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Sample records for canine hematopoietic tumors

  1. Classification and grading of canine malignant mammary tumors

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    Abbas Tavasoly; Hannaneh Golshahi; Annahita Rezaie; Mohammad Farhadi

    2013-01-01

    Histological grading is a good parameter to stratify tumors according to their biological aggressiveness. The Elston and Ellis grading method in humans, invasive ductal breast carcinomas and other invasive tumors are routinely used. The aims of this study were classification of mammary gland tumors and also application of a human grading method in canine mammary carcinoma. The samples included 37 tumors of mammary glands. Mammary tumors were carcinomas (n = 32) and sarcomas (n = 5). The carci...

  2. Frequent alteration of the tumor suppressor gene APC in sporadic canine colorectal tumors.

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    Lydia Youmans

    Full Text Available Sporadic canine colorectal cancers (CRCs should make excellent models for studying the corresponding human cancers. To molecularly characterize canine CRC, we investigated exonic sequence mutations of adenomatous polyposis coli (APC, the best known tumor suppressor gene of human CRC, in 23 sporadic canine colorectal tumors, including 8 adenomas and 15 adenocarcinomas, via exon-resequencing analysis. As a comparison, we also performed the same sequencing analysis on 10 other genes, either located at human 5q22 (the same locus as APC or 18q21 (also frequently altered in human CRC, or known to play a role in human carcinogenesis. We noted that APC was the most significantly mutated gene in both canine adenomas and adenocarcinomas among the 11 genes examined. Significantly, we detected large deletions of ≥ 10 bases, many clustered near the mutation cluster region, as well as single or two base deletions in ~70% canine tumors of both subtypes. These observations indicate that like in the human, APC is also frequently altered in sporadic colorectal tumors in the dog and its alteration is an early event in canine colorectal tumorigenesis. Our study provides further evidence demonstrating the molecular similarity in pathogenesis between sporadic human and canine CRCs. This work, along with our previous copy number abnormality study, supports that sporadic canine CRCs are valid models of human CRCs at the molecular level.

  3. Cytological diagnostic of canine transmissible venereal tumor - Case report

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    Ulčar Igor

    2012-01-01

    Full Text Available Canine Transmissible Venereal Tumor (CTVT is a benign reticuloendothelial (histiocytic tumor of the dog that mainly affects the external genitalia. This tumor was found in male 2 years old mongrel dog