regeneration, lactation, and breast cancer. The basic structure and function of the mammary gland are conserved among all mammalian species, from the most primitive to the most evolved. However, species vary greatly in their lactation strategies and mammary cancer incidence, making MaSC an interesting focus for comparative research. MaSC have been characterized in mice, to a lesser degree in humans, and to an even lesser degree in few additional mammals. They remain uncharacterized in most mammalian species, including "ancient" monotremes, marsupials, wild, and rare species, as well as in common and domestic species such as cats. Identification and comparison of MaSC across a large variety of species, particularly those with extreme lactational adaptations or low mammary cancer incidence, is expected to deepen our understanding of development and malignancy in the mammary gland. Here, we review the current status of MaSC characterization across species, and underline species variations in lactation and mammary cancer through which we may learn about the role of MaSC in these processes. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  1. Delivering the message: epimorphin and mammary epithelial morphogenesis☆

    OpenAIRE

    Radisky, Derek C.; Hirai, Yohei; Bissell, Mina J.

    2003-01-01

    The mammary gland consists of a highly branched tubular epithelium surrounded by a complex mesenchymal stroma. Epimorphin is an extracellular protein that is expressed by mammary mesenchymal cells that directs epithelial morphogenesis. Depending upon the context of presentation – polar versus apolar – epimorphin can selectively direct two key processes of tubulogenesis: branching morphogenesis (processes involved in tubule initiation and extension) and luminal morphogenesis (required for enla...

  2. Semaphorin7A promotes tumor growth and exerts a pro-angiogenic effect in macrophages of mammary tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Ramon eGarcia-Areas

    2014-02-01

    Full Text Available Semaphorins, a large family of molecules involved in the axonal guidance and development of the nervous system, have been recently shown to have both angiogenic and anti-angiogenic properties. Specifically, semaphorin 7A (SEMA7A has been reported to have a chemotactic activity in neurogenesis, and to be an immune modulator via it binding to α1β1integrins. Additionally, SEMA7A has been shown to promote chemotaxis of monocytes, inducing them to produce proinflammatory mediators. In this study we explored the role of SEMA7A in the tumoral context. We show that SEMA7A is highly expressed by DA-3 murine mammary tumor cells in comparison to normal mammary cells (EpH4, and that peritoneal macrophages from mammary tumor-bearing mice also express SEMA7A at higher levels compared to peritoneal macrophages derived from normal control mice. We also show that murine macrophages treated with recombinant murine SEMA7A significantly increased their expression of proangiogenic molecules, such as CXCL2/MIP-2. Gene silencing of SEMA7A in peritoneal elicited macrophages from DA-3 tumor-bearing mice resulted in decreased CXCL2 expression. Mice implanted with SEMA7A silenced tumor cells showed decreased angiogenesis in the tumors compared to the wild type tumors. Furthermore, peritoneal elicited macrophages from mice bearing SEMA7A-silenced tumors produce significantly (p< 0.01 lower levels of angiogenic proteins, such as MIP-2, CXCL1 and MMP-9, compared to macrophages from control DA-3 mammary tumors. We postulate that SEMA7A derived from mammary carcinomas may serve as a monocyte chemoattractant and skew monocytes into a pro-tumorigenic phenotype. A putative relationship between tumor-derived SEMA7A and monocytes could prove valuable in establishing new research avenues towards unraveling important tumor-host immune interactions in breast cancer patients.

  3. Down-regulation of the zinc-finger homeobox protein TSHZ2 releases GLI1 from the nuclear repressor complex to restore its transcriptional activity during mammary tumorigenesis

    Science.gov (United States)

    Riku, Miho; Inaguma, Shingo; Ito, Hideaki; Tsunoda, Takumi; Ikeda, Hiroshi; Kasai, Kenji

    2016-01-01

    Although breast cancer is one of the most common malignancies, the molecular mechanisms underlying its development and progression are not fully understood. To identify key molecules involved, we screened publicly available microarray datasets for genes differentially expressed between breast cancers and normal mammary glands. We found that three of the genes predicted in this analysis were differentially expressed among human mammary tissues and cell lines. Of these genes, we focused on the role of the zinc-finger homeobox protein TSHZ2, which is down-regulated in breast cancer cells. We found that TSHZ2 is a nuclear protein harboring a bipartite nuclear localization signal, and we confirmed its function as a C-terminal binding protein (CtBP)-dependent transcriptional repressor. Through comprehensive screening, we identified TSHZ2-suppressing genes such as AEBP1 and CXCR4, which are conversely up-regulated by GLI1, the downstream transcription factor of Hedgehog signaling. We found that GLI1 forms a ternary complex with CtBP2 in the presence of TSHZ2 and that the transcriptional activity of GLI1 is suppressed by TSHZ2 in a CtBP-dependent manner. Indeed, knockdown of TSHZ2 increases the expression of AEBP1 and CXCR4 in TSHZ2-expressing immortalized mammary duct epithelium. Concordantly, immunohistochemical staining of mammary glands revealed that normal duct cells expresses GLI1 in the nucleus along with TSHZ2 and CtBP2, whereas invasive ductal carcinoma cells, which does not express TSHZ2, show the increase in the expression of AEBP1 and CXCR4 and in the cytoplasmic localization of GLI1. Thus, we propose that down-regulation of TSHZ2 is crucial for mammary tumorigenesis via the activation of GLI1. PMID:26744317

  4. Immunohistochemistry in ocular carcinomas.

    Science.gov (United States)

    Sramek, Brett; Lisle, Allison; Loy, Timothy

    2008-07-01

    The distinction between ocular sebaceous carcinoma, poorly differentiated ocular squamous cell carcinoma and ocular basal cell carcinoma can be challenging. An appropriate immunohistochemical panel may help to differentiate these lesions. To determine the distribution and use of several immunostains in these specimens, formalin-fixed, paraffin-embedded tissue from several of each was studied using an immunohistochemical technique. Positive staining for cytokeratin (CK)7 was seen in 100% of sebaceous carcinomas, 77.8% of basal cell carcinomas and 67.7% of squamous cell carcinomas. One hundred percent of sebaceous and basal cell carcinomas were positive for cytokeratin CAM 5.2, while only 83.3% of squamous cell carcinomas were positive. Using epithelial membrane antigen (EMA), 100% of squamous cell carcinomas and 80% of sebaceous carcinomas were positive, while basal cell carcinomas were uniformly negative. One hundred percent of basal cell carcinomas and 80% of sebaceous carcinomas were positive for Ber-EP4, while all squamous cell carcinomas were negative. Finally, 77.8%, 20% and 16.7% of basal cell carcinomas, sebaceous carcinomas and squamous cell carcinomas showed immunoreactivity for the androgen receptor. An EMA positive, Ber-EP4 positive immunophenotype supports sebaceous carcinoma, EMA positive, Ber-EP4 negative result supports squamous cell carcinoma and an EMA negative, Ber-EP4 positive result supports basal cell carcinoma.

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

    Science.gov (United States)

    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. © 2013 by the American College of Nurse-Midwives.

  6. Coagulogram of the 35 females dogs with mammary neoplasias

    Directory of Open Access Journals (Sweden)

    Cristina Rauen Ribas

    2015-03-01

    Full Text Available ABSTRACT. Ribas C.R., Dornbusch P.T., de Faria M.R., Cirio S.M. & Wouk A.F.P. de F. [Coagulogram of the 35 females dogs with mammary neoplasias.] Coagulograma de 35 cadelas com neoplasias mamárias. Revista Brasileira de Medicina Veterinária, 37(1:83-87, 2015. Departamento de Medicina Veteriná- ria, Universidade Federal do Paraná, Rua dos Funcionários 1540, Curitiba, PR, 80035-050, Brasil. E-mail: ribas-cr@bol.com.br The mammary neoplasias are easily noticed by the owners, and are increasingly on the rise due to greater longevity of animals in recent years. So often cater to large number of female dogs in routine clinical medical oncology in small animals. Epidemiologically, the mammary neoplasias affecting mainly older dogs not spayed or neutered after several heats, with no racial predisposition. However, hardly possible to report laboratory findings directly or indirectly related to the neoplastic process. Therefore, the aim of this study was to analyze the coagulation of 36 dogs suffering from mammary cancer, diagnosed clinically and confirmed histopathologically. It was possible to identify changes such as decrease of TTPA (activated partial thromboplastin time, thrombocytosis, thrombocytopenia, disseminated intravascular coagulation (DIC. It was concluded that the alterations in coagulation of female dogs with mammary neoplasms were more significant in dogs suffering from mammary tumors in stage V.

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

    Science.gov (United States)

    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.

  8. Embryology of the Mammary glands (Breast)

    African Journals Online (AJOL)

    Dr. Sunday

    Department of Pathology, A. B. U. Teaching Hospital, Zaria. Request for Reprints to Dr. Adewuyi, S. A.Radiotherapy and Oncology Center,. A. B. U. Teaching Hospital, Shika – Zaria P. M. B. 1008. E-mail: sadewuyi2003@yahoo.com. Abstract. Objectives:: To evaluate the pattern of skeletal metastases from breast carcinoma ...

  9. Mouse mammary tumor virus-like gene sequences are present in lung patient specimens

    Directory of Open Access Journals (Sweden)

    Rodríguez-Padilla Cristina

    2011-09-01

    Full Text Available Abstract Background Previous studies have reported on the presence of Murine Mammary Tumor Virus (MMTV-like gene sequences in human cancer tissue specimens. Here, we search for MMTV-like gene sequences in lung diseases including carcinomas specimens from a Mexican population. This study was based on our previous study reporting that the INER51 lung cancer cell line, from a pleural effusion of a Mexican patient, contains MMTV-like env gene sequences. Results The MMTV-like env gene sequences have been detected in three out of 18 specimens studied, by PCR using a specific set of MMTV-like primers. The three identified MMTV-like gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and 97% homologous, respectively, as compared to GenBank sequence accession number AY161347. The INER6 and HZ-101 samples were isolated from lung cancer specimens, and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two of the env sequences exhibited disruption of the reading frame due to mutations. Conclusion In summary, we identified the presence of MMTV-like gene sequences in 2 out of 11 (18% of the lung carcinomas and 1 out of 7 (14% of acute inflamatory lung infiltrate specimens studied of a Mexican Population.

  10. 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice

    National Research Council Canada - National Science Library

    Chunxia Chen; Zhihuan Nong; Qiuqiao Xie; Junhui He; Wene Cai; Xiuneng Tang; Xiaoyu Chen; Renbin Huang; Ying Gao

    2017-01-01

    ...) remarkably inhibited the growth of human breast cancer cells with little toxicity. In this study, we investigated the toxicity and efficacy of DMDD to treat metastatic breast tumors using an in vivo mouse model of the 4T1 mammary carcinoma...

  11. α-Mangostin extracted from the pericarp of the mangosteen (Garcinia mangostana Linn reduces tumor growth and lymph node metastasis in an immunocompetent xenograft model of metastatic mammary cancer carrying a p53 mutation

    Directory of Open Access Journals (Sweden)

    Okuno Yasushi

    2011-06-01

    Full Text Available Abstract Background The mangosteen fruit has a long history of medicinal use in Chinese and Ayurvedic medicine. Recently, the compound α-mangostin, which is isolated from the pericarp of the fruit, was shown to induce cell death in various types of cancer cells in in vitro studies. This led us to investigate the antitumor growth and antimetastatic activities of α-mangostin in an immunocompetent xenograft model of mouse metastatic mammary cancer having a p53 mutation that induces a metastatic spectrum similar to that seen in human breast cancers. Methods Mammary tumors, induced by inoculation of BALB/c mice syngeneic with metastatic BJMC3879luc2 cells, were subsequently treated with α-mangostin at 0, 10 and 20 mg/kg/day using mini-osmotic pumps and histopathologically examined. To investigate the mechanisms of antitumor ability by α-mangostin, in vitro studies were also conducted. Results Not only were in vivo survival rates significantly higher in the 20 mg/kg/day α-mangostin group versus controls, but both tumor volume and the multiplicity of lymph node metastases were significantly suppressed. Apoptotic levels were significantly increased in the mammary tumors of mice receiving 20 mg/kg/day and were associated with increased expression of active caspase-3 and -9. Other significant effects noted at this dose level were decreased microvessel density and lower numbers of dilated lymphatic vessels containing intraluminal tumor cells in mammary carcinoma tissues. In vitro, α-mangostin induced mitochondria-mediated apoptosis and G1-phase arrest and S-phase suppression in the cell cycle. Since activation by Akt phosphorylation plays a central role in a variety of oncogenic processes, including cell proliferation, anti-apoptotic cell death, angiogenesis and metastasis, we also investigated alterations in Akt phosphorylation induced by α-mangostin treatment both in vitro and in vivo. Quantitative analysis and immunohistochemistry showed that

  12. α-Mangostin extracted from the pericarp of the mangosteen (Garcinia mangostana Linn) reduces tumor growth and lymph node metastasis in an immunocompetent xenograft model of metastatic mammary cancer carrying a p53 mutation.

    Science.gov (United States)

    Shibata, Masa-Aki; Iinuma, Munekazu; Morimoto, Junji; Kurose, Hitomi; Akamatsu, Kanako; Okuno, Yasushi; Akao, Yukihiro; Otsuki, Yoshinori

    2011-06-03

    The mangosteen fruit has a long history of medicinal use in Chinese and Ayurvedic medicine. Recently, the compound α-mangostin, which is isolated from the pericarp of the fruit, was shown to induce cell death in various types of cancer cells in in vitro studies. This led us to investigate the antitumor growth and antimetastatic activities of α-mangostin in an immunocompetent xenograft model of mouse metastatic mammary cancer having a p53 mutation that induces a metastatic spectrum similar to that seen in human breast cancers. Mammary tumors, induced by inoculation of BALB/c mice syngeneic with metastatic BJMC3879luc2 cells, were subsequently treated with α-mangostin at 0, 10 and 20 mg/kg/day using mini-osmotic pumps and histopathologically examined. To investigate the mechanisms of antitumor ability by α-mangostin, in vitro studies were also conducted. Not only were in vivo survival rates significantly higher in the 20 mg/kg/day α-mangostin group versus controls, but both tumor volume and the multiplicity of lymph node metastases were significantly suppressed. Apoptotic levels were significantly increased in the mammary tumors of mice receiving 20 mg/kg/day and were associated with increased expression of active caspase-3 and -9. Other significant effects noted at this dose level were decreased microvessel density and lower numbers of dilated lymphatic vessels containing intraluminal tumor cells in mammary carcinoma tissues. In vitro, α-mangostin induced mitochondria-mediated apoptosis and G1-phase arrest and S-phase suppression in the cell cycle. Since activation by Akt phosphorylation plays a central role in a variety of oncogenic processes, including cell proliferation, anti-apoptotic cell death, angiogenesis and metastasis, we also investigated alterations in Akt phosphorylation induced by α-mangostin treatment both in vitro and in vivo. Quantitative analysis and immunohistochemistry showed that α-mangostin significantly decreased the levels of phospho

  13. Evaluation of blood T-lymphocyte subpopulations involved in host cellular immunity in dogs with mammary cancer.

    Science.gov (United States)

    Karayannopoulou, Maria; Anagnostou, Tilemachos; Margariti, Apostolia; Kostakis, Charalampos; Kritsepi-Konstantinou, Maria; Psalla, Dimitra; Savvas, Ioannis

    2017-04-01

    Cancer-bearing patients are often immunosuppressed. In dogs with mammary or other cancers, various alterations in blood cell populations involved in host cellular immunity have been reported; among these cell populations some T-lymphocyte subsets play an important role against cancer. The purpose of the present study was to investigate any alterations in circulating T-lymphocyte subpopulations involved in cellular immunity in bitches with mammary cancer, in comparison to age-matched healthy intact bitches. Twenty eight dogs with mammary cancer and 14 control dogs were included in this study. Twelve out of the 28 bitches had mammary cancer of clinical stage II and 16/28 of stage III. Histological examination revealed that 23/28 animals had carcinomas, 3/28 sarcomas and 2/28 carcinosarcomas. White blood cell, neutrophil and lymphocyte absolute numbers were measured by complete blood count. Furthermore, blood T-lymphocyte population (CD3(+)) and the subpopulations CD4(+), CD8(+) and CD5(low+) were assessed by flow cytometry. White blood cell and neutrophil but not lymphocyte absolute numbers were higher (P=0.003 and P=0.001, respectively) in cancer patients than controls. Flow cytometric analysis revealed that the relative percentage of T-lymphocytes (CD3(+)) and of CD4(+), CD8(+) subpopulations was lower (the CD4(+)/CD8(+) ratio was higher), whereas the percentage of CD5(low+) T-cells was higher, in dogs with cancer compared to controls; however, a statistically significant difference was found only in the case of CD8(+) T-cells (P=0.014), whereas in the case of the CD4(+)/CD8(+) ratio the difference almost reached statistical significance (P=0.059). Based on these findings, it can be suggested that, although the absolute number of blood lymphocytes is unchanged, the relative percentages of T-lymphocyte subpopulations involved in host cell-mediated immunity are altered, but only cytotoxic CD8(+) T-cells are significantly suppressed, in dogs with mammary cancer of

  14. Thyroid cancer - medullary carcinoma

    Science.gov (United States)

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. ... and adults. Unlike other types of thyroid cancer, MTC is less ...

  15. Concurrent breast stroma sarcoma and breast carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Carvalho Teresa

    2010-12-01

    Full Text Available Abstract Introduction Breast cancer is one of the most important health problems in the world and affects a great number of women over the entire globe. This group of tumors rarely presents as bilateral disease and, when it does happen, normally occurs within the same histological type. We report a rare case of concurrent bilateral breast cancer with two different histology types, a breast carcinoma and a breast sarcoma, in a 42-year-old woman referred to our hospital. Case presentation A 42-year-old Caucasian woman admitted to our institute in August 1999, presented with a nodule in the left breast of 3.0 × 2.5 cm, and, in the right breast, one of 1.0 cm, suspected of malignancy and with a clinically negative armpit. Biopsies had revealed invasive mammary carcinoma (right breast and sarcoma (left breast. She was submitted to bilateral modified radical mastectomy. A histological study showed an invasive mammary carcinoma degree II lobular pleomorphic type with invasion of seven of the 19 excised axillary nodes in the right breast and, in the left breast, a sarcoma of the mammary stroma, for which the immunohistochemistry study was negative for epithelial biomarkers and positive for vimentin. Later, she was submitted for chemotherapy (six cycles of 75 mg/m2 5-fluorouracil, epirubicin and cyclophosphamide followed by radiotherapy of the thoracic wall and axillary nodes on the left. Hormone receptors were positive in the tumor of the right breast, and tamoxifen, 20 mg, was prescribed on a daily basis (five years followed by letrozole, 2.5 mg, also daily (five years. She presented no sign of negative evolution in the last consultation. Conclusion The risk of development of bilateral breast cancer is about 1% each year within a similar histological type, but it is higher in tumors with lobular histology. In this case, the patient presented, simultaneously, two histologically distinct tumors, thus evidencing a rare situation.

  16. Incidental detection of filarial worm in metastatic axillary lymph node from ductal carcinoma breast

    Directory of Open Access Journals (Sweden)

    Ranjan Agrawal

    2015-01-01

    Full Text Available Filariasis is a major disease of the tropics. Frequently, lymphatics of the lower limbs, retroperitoneal tissues, spermatic cord, epididymis, and mammary glands are involved. Simultaneous filariasis along with another underlying disease is rare. We present a rare case of filariasis of the axillary lymph node in a modified radical mastectomy specimen, which also showed metastatic deposits of ductal carcinoma breast. The case is presented due to its rarity.

  17. Antineoplastic effects of clove buds (Syzygium aromaticum L.) in the model of breast carcinoma.

    Science.gov (United States)

    Kubatka, Peter; Uramova, Sona; Kello, Martin; Kajo, Karol; Kruzliak, Peter; Mojzis, Jan; Vybohova, Desanka; Adamkov, Marian; Jasek, Karina; Lasabova, Zora; Zubor, Pavol; Fialova, Silvia; Dokupilova, Svetlana; Solar, Peter; Pec, Martin; Adamicova, Katarina; Danko, Jan; Adamek, Mariusz; Busselberg, Dietrich

    2017-11-01

    It is supposed that plant functional foods, rich in phytochemicals, may potentially have preventive effects in carcinogenesis. In this study, the anticancer effects of cloves in the in vivo and in vitro mammary carcinoma model were assessed. Dried flower buds of cloves (CLOs) were used at two concentrations of 0.1% and 1% through diet during 13 weeks after the application of chemocarcinogen. After autopsy, histopathological and immunohistochemical analyses of rat mammary carcinomas were performed. Moreover, in vitro evaluation using MCF-7 cells was carried out. Dietary administered CLO caused the dose-dependent decrease in tumour frequency by 47.5% and 58.5% when compared to control. Analysis of carcinoma cells in animals showed bcl-2, Ki67, VEGFA, CD24 and CD44 expression decrease and Bax, caspase-3 and ALDH1 expression increase after high-dose CLO administration. MDA levels were substantially decreased in rat carcinomas in both CLO groups. The evaluation of histone modifications revealed increase in lysine trimethylations and acetylations (H4K20me3, H4K16ac) in carcinomas after CLO administration. TIMP3 promoter methylation levels of CpG3, CpG4, CpG5 islands were altered in treated cancer cells. An increase in total RASSF1A promoter methylation (three CpG sites) in CLO 1 group was found. In vitro studies showed antiproliferative and pro-apoptotic effects of CLO extract in MCF-7 cells (analyses of cytotoxicity, Brdu, cell cycle, annexin V/PI, caspase-7, Bcl-2 and mitochondrial membrane potential). This study showed a significant anticancer effect of clove buds in the mammary carcinoma model in vivo and in vitro. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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

    Science.gov (United States)

    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; Karantza, Vassiliki; Chen, Suzie

    2015-05-01

    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

  19. Mammary Malignant Ulcer after Radiotherapy: Unpleasant Surprise.

    Science.gov (United States)

    Vindigni, Vincenzo; Kohlscheen, Eva; Kraljic, Tajna; Bassetto, Franco; Pavan, Chiara

    2017-04-01

    We present a case of a woman, 79 years old, followed by Psychiatry for depressive episodes after breast cancer removal. She was operated on for ductal breast carcinoma in 1983. Afterward she was submitted to adjuvant radiotherapy. She came to our attention for a chronic skin ulcer that developed into the radio-treated area about 4 years ago. We performed a skin biopsy and programed adipose tissue grafts to promote wound healing. The result of the biopsy was unexpected: dermal localization of not differentiated breast carcinoma. She is currently under systemic chemotherapy treatment. The key message is to always perform a skin biopsy of a chronic skin ulcer developed after breast cancer removal before planning surgical reconstruction.

  20. The Role of SnoN and Ski in Mammary Epithelial Cell Transformation

    National Research Council Canada - National Science Library

    Pan, Deng

    2007-01-01

    .... Higher level of Ski/SnoN is found in transformed mammary epithelial cells. Ski/SnoN might play a role in regulation of the transformation of mammary epithelial cell by antagonizing TGF signaling pathway...

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

    National Research Council Canada - National Science Library

    Nagy, Tamas

    2007-01-01

    ...) deletion in mammary-specific polyoma middle-T transgenic mice. We monitored mammary carcinogenesis in positive control (FAKFlox/Flox; MMTV-PyVT) and target (FAKFlox/Flox; MMTV-Cre; MMTV-PyVT) females...

  2. Mechanisms Underlying the Very High Susceptibility of the Immature Mammary Gland to Carcinogenic Initiation

    National Research Council Canada - National Science Library

    Gould, Michael

    2000-01-01

    The overall goal of this project was to explore the toxic effects of physical and chemical carcinogens on the immature mammary gland as compared to the effects on the young adult mammary gland using a rat model. We have: I...

  3. The Role of Phosphatidylinositol 3' -OH Kinase Signaling in Mammary Tumorigenesis

    National Research Council Canada - National Science Library

    Hutchinson, John

    2001-01-01

    ...) and its downstream targets such as the Akt kinase in the induction of mammary tumors. To assess the role of Akt in mammary development and tumorigenesis, we have generated transgenic mice that express an activated Akt (Akt-DD...

  4. The Role of Phosphatidylinositol 3' -OH Kinase Signaling in Mammary Tumorigenesis

    National Research Council Canada - National Science Library

    Hutchinson, John

    2002-01-01

    ...) and its downstream target Akt kinase in the induction of mammary tumors. To assess the role of Akt in mammary development and tumorigenesis, we generated transgenic mice that express an activated Akt (Akt-DD...

  5. ErbB3 drives mammary epithelial survival and differentiation during pregnancy and lactation

    National Research Council Canada - National Science Library

    Michelle M Williams; David B Vaught; Meghan Morrison Joly; Donna J Hicks; Violeta Sanchez; Philip Owens; Bushra Rahman; David L Elion; Justin M Balko; Rebecca S Cook

    2017-01-01

    ...) signaling, contributes to lactogenic expansion of the mammary gland. Methods We assessed mRNA expression levels by expression microarray of mouse mammary glands harvested throughout pregnancy and lactation...

  6. Multidisciplinary Biomarkers of Early Mammary Carcinogenesis

    Science.gov (United States)

    2011-04-01

    oxidation-reduction (redox) reactions in cells to generate energy in the form of adenosine triphosphate (ATP) are the conversion of nicotinamide ...photodynamic iagnosis of cancer of the bladder, brain, and skin , but has nly been approved for use on skin by the Food and Drug dministration in the...Gastrointest. Endosc. 491, 1–5 1999. 27. R. Na, I. Stender, and H. Wulf, “Can autofluorescence demarcate basal cell carcinoma from normal skin ? A comparison

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

    Science.gov (United States)

    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

  8. HISTOLOGICAL STUDY OF HUMAN MAMMARY GLAND IN WOMEN OF NORTH EASTERN REGION OF INDIA

    Directory of Open Access Journals (Sweden)

    Santona

    2015-09-01

    Full Text Available INTRODUCTION: The “mamma” or “breast” is a modified, ectodermal, glandular structure located in the superficial fascia of the anterior chest wall. In female they are evolved to secrete milk for the nourishment of their offspring. They are also present in a rudimentary form in males. MATERIALS AND METHODS: After obtaining institutional ethical clearance t he specimens of human mammary gland were divided into two groups i.e. reproductive (14 to 49 and post - menopausal (50 and above age. The specimens of both the age group were collected from fresh unembalmed human cadaver. The slides were prepared using the standard laboratory procedure. Stained slides were studied for different structures of the mammary gland such as the glandular structures, ducts and myoepithelial cells. Diameters of the ducts were measured in both age groups. The data were analyzed to ca lculate the mean and ‘t’ test was applied to find out the significant difference between mean values. RESULTS: The average diameter of the lactiferous duct as measured by micrometer scale was 2.0 mm and 0.83 mm in reproductive and post - menopausal age group respectively. Calculated value of t’= 4.68. d. f. (degree of freedom =18, P <0.01. Therefore the diameter of lactiferous duct between reproductive and postmenopausal age group differs significantly. DISCUSSION: The results obtained in this study are comp ared with the available established findings of other workers to draw a definite conclusion in the histomorphological aspect of reproductive and postmenopausal age group. CONCLUSION: Though different generations of sophisticated investigations such as mole cular level studies have evolved for the early detection of breast carcinoma, the knowledge of the normal developmental histological changes is most important which will help to detect early abnormal changes of the breast if any

  9. A targeted constitutive mutation in the APC tumor suppressor gene underlies mammary but not intestinal tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Claudia Gaspar

    2009-07-01

    Full Text Available Germline mutations in the adenomatous polyposis coli (APC gene are responsible for familial adenomatous polyposis (FAP, an autosomal dominant hereditary predisposition to the development of multiple colorectal adenomas and of a broad spectrum of extra-intestinal tumors. Moreover, somatic APC mutations play a rate-limiting and initiating role in the majority of sporadic colorectal cancers. Notwithstanding its multifunctional nature, the main tumor suppressing activity of the APC gene resides in its ability to regulate Wnt/beta-catenin signaling. Notably, genotype-phenotype correlations have been established at the APC gene between the length and stability of the truncated proteins encoded by different mutant alleles, the corresponding levels of Wnt/beta-catenin signaling activity they encode for, and the incidence and distribution of intestinal and extra-intestinal tumors. Here, we report a novel mouse model, Apc1572T, obtained by targeting a truncated mutation at codon 1572 in the endogenous Apc gene. This hypomorphic mutant allele results in intermediate levels of Wnt/beta-catenin signaling activation when compared with other Apc mutations associated with multifocal intestinal tumors. Notwithstanding the constitutive nature of the mutation, Apc(+/1572T mice have no predisposition to intestinal cancer but develop multifocal mammary adenocarcinomas and subsequent pulmonary metastases in both genders. The histology of the Apc1572T primary mammary tumours is highly heterogeneous with luminal, myoepithelial, and squamous lineages and is reminiscent of metaplastic carcinoma of the breast in humans. The striking phenotype of Apc(+/1572T mice suggests that specific dosages of Wnt/beta-catenin signaling activity differentially affect tissue homeostasis and initiate tumorigenesis in an organ-specific fashion.

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

    Directory of Open Access Journals (Sweden)

    Sara Caceres

    Full Text Available 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

  11. Antibody-Guided In Vivo Imaging for Early Detection of Mammary Gland Tumors

    Directory of Open Access Journals (Sweden)

    Laura Jeffords Moore

    2016-08-01

    Full Text Available BACKGROUND: Earlier detection of transformed cells using target-specific imaging techniques holds great promise. We have developed TAB 004, a monoclonal antibody highly specific to a protein sequence accessible in the tumor form of MUC1 (tMUC1. We present data assessing both the specificity and sensitivity of TAB 004 in vitro and in genetically engineered mice in vivo. METHODS: Polyoma Middle T Antigen mice were crossed to the human MUC1.Tg mice to generate MMT mice. In MMT mice, mammary gland hyperplasia is observed between 6 and 10 weeks of age that progresses to ductal carcinoma in situ by 12 to 14 weeks and adenocarcinoma by 18 to 24 weeks. Approximately 40% of these mice develop metastasis to the lung and other organs with a tumor evolution that closely mimics human breast cancer progression. Tumor progression was monitored in MMT mice (from ages 8 to 22 weeks by in vivo imaging following retro-orbital injections of the TAB 004 conjugated to indocyanine green (TAB-ICG. At euthanasia, mammary gland tumors and normal epithelial tissues were collected for further analyses. RESULTS: In vivo imaging following TAB-ICG injection permitted significantly earlier detection of tumors compared with physical examination. Furthermore, TAB-ICG administration in MMT mice enabled the detection of lung metastases while sparing recognition of normal epithelia. CONCLUSIONS: The data highlight the specificity and the sensitivity of the TAB 004 antibody in differentiating normal versus tumor form of MUC1 and its utility as a targeted imaging agent for early detection, tumor monitoring response, as well as potential clinical use for targeted drug delivery.

  12. Mammary remodeling in primiparous and multiparous dairy goats during lactation.

    Science.gov (United States)

    Safayi, S; Theil, P K; Elbrønd, V S; Hou, L; Engbaek, M; Nørgaard, J V; Sejrsen, K; Nielsen, M O

    2010-04-01

    Milk production is generally lower but lactation persistency higher in primiparous (PP) than in multiparous (MP) goats. This may be related to differences in development and maintenance of mammary gland function, but the underlying mechanisms are not well understood. The present study aimed to elucidate whether differences in lactational performance between PP and MP mammary glands are related to the time course of development and maintenance, not only of the mammary epithelial cell (MEC) population, but also of the mammary vasculature that sustains synthetic activity. Mammary biopsies were obtained from both mammary glands of 3 PP and 6 MP (>or=2 parity) dairy goats at parturition (d 1), d 10, 60, and 180 of lactation. Gene transcription relating to MEC turnover and vascular function was quantified by real-time reverse transcription-PCR, mammary morphology was characterized (quantitative histology), and cell turnover was determined (terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Ki-67). Primiparous glands showed higher expression for the genes involved in angiogenesis; namely, vascular endothelial growth factor receptor 2, and angiopoietin 1 and 2 and their receptor, a few days after parturition (d 10). Primiparous glands also had higher rates of MEC proliferation in early lactation. It therefore appears that initiation of lactation is associated with development and growth of the mammary gland into early lactation, which continues for a longer period in PP compared with MP glands. In addition, MEC survival was found to be higher in PP glands throughout lactation, and MEC in PP glands underwent more extensive differentiation. This could explain the reported flatter lactation curve and higher lactation persistency in PP glands. Although some of the genes included in this study were differentially expressed in PP and MP glands during the course of lactation, it was not possible to identify any specific genomic factor(s) that could account for

  13. Mammary field cancerization: molecular evidence and clinical importance.

    Science.gov (United States)

    Heaphy, Christopher M; Griffith, Jeffrey K; Bisoffi, Marco

    2009-11-01

    The term "field cancerization" originally denoted the presence of histologically abnormal tissue/cells surrounding primary tumors of the head and neck. Similar concepts with different and continuously changing definitions have been used for other types of tumors including breast adenocarcinoma, where field cancerization presently denotes the occurrence of molecular alterations in histologically normal tissues surrounding areas of overt cancer. Human mammary tissue morphology lends itself to the proposed concepts of field cancerization, which may include the gradual accumulation of genetic and other aberrations in stationary epithelial cells with intact morphology, or the spread of histologically normal yet genetically aberrant epithelial cells within mammary tissue. In this report, we review published molecular genetic, epigenetic, and gene expressional data in support of field cancerization in human mammary tissues. We then discuss the clinical implications of mammary field cancerization, including its source for potential biomarkers with diagnostic/prognostic potential, and its relationship to surgical margins and disease recurrence. We conclude with a future outlook on further research on mammary field cancerization addressing experimental methods, as well as the development of possible models and integrated approaches to gain a better understanding of the underlying mechanisms with the ultimate goal of developing clinical applications.

  14. Internal mammary sentinel lymph node biopsy: abandon or persist?

    Directory of Open Access Journals (Sweden)

    Qiu PF

    2016-06-01

    Full Text Available Peng-Fei Qiu, Yan-Bing Liu, Yong-Sheng Wang Breast Cancer Center, Shandong Cancer Hospital and Institute, Jinan, Shandong, People’s Republic of China Abstract: Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB concept, there has been little change in surgical practice patterns due to the low visualization rate of internal mammary sentinel lymph nodes with the traditional injection technique. Meanwhile, as internal mammary lymph nodes (IMLN metastases are mostly found concomitantly with axillary lymph nodes (ALN metastases, previous IM-SLNB clinical trials fail to evaluate the status of IMLN in patients who are really in need (only in clinically ALN negative patients. Our modified injection technique (periareolar intraparenchymal, high volume, and ultrasonographic guidance significantly improved the visualization rate of internal mammary sentinel lymph nodes, making the routine IM-SLNB possible in daily practice. IM-SLNB could provide individual minimally invasive staging, prognosis, and decision-making for breast cancer patients, especially for patients with clinically positive ALN. Moreover, IMLN radiotherapy should be tailored and balanced between the potential benefit and toxicity, and IM-SLNB-guided IMLN radiotherapy could achieve this goal. In the era of effective adjuvant therapy, within the changing treatment approach – more systemic therapy, less loco-regional therapy – clinicians should deliberate the application of regional IMLN therapy. Keywords: breast cancer, internal mammary lymph node, axillary lymph node, sentinel lymph node biopsy 

  15. File list: Unc.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: DNS.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: ALL.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: ALL.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: Oth.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: Pol.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Unc.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: DNS.Brs.20.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. File list: Oth.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: ALL.Brs.20.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Unc.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: Oth.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Oth.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Pol.Brs.10.AllAg.Mammary_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Brs.10.AllAg.Mammary_cells mm9 RNA polymerase Breast Mammary cells SRX187510,SR...X852566,SRX187515,SRX852567 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.10.AllAg.Mammary_cells.bed ...

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  10. File list: DNS.Brs.05.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Brs.05.AllAg.Mammary_epithelial_cells mm9 DNase-seq Breast Mammary epithelial c...ells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Brs.05.AllAg.Mammary_epithelial_cells.bed ...

  11. File list: His.Brs.10.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: His.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: Pol.Brs.50.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Brs.50.AllAg.Mammary_epithelial_cells mm9 RNA polymerase Breast Mammary epithel...ial cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.50.AllAg.Mammary_epithelial_cells.bed ...

  14. File list: His.Brs.20.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.20.AllAg.Mammary_epithelial_cells mm9 Histone Breast Mammary epithelial cel...ls SRX031075,SRX403485,SRX396749,SRX403486,SRX031213 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.20.AllAg.Mammary_epithelial_cells.bed ...

  15. File list: Pol.Brs.10.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Brs.10.AllAg.Mammary_epithelial_cells mm9 RNA polymerase Breast Mammary epithel...ial cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.10.AllAg.Mammary_epithelial_cells.bed ...

  16. File list: DNS.Brs.20.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: His.Brs.05.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: Oth.Brs.20.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.20.AllAg.Mammary_epithelial_cells mm9 TFs and others Breast Mammary epithel...ial cells SRX424872,SRX330636,SRX330635 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.20.AllAg.Mammary_epithelial_cells.bed ...

  19. File list: Oth.Brs.10.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.10.AllAg.Mammary_epithelial_cells mm9 TFs and others Breast Mammary epithel...ial cells SRX424872,SRX330636,SRX330635 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.10.AllAg.Mammary_epithelial_cells.bed ...

  20. File list: DNS.Brs.10.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  2. File list: Unc.Brs.05.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  3. File list: ALL.Brs.50.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.50.AllAg.Mammary_epithelial_cells mm9 All antigens Breast Mammary epithelia...SRX396750,SRX031066,SRX031214 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.50.AllAg.Mammary_epithelial_cells.bed ...

  4. File list: ALL.Brs.05.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

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  5. File list: Pol.Brs.20.AllAg.Mammary_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Brs.20.AllAg.Mammary_cells mm9 RNA polymerase Breast Mammary cells SRX852566,SR...X852567,SRX187510,SRX187515 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.20.AllAg.Mammary_cells.bed ...

  6. File list: Oth.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

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  7. File list: InP.Brs.20.AllAg.Mammary_cells [Chip-atlas[Archive

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    Full Text Available InP.Brs.20.AllAg.Mammary_cells mm9 Input control Breast Mammary cells SRX403481,SRX...187517,SRX187512,SRX403484 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.20.AllAg.Mammary_cells.bed ...

  8. File list: Pol.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

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  9. File list: ALL.Brs.20.AllAg.Mammary_cells [Chip-atlas[Archive

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  10. File list: ALL.Brs.10.AllAg.Mammary_cells [Chip-atlas[Archive

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  11. File list: InP.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

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    Full Text Available InP.Brs.50.AllAg.Mammary_cells mm9 Input control Breast Mammary cells SRX403481,SRX...187512,SRX187517,SRX403484 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.50.AllAg.Mammary_cells.bed ...

  12. File list: InP.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

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  13. File list: ALL.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

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  14. File list: ALL.Brs.20.AllAg.Mammary_tumor [Chip-atlas[Archive

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  15. File list: Oth.Brs.10.AllAg.Mammary_cells [Chip-atlas[Archive

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    Full Text Available Oth.Brs.10.AllAg.Mammary_cells mm9 TFs and others Breast Mammary cells SRX187508,SR...X187509,SRX187514,SRX403482,SRX403483,SRX852562,SRX852565,SRX187513,SRX852563,SRX852564 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.10.AllAg.Mammary_cells.bed ...

  16. File list: His.Brs.20.AllAg.Mammary_cells [Chip-atlas[Archive

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    Full Text Available His.Brs.20.AllAg.Mammary_cells mm9 Histone Breast Mammary cells SRX187511,SRX187516...,SRX403480,SRX403479 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.20.AllAg.Mammary_cells.bed ...

  17. File list: Oth.Brs.20.AllAg.Mammary_cells [Chip-atlas[Archive

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  18. File list: Pol.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

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    Full Text Available Pol.Brs.50.AllAg.Mammary_glands mm9 RNA polymerase Breast Mammary glands SRX1078976...,SRX1184165,SRX1078977,SRX1078989,SRX1078990 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.50.AllAg.Mammary_glands.bed ...

  19. File list: His.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.50.AllAg.Mammary_cells mm9 Histone Breast Mammary cells SRX187511,SRX187516...,SRX403479,SRX403480 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.50.AllAg.Mammary_cells.bed ...

  20. File list: His.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.05.AllAg.Mammary_cells mm9 Histone Breast Mammary cells SRX187511,SRX187516...,SRX403480,SRX403479 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.05.AllAg.Mammary_cells.bed ...

  1. File list: Unc.Brs.10.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.10.AllAg.Mammary_epithelial_cells mm9 Unclassified Breast Mammary epithelia...l cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.10.AllAg.Mammary_epithelial_cells.bed ...

  2. File list: Unc.Brs.20.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.20.AllAg.Mammary_epithelial_cells mm9 Unclassified Breast Mammary epithelia...l cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.20.AllAg.Mammary_epithelial_cells.bed ...

  3. File list: Pol.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Brs.50.AllAg.Mammary_stem_cells mm9 RNA polymerase Breast Mammary stem cells ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.50.AllAg.Mammary_stem_cells.bed ...

  4. File list: Unc.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.10.AllAg.Mammary_stem_cells mm9 Unclassified Breast Mammary stem cells http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.10.AllAg.Mammary_stem_cells.bed ...

  5. File list: His.Brs.20.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.20.AllAg.Mammary_stem_cells mm9 Histone Breast Mammary stem cells SRX213393...,SRX213410,SRX185869,SRX185809,SRX213404,SRX213407 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.20.AllAg.Mammary_stem_cells.bed ...

  6. File list: His.Brs.10.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.10.AllAg.Mammary_stem_cells mm9 Histone Breast Mammary stem cells SRX213393...,SRX213410,SRX213404,SRX213407,SRX185869,SRX185809 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.10.AllAg.Mammary_stem_cells.bed ...

  7. File list: His.Brs.50.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: DNS.Brs.05.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Brs.05.AllAg.Mammary_stem_cells mm9 DNase-seq Breast Mammary stem cells SRX1886...40,SRX191028 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Brs.05.AllAg.Mammary_stem_cells.bed ...

  9. File list: ALL.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.50.AllAg.Mammary_cells mm9 All antigens Breast Mammary cells SRX187508,SRX1...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.50.AllAg.Mammary_cells.bed ...

  10. File list: His.Brs.10.AllAg.Mammary_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.10.AllAg.Mammary_cells mm9 Histone Breast Mammary cells SRX187511,SRX187516...,SRX403480,SRX403479 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.10.AllAg.Mammary_cells.bed ...

  11. File list: His.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.05.AllAg.Mammary_glands mm9 Histone Breast Mammary glands ERX200400,SRX2134...,ERX200419,ERX200401,ERX200405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.05.AllAg.Mammary_glands.bed ...

  12. File list: Oth.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.05.AllAg.Mammary_glands mm9 TFs and others Breast Mammary glands ERX200430,...200399 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.05.AllAg.Mammary_glands.bed ...

  13. File list: Unc.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.50.AllAg.Mammary_glands mm9 Unclassified Breast Mammary glands SRX216177 ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.50.AllAg.Mammary_glands.bed ...

  14. File list: Pol.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Brs.10.AllAg.Mammary_glands mm9 RNA polymerase Breast Mammary glands SRX1184165...,SRX1078977,SRX1078976,SRX1078989,SRX1078990 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.10.AllAg.Mammary_glands.bed ...

  15. File list: Unc.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.20.AllAg.Mammary_glands mm9 Unclassified Breast Mammary glands SRX216177 ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.20.AllAg.Mammary_glands.bed ...

  16. File list: InP.Brs.10.AllAg.Mammary_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.10.AllAg.Mammary_cells mm9 Input control Breast Mammary cells SRX403481,SRX...187517,SRX187512,SRX403484 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.10.AllAg.Mammary_cells.bed ...

  17. File list: InP.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.05.AllAg.Mammary_glands mm9 Input control Breast Mammary glands SRX213417,S...00420,ERX200416,ERX200438,SRX1078980,ERX200398,ERX200402 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.05.AllAg.Mammary_glands.bed ...

  18. File list: Unc.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.10.AllAg.Mammary_glands mm9 Unclassified Breast Mammary glands SRX216177 ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.10.AllAg.Mammary_glands.bed ...

  19. File list: InP.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.20.AllAg.Mammary_glands mm9 Input control Breast Mammary glands SRX213420,S...0406,ERX200402,SRX1078980,SRX396747,SRX396745,SRX1078982 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.20.AllAg.Mammary_glands.bed ...

  20. File list: ALL.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.20.AllAg.Mammary_glands mm9 All antigens Breast Mammary glands SRX209678,SR...31209,SRX031208,SRX031071,SRX216177,SRX1078980,SRX396747,SRX396745,SRX1078982 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.20.AllAg.Mammary_glands.bed ...

  1. File list: InP.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.10.AllAg.Mammary_glands mm9 Input control Breast Mammary glands SRX213411,E...200398,ERX200420,ERX200438,ERX200429,ERX200402,SRX396747 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Brs.10.AllAg.Mammary_glands.bed ...

  2. File list: Pol.Brs.05.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Brs.05.AllAg.Mammary_glands mm9 RNA polymerase Breast Mammary glands SRX1078977...,SRX1184165,SRX1078989,SRX1078976,SRX1078990 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.05.AllAg.Mammary_glands.bed ...

  3. File list: Oth.Brs.05.AllAg.Mammary_epithelial_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.05.AllAg.Mammary_epithelial_cells mm9 TFs and others Breast Mammary epithel...ial cells SRX424872,SRX330635,SRX330636 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.05.AllAg.Mammary_epithelial_cells.bed ...

  4. File list: ALL.Brs.10.AllAg.Mammary_tumor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.10.AllAg.Mammary_tumor mm9 All antigens Breast Mammary tumor SRX700365,SRX7...00366 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.10.AllAg.Mammary_tumor.bed ...

  5. File list: Pol.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Brs.50.AllAg.Mammary_cells mm9 RNA polymerase Breast Mammary cells SRX852566,SR...X187510,SRX852567,SRX187515 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.50.AllAg.Mammary_cells.bed ...

  6. File list: ALL.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.10.AllAg.Mammary_glands mm9 All antigens Breast Mammary glands SRX213411,SR...X200417,ERX200426,ERX200435,SRX396747,ERX200437,ERX200399,ERX200405,ERX200401 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.10.AllAg.Mammary_glands.bed ...

  7. File list: Oth.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.10.AllAg.Mammary_glands mm9 TFs and others Breast Mammary glands SRX209678,...200399 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.10.AllAg.Mammary_glands.bed ...

  8. File list: ALL.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.50.AllAg.Mammary_glands mm9 All antigens Breast Mammary glands SRX396744,SR...31072,SRX031071,SRX031211,SRX216177,SRX1078980,SRX396747,SRX396745,SRX1078982 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.50.AllAg.Mammary_glands.bed ...

  9. File list: His.Brs.50.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.50.AllAg.Mammary_glands mm9 Histone Breast Mammary glands SRX396744,SRX1184...,SRX031072,SRX031071,SRX031211 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.50.AllAg.Mammary_glands.bed ...

  10. File list: Pol.Brs.20.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Brs.20.AllAg.Mammary_glands mm9 RNA polymerase Breast Mammary glands SRX1184165...,SRX1078976,SRX1078977,SRX1078989,SRX1078990 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Brs.20.AllAg.Mammary_glands.bed ...

  11. File list: ALL.Brs.05.AllAg.Mammary_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.05.AllAg.Mammary_cells mm9 All antigens Breast Mammary cells SRX187511,SRX1...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.05.AllAg.Mammary_cells.bed ...

  12. File list: His.Brs.10.AllAg.Mammary_glands [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.10.AllAg.Mammary_glands mm9 Histone Breast Mammary glands SRX396744,SRX1184...,ERX200437,ERX200405,ERX200401 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Brs.10.AllAg.Mammary_glands.bed ...

  13. File list: Oth.Brs.50.AllAg.Mammary_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.50.AllAg.Mammary_cells mm9 TFs and others Breast Mammary cells SRX187508,SR...X187509,SRX187514,SRX403482,SRX852562,SRX187513,SRX403483,SRX852565,SRX852563,SRX852564 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Brs.50.AllAg.Mammary_cells.bed ...

  14. File list: Unc.Brs.20.AllAg.Mammary_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.20.AllAg.Mammary_stem_cells mm9 Unclassified Breast Mammary stem cells http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Brs.20.AllAg.Mammary_stem_cells.bed ...

  15. File list: ALL.Brs.05.AllAg.Mammary_tumor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.05.AllAg.Mammary_tumor mm9 All antigens Breast Mammary tumor SRX700365,SRX7...00366 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.05.AllAg.Mammary_tumor.bed ...

  16. File list: ALL.Brs.50.AllAg.Mammary_tumor [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.50.AllAg.Mammary_tumor mm9 All antigens Breast Mammary tumor SRX700365,SRX7...00366 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Brs.50.AllAg.Mammary_tumor.bed ...

  17. Carcinoma Basocelular

    Directory of Open Access Journals (Sweden)

    Inês Alencar de Castro

    2008-03-01

    Full Text Available Vemos na região frontal de um paciente masculino, fototipo II de Fitzpatrick, lesão ulcerada com bordas papulosas róseas e peroladas, correspondendo a Carcinoma Basocelular. É lesão maligna originária das células não- queratinizadas da camada basal da epiderme, sendo a forma mais comum de câncer em humanos. Estima-se em torno de 100.000 casos/ano no Brasil. Ocorre predominantemente em pele exposta de indivíduos com pouca capacidade de se bronzear. Pode se tornar invasivo, mas raramente metastatiza.

  18. Carcinoma basocelular

    OpenAIRE

    Nunes, Daniel Holthausen.

    2013-01-01

    Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Médicas, Florianópolis, 2013. Introdução: O carcinoma basocelular (CBC) é o tumor maligno de pele mais comum em humanos. Atualmente existem inúmeras terapias para tratar o CBC, entretanto não se sabe se a inflamação peritumoral influencia na decisão cirúrgica, nem que fatores adicionais influenciam na qualidade de vida (QV) de seus portadores. Objetivos: 1) Aval...

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

    Science.gov (United States)

    Shafiee, Radmehr; Javanbakht, Javad; Atyabi, Nahid; Bahrami, Alimohammad; Kheradmand, Danial; Safaei, Reyhaneh; Khadivar, Farshid; Hosseini, Ehsan

    2013-08-13

    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. 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. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2047361423103295.

  20. Gene expression analysis on small numbers of invasive cells collected by chemotaxis from primary mammary tumors of the mouse

    Directory of Open Access Journals (Sweden)

    Segall Jeffrey E

    2003-08-01

    Full Text Available Abstract Background cDNA microarrays have the potential to identify the genes involved in invasion and metastasis. However, when used with whole tumor tissue, the results average the expression patterns of different cell types. We have combined chemotaxis-based cell collection of the invasive subpopulation of cells within the primary tumor with array-based gene expression analysis to identify the genes necessary for the process of carcinoma cell invasion. Results Invasive cells were collected from live primary tumors using microneedles containing chemotactic growth factors to mimic chemotactic signals thought to be present in the primary tumor. When used with mammary tumors of rats and mice, carcinoma cells and macrophages constitute the invasive cell population. Microbeads conjugated with monoclonal anti-CD11b (Mac-1α antibodies were used to separate macrophages from carcinoma cells. We utilized PCR-based cDNA amplification from small number of cells and compared it to the quality and complexity of conventionally generated cDNA to determine if amplified cDNA could be used with fidelity for array analysis of this cell population. These techniques showed a very high level of correlation indicating that the PCR based amplification technique yields a cDNA population that resembles, with high fidelity, the original template population present in the small number of cells used to prepare the cDNA for use with the chip. Conclusions The specific collection of invasive cells from a primary tumor and the analysis of gene expression in these cells are is now possible. By further comparing the gene expression patterns of cells collected by invasion into microneedles with that of carcinoma cells obtained from the whole primary tumor, the blood, and whole metastatic tumors, genes that contribute to the invasive process in carcinoma cells may be identified.

  1. FOXC1 is enriched in the mammary luminal progenitor population, but is not necessary for mouse mammary ductal morphogenesis.

    Science.gov (United States)

    Sizemore, Gina M; Sizemore, Steven T; Pal, Bhupinder; Booth, Christine N; Seachrist, Darcie D; Abdul-Karim, Fadi W; Kume, Tsutomu; Keri, Ruth A

    2013-07-01

    Expression of FOXC1, a forkhead box transcription factor, correlates with the human basal-like breast cancer (BLBC) subtype, and functional analyses have revealed its importance for in vitro invasiveness of BLBC cells. Women diagnosed with this breast tumor subtype have a poorer outcome because of the lack of targeted therapies; thus, continued investigation of factors driving these tumors is critical to uncover novel therapeutic targets. Several processes that dictate normal mammary morphogenesis parallel cancer progression, and enforced expression of FOXC1 can induce a progenitor state in more-differentiated mammary epithelial cells. Consequently, evaluating how FOXC1 functions in the normal gland is critical to further understand BLBC biology. Although FOXC1 is well known to control normal development of a number of tissues, its role in the mammary gland has not yet been investigated. Herein, we describe FOXC1 expression patterning in the normal breast, where it is localized to the basal/myoepithelium, suggesting that FOXC1 would be required for normal development. However, mammary glands lacking Foxc1 have no overt defect in ductal outgrowth, alveologenesis, or lineage specification. Of significant interest, we found that expression of FOXC1 is enriched in the normal luminal progenitor population, which is the postulated cell of origin of BLBC. These results indicate that FOXC1 is unnecessary for mammary morphogenesis and that its role in BLBC likely involves processes that are unrelated to cell lineage specification.

  2. Mammary Gland Reprogramming: Metalloproteinases Couple Form with Function

    Science.gov (United States)

    Khokha, Rama; Werb, Zena

    2011-01-01

    The adult mammary structure provides for the rapid growth, development, and immunological protection of the live-born young of mammals through its production of milk. The dynamic remodeling of the branched epithelial structure of the mammary gland in response to physiological stimuli that allow its programmed branching morphogenesis at puberty, cyclical turnover during the reproductive cycle, differentiation into a secretory organ at parturition, postlactational involution, and ultimately, regression with age is critical for these processes. Extracellular metalloproteinases are essential for the remodeling programs that operate in the tissue microenvironment at the interface of the epithelium and the stroma, coupling form with function. Deregulated proteolytic activity drives the transition of a physiological mammary microenvironment into a tumor microenvironment, facilitating malignant transformation. PMID:21106646

  3. Energetics and mammary carcinogenesis: effects of moderate-intensity running and energy intake on cellular processes and molecular mechanisms in rats.

    Science.gov (United States)

    Zhu, Zongjian; Jiang, Weiqin; McGinley, John N; Thompson, Henry J

    2009-03-01

    The objective of this experiment was to determine the effects on mammary carcinogenesis of similar limitations in energy availability either by energy expenditure due to moderate-intensity running (physical activity, PA) or by regulating dietary energy (RE) intake relative to a sedentary control (SC) group that ate ad libitum. A total of 90 female Sprague-Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter were randomized to either SC, a PA group given free access to a motorized running wheel, or a RE group whose food intake limited growth to the rate observed in PA. Compared with SC, mammary carcinogenesis was inhibited by RE or PA. Cancer incidence, 92.6%, 77.8%, and 66.7% (P = 0.06), and cancer multiplicity, 3.44, 2.11, and 1.62 cancers/rat (P = 0.006), in SC, RE, and PA, respectively, were reduced to a similar extent by RE and PA. Histological and Western blot analyses of mammary carcinomas provided evidence that RE and PA induced apoptosis via the mitochondrial pathway, that cell cycle progression was suppressed at the G(1)/S transition, and that intratumoral blood vessel density was reduced, although it remains to be determined whether PA and RE exert these effects via the same mechanisms.

  4. CD10 positive recurrent undifferentiated mammary sarcoma in a young female: a rare case report with brief review of literature

    Directory of Open Access Journals (Sweden)

    Kachnar Varma

    2015-06-01

    Full Text Available Undifferentiated mammary sarcoma is extremely rare and the diagnosis is made only after exclusion of metaplastic carcinomas and malignant phyllodes tumor. Mammary sarcomas mostly display specified entities like liposarcomas or angiosarcomas. A 18-year-old female presented in 2010 with a right breast lump for which lumpectomy was done and on histopathological examination benign phyllodes tumor was diagnosed. In 2011, there was a recurrence at site of excised margin and on fine needle aspiration (FNA the diagnosis of benign breast disease was made; a small biopsy was received for which diagnosis of myoepithelial lesion was given. Then, the whole mass was excised, but histopathological examination report could not be followed up. In 2013, she again presented with a mass arising from the previously excised margin; on FNA, it was diagnosed as malignant sarcomatous lesion. Microscopy showed spindle shaped cells in diffuse and fascicular pattern with plump ovoid nuclei; coarse chromatin and eosinophilic cytoplasm were seen. Few round to ovoid cells with eccentric nuclei and showing bi- or multi-nucleation were present. Large area of necrosis and hemorrhage was present, too. No breast glands were found. Later on, diagnosis was confirmed on immunohistochemical examination. The case was considered worth due to the young age of the patient and lack of differentiation of the lesion in any specific type of sarcoma and CD10 positivity.

  5. Mammary mechanisms for lactoferrin: interactions with IGFBP-3.

    Directory of Open Access Journals (Sweden)

    Baumrucker C.R.

    2000-01-01

    Full Text Available Lactoferrin (Lf is an iron-binding protein found in high concentrations in mammary secretions but synthesized by many tissues. Bovine mammary tissue secretes microg/ml mass of Lf in milk, but during involution and prepartum periods, 20-80 mg per ml concentrations may be observed. While a number of functions have been ascribed to lactoterrin, only the antimicrobial and lymphocyte interactions have compelling experimental evidence of support. We report a new finding that lactoferrin binds to insulin-like growth factor binding protein-3 (IGFBP-3 and not to other mammary secreted IGFBPs (IGFBP-2, -4. and -5. Furthermore, bovine Lf(bLf is found associated with membranes of mammary cells. We demonstrate that bovine Lf competes with IGF for binding to IGFBP-3 with ED50 competition of 3 microg per ml and displacement of 1 mg per ml to monomeric bLf. The tetrameric form that is favored by high concentrations of Lf and calcium, does not appear to bind IGFBP-3. Both IGFBP-3 and Lf have nuclear localization sequences that are reported to he key components of nuclear localization of proteins. We demonstrate that extracellular IGFBP-3 binds to membrane Lf and that Lf is the key to the entry of IGFBP-3 to mammary cellular nucleus. Additionally, we have shown that the internalization of Lf requires the presence of retinoids that also induces both IGFBP-3 and Lf synthesis in primary cultures of bovine mammary epithelial cells. We hypothesize a new role for Lf in the regulation and integration into the IGF System.

  6. The mammary gland in domestic ruminants: a systems biology perspective.

    Science.gov (United States)

    Ferreira, Ana M; Bislev, Stine L; Bendixen, Emøke; Almeida, André M

    2013-12-06

    Milk and dairy products are central elements in the human diet. It is estimated that 108kg of milk per year are consumed per person worldwide. Therefore, dairy production represents a relevant fraction of the economies of many countries, being cattle, sheep, goat, water buffalo, and other ruminants the main species used worldwide. An adequate management of dairy farming cannot be achieved without the knowledge on the biological mechanisms behind lactation in ruminants. Thus, understanding the morphology, development and regulation of the mammary gland in health, disease and production is crucial. Presently, innovative and high-throughput technologies such as genomics, transcriptomics, proteomics and metabolomics allow a much broader and detailed knowledge on such issues. Additionally, the application of a systems biology approach to animal science is vastly growing, as new advances in one field of specialization or animal species lead to new lines of research in other areas or/and are expanded to other species. This article addresses how modern research approaches may help us understand long-known issues in mammary development, lactation biology and dairy production. Dairy production depends upon the knowledge of the morphology and regulation of the mammary gland and lactation. High-throughput technologies allow a much broader and detailed knowledge on the biology of the mammary gland. This paper reviews the major contributions that genomics, transcriptomics, metabolomics and proteomics approaches have provided to understand the regulation of the mammary gland in health, disease and production. In the context of mammary gland "omics"-based research, the integration of results using a Systems Biology Approach is of key importance. © 2013.

  7. Metastatic nonpalpable invasive lobular breast carcinoma presenting as rectal stenosis: a case report.

    Science.gov (United States)

    Osaku, Tadatoshi; Ogata, Hideaki; Magoshi, Shunsuke; Kubota, Yorichika; Saito, Fumi; Kanazawa, Shinsaku; Kaneko, Hironori

    2015-04-24

    Invasive lobular carcinomas have an increased propensity for distant metastases, particularly to the peritoneum, ovaries, and uterus. In contrast, distant metastases of nonpalpable lobular carcinomas are extremely rare, and the causes of underlying symptoms of primary carcinomas remain unclear. We report a case of an asymptomatic invasive lobular carcinoma with a primary mammary lesion in a patient with rectal stenosis. A 69-year-old Japanese woman presented to our hospital for treatment of constipation. Although rectal stenosis was confirmed, thorough testing of her lower digestive tract did not identify its cause. Thus, an exploratory laparotomy and tissue biopsy was performed, and the presence of an invasive lobular carcinoma was confirmed. Subsequent breast examinations showed that the invasive lobular carcinoma that led to the rectal stenosis was a metastatic lesion from a primary lesion of the breast duct. As the present breast lobular carcinoma was asymptomatic and nonpalpable, we did not initially consider metastatic breast cancer as a cause of her symptoms, and the final diagnosis was delayed. Peritoneal metastasis from nonpalpable invasive lobular carcinomas is very rare. However, breast cancer metastasis should be considered when carcinomatous peritonitis is present in a patient with an unknown primary cancer.

  8. Vulnerability of Normal Human Mammary Epithelial Cells to Oncogenic Transformation

    Science.gov (United States)

    2012-04-01

    escape senescence and acquire genomic changes. Nature 2001;409:633–7. 10. Olsen CL, Gardie B, Yaswen P, Stampfer MR. Raf-1- induced growth arrest in...p16INK4a. Cell 88:593–602. 10. Olsen CL, Gardie B, Yaswen P, Stampfer MR (2002) Raf-1-induced growth arrest in human mammary epithelial cells is p16...Cycle 3, 244–246. Olsen CL, Gardie B, Yaswen P, Stampfer MR (2002) Raf-1-induced growth arrest in human mammary epithelial cells is p16-independent and

  9. Establishment and characterization of eight feline mammary adenocarcinoma cell lines.

    Science.gov (United States)

    Uyama, Rina; Hong, Sung-Hyeok; Nakagawa, Takayuki; Yazawa, Mitsuhiro; Kadosawa, Tsuyoshi; Mochizuki, Manabu; Tsujimoto, Hajime; Nishimura, Ryohei; Sasaki, Nobuo

    2005-12-01

    Eight new feline mammary adenocarcinoma cell lines derived from either primary or metastatic lesions were established. The morphology of all the cell lines was epithelioid and round to spindle in shape, with cell growth occurring in a monolayer fashion. On immunohistochemistry, these cells reacted with anti-keratin and anti-vimentin antisera. The doubling time of these cells was between 19 and 54 hr. Tumor masses were developed in nude mice by subcutaneous inoculation of the cells that were histologically identical to their original mammary tumor lesions. Telomerase activities measured using the telomeric repeat amplification protocol assay revealed high telemetric activity in all of the cells.

  10. NMR characteristics of rat mammary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Osbakken, M.; Kreider, J.; Taczanowsky, P.

    1984-01-01

    12 rats were injected intradermally with 13762A rat mammary adenocarcinoma (1 x 10/sup 6/ cells). 3 rats died before completion of the study and 2 rat had tumor regression; the first 3 were excluded from data analysis. NMR imaging with a 1.5K gauss resistive magnet at 2, 3, 4, and 5 weeks after injection demonstrated increasing tumor mass. Saturation recovery (SR), inversion recovery (IR), and spin echo (SE) pulse sequence images and T/sub 1/ calculation were done for tumor characterization. (Tumor size was too small to identify at 2 weeks.) 3 rats were sacrificed after the last 3 imaging periods for histological studies, done to distinguish solid tumor mass from necrosis. Planimetry of tumor areas showed that as tumors grew in size, the ratio of necrotic area to area of solid tumor increased (week 3 = .3 +- .11; week 4 = .45 +- .07; week 5 = .51 +- 05); simultaneous calculated T/sub 1/ values also increased (week 3 = .35 +- .15; week 4 = .45 +- .06; week 5 = .42 +- 03). Qualitative NMR image T/sub 1/ values also increased as evidenced by progression of SR and IR tumor image intensity from very bright compared to the rest of the body at week 3 to less intense than other structures at week 5. These findings indicate that change in T/sub 1/ may be secondary to the pathophysiological change in the tumor (the increasing in necrosis, associated with increased free water). Thus, the range of T/sub 1/ values obtained in tumors in this study (and in previous studies) may be due to change in tumor physiology and anatomy. Careful correlation of histological with NMR data may allow ultimate use of NMR relaxation characteristics for determination of the physiological state of tumors.

  11. Radiogenic neoplasia in thyroid and mammary clonogens

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. A Review of the Use of Fine-Needle Aspiration Biopsy of Mammary Tumors for Diagnosis and Research.

    Science.gov (United States)

    Tani, Edneia; Fuentes-Martinez, Nelson; Skoog, Lambert

    2017-01-01

    The article "Aspiration Biopsy of Mammary Tumors in Diagnosis and Research - A Critical Review of 2,200 Cases" by Zajicek et al. [Acta Cytol 1967;11:169-175] is composed of two separate parts as can be seen from the title. Both are, however, of great historical interest. The first describes the early days of fine-needle aspiration cytology diagnosis of breast lesions in particular carcinomas. The results are still impressive with a diagnostic accuracy close to 90%. The second deals with the effect of negative pressure on cell viability during the aspiration procedure. These studies were aimed at evaluating the usefulness of aspirated tumor cells to analyze the effects of therapy and the origin of tumor cells. © 2017 S. Karger AG, Basel.

  13. Technical note: Measurement of mammary plasma flow in sows by downstream dilution of mammary vein infused para-aminohippuric acid

    DEFF Research Database (Denmark)

    Larsen, Uffe Krogh; Storm, Adam Christian; Theil, Peter Kappel

    2016-01-01

    catheter was surgically implanted in the femoral artery, and another 2 were inserted in the right cranial mammary vein of 8 second- and third-parity sows on d 76 ± 2 SEM of gestation. On the 3rd and 17th days in milk, arterial and venous blood samples were drawn in hourly intervals from 0.5 h before until...... 6.5 h after feeding. The MPF in the right cranial mammary vein was measured by downstream dilution of infused pAH (3.0 mmol/h). Total MPF-pAH was calculated assuming that the measured flow constituted the flow from 5 out of 14 suckled glands on the basis of the anatomical structure of the mammary...

  14. Is mammary not otherwise specified-type sarcoma with CD10 expression a distinct entity? A rare case report with immunohistochemical and ultrastructural study

    Directory of Open Access Journals (Sweden)

    Yang Guang-Zhi

    2013-01-01

    Full Text Available Abstract Mammary sarcoma is extremely rare and the diagnosis is established only after metaplastic carcinomas and malignant phyllodes tumours are excluded. A rare case of not otherwise specified-type sarcoma with CD10 expression in the left breast in a 45-year-old female was presented. It was a high-grade tumour composed of spindle cells histologically. The immunohistochemical results showed that CD10, vimentin and EGFR were positive diffusely and SMA presented focally, whereas epithelial markers and other myoepithelial or myogenic markers were all negative. The electron microscope investigation demonstrated fibroblast-like features. The exact entity of the tumour remains to be studied because it resembles undifferentiated sarcoma or sarcomatoid metaplastic carcinoma to some degree, as well as high-grade malignant phyllodes tumour in particular. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9019879588725702

  15. Does the correlation between EBNA-1 and p63 expression in breast carcinomas provide a clue to tumorigenesis in Epstein-Barr virus-related breast malignancies?

    Directory of Open Access Journals (Sweden)

    Ribeiro-Silva A.

    2004-01-01

    Full Text Available Several investigators have identified Epstein-Barr virus (EBV particles in breast carcinomas, a fact that supports a role for EBV in mammary tumorigenesis. The possible mechanism involved in this process is not clear. The present study was carried out in an attempt to determine whether there is a relationship between latent infection with EBV and p53 and p63 expression in breast carcinomas. Immunohistochemistry developed with 3.3-diaminobenzidine tetrahydrochloride was performed in 85 formalin-fixed paraffin-embedded breast carcinomas using anti-EBV EBNA-1, anti-p63, anti-p53, anti-estrogen receptor (ER and anti-progesterone receptor (PR antibodies. The cases were selected to represent each of the various histologic types: intraductal carcinoma (N = 12, grade I invasive ductal carcinoma (N = 15, grade II invasive ductal carcinoma (N = 15, grade III invasive ductal carcinoma (N = 15, tubular carcinoma (N = 8, lobular carcinoma (N = 10, and medullary carcinoma (N = 10. The ductal breast carcinomas were graded I, II and III based on the Scarff-Bloom and Richardson grading system modified by Elston and Ellis. One slide containing at least 1000 neoplastic cells was examined in each case. ER, PR, p63, p53 and EBNA-1 were positive in 60, 40, 11.8, 21.2 and 37.6% of carcinomas, respectively. There was a correlation between EBNA-1 and p63 expression (P < 0.001, but not between EBNA-1 and p53 (P = 0.10. These data suggest a possible role for p63 in the mammary tumorigenesis associated with Epstein-Barr virus infection.

  16. Lobular carcinoma in situ and invasive lobular breast cancer are characterized by enhanced expression of transcription factor AP-2β.

    Science.gov (United States)

    Raap, Mieke; Gronewold, Malte; Christgen, Henriette; Glage, Silke; Bentires-Alj, Mohammad; Koren, Shany; Derksen, Patrick W; Boelens, Mirjam; Jonkers, Jos; Lehmann, Ulrich; Feuerhake, Friedrich; Kuehnle, Elna; Gluz, Oleg; Kates, Ronald; Nitz, Ulrike; Harbeck, Nadia; Kreipe, Hans H; Christgen, Matthias

    2018-01-01

    Transcription factor AP-2β (TFAP2B) regulates embryonic organ development and is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene expression profiling has implicated AP-2β in breast cancer (BC). This study characterizes AP-2β expression in the mammary gland and in BC. AP-2β protein expression was assessed in the normal mammary gland epithelium, in various reactive, metaplastic and pre-invasive neoplastic lesions and in two clinical BC cohorts comprising >2000 patients. BCs from various genetically engineered mouse (GEM) models were also evaluated. Human BC cell lines served as functional models to study siRNA-mediated inhibition of AP-2β. The normal mammary gland epithelium showed scattered AP-2β-positive cells in the luminal cell layer. Various reactive and pre-invasive neoplastic lesions, including apocrine metaplasia, usual ductal hyperplasia and lobular carcinoma in situ (LCIS) showed enhanced AP-2β expression. Cases of ductal carcinoma in situ (DCIS) were more often AP-2β-negative (Pinvasive BC cohorts, AP-2β-positivity was associated with the lobular BC subtype (Plobular BC cell lines in vitro. In summary, AP-2β is a new mammary epithelial differentiation marker. Its expression is preferentially retained and enhanced in LCIS and invasive lobular BC and has prognostic implications. Our findings indicate that AP-2β controls tumor cell proliferation in this slow-growing BC subtype.

  17. Ghrelin is expressed in the pregnant mammary glands of dairy goats and promotes the cell proliferation of mammary epithelial cells.

    Science.gov (United States)

    Zhang, Wenlong; Zhang, Zelin; Chen, Jinxuan; Tong, Dewen

    2018-01-20

    Little is known about ghrelin's effects on cell proliferation in pregnant mammary epithelial cells (MECs) even though it is known 4 to be a mitogen for a variety of other cell types. The objectives of this study were to evaluate the expression and localization of ghrelin and its functional receptor, GHSR-1a, in the mammary glands of dairy goats during pregnancy and to investigate the direct role of ghrelin in cell proliferation of primary cultured MECs. Compared to the early stage (days 30) of pregnancy, the abundance of transcripts and protein of ghrelin and GHSR-1a were significantly greater in mid- and late-phases (between days 90 and days 120) of pregnancy (p < 0.05). Immunohistochemistry analysis showed that ghrelin and GHSR-1a were predominantly localized in the alveolar and ductal mammary epithelial cells at various stages of pregnancy. In our in vitro experiments, ghrelin induced a dose- and time- dependent promotory effect on cell proliferation of MECs. At the dose of 103 pg/mL treatment 24 h, ghrelin augmented the expression of proliferation-related peptides (PCNA and cyclin B1). Furthermore, ghrelin promoted the expression of prolactin (PRL) and GHSR-1a in cultured MECs. Additionally, the the stimulatory effects of ghrelin were blocked by D-Lys3-GHRP6, a selective antagonist of GHSR-1a. As the temporal changes in ghrelin and GHSR-1a expression in pregnant goat mammary glands coincided with the mammary growth and development during the pregnancy, activation of GHSR-1a signal transduction pathways by ghrelin may play a direct role in the regulation of mammary growth in dairy goats. Copyright © 2018. Published by Elsevier Inc.

  18. Clinical Significance of Internal Mammary Lymph Node Biopsy during Microsurgical Breast Reconstruction: Review of 264 Cases.

    Science.gov (United States)

    Wright, Eric J; Momeni, Arash; Kraneburg, Ursula M; Otake, Leo R; Echo, Anthony; Lee, Tim; Buchanan, Edward P; Lee, Gordon K

    2016-06-01

    Despite the knowledge of alternate lymphatic draining patterns of the breast, routine evaluation of the internal mammary lymph node basin is still not considered standard of care. The advent of microsurgical breast reconstruction using the internal mammary vessels as recipients, however, has allowed sampling of internal mammary lymph nodes with technical ease, thus revisiting their role in breast cancer management. In the present study, the authors reviewed their experience with this practice. A retrospective analysis of patients who underwent internal mammary lymph node biopsy at the time of autologous breast reconstruction using the internal mammary vessels between 2004 and 2012 was performed. Parameters of interest included patient age, timing of reconstruction (immediate versus delayed), disease stage, and pathologic findings of internal mammary lymph nodes. A total of 264 autologous breast reconstructions using the internal mammary vessels were performed in 204 patients with a median age of 44.5 years. The majority of reconstructions were immediate [n = 211 (79.9 percent)]. Seventy-two percent of patients had either stage I [72 patients (35.3 percent)] or stage II disease [75 patients (36.8 percent)]. Six patients were found to have internal mammary lymph node metastasis. Stage migration and alteration in adjuvant therapy occurred in all patients. Internal mammary lymph node sampling at the time of autologous breast reconstruction using the internal mammary system should become routine practice, as the morbidity associated with internal mammary lymph node harvest is low and the impact in cases of nodal involvement is quite substantial. Therapeutic, IV.

  19. The effect of zinc and phytoestrogen supplementation on the changes in mineral content of the femur of rats with chemically induced mammary carcinogenesis.

    Science.gov (United States)

    Skrajnowska, Dorota; Korczak, Barbara Bobrowska-; Tokarz, Andrzej; Kazimierczuk, Agata; Klepacz, Marta; Makowska, Justyna; Gadzinski, Blazej

    2015-10-01

    The aim of this study was to assess skeletal effects of zinc or zinc with phytoestrogen (resveratrol or genistein) supplementation in an animal model of rats with DMBA-induced mammary carcinogenesis. The changes in bone parameters such as the length and mass were examined, as well as the changes in concentrations of selected minerals: calcium, magnesium, zinc, iron and phosphorus. Moreover, the investigations focused on finding the differences between the levels of iron and zinc in other tissues: the liver, spleen and serum of the examined rats. Fifty-six female Sprague-Dawley rats, 40 days old, were divided into four groups, regardless of the diets: standard (77mg Zn kg/food), zinc (4.6mg/mL via gavage), zinc (4.6mg/mL) plus resveratrol (0.2mg/kgbw), and zinc (4.6mg/mL) plus genistein (0.2mg/kgbw) for a period from 40 days until 20 weeks of age. The study rats were also treated with 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) to induce mammary carcinogenesis. The applied diet and the advanced mammary cancer did not affect macrometric parameters of the rats' bones, but they strongly affected their mineral content. It was found that mammary cancer, irrespectively of the applied diet, significantly modified the iron level in the femur, liver, spleen and serum of the examined rats. In addition, zinc supplementation significantly lowered the levels of calcium, magnesium and phosphorus in the femur of rats with mammary cancer as compared with respective levels in the control group. So, it was found that additional supplementation with zinc, which is generally considered to be an antioxidant, with the co-existing mammary carcinoma, increased the unfavorable changes as concerns the stability of bone tissue. The appropriate combination of zinc and phytoestrogens (resveratrol or genistein) could help prevent or slow bone loss associated with a range of skeletal disorders in breast cancer. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. The male mammary gland: a target for the xenoestrogen bisphenol A.

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Inc. All rights reserved.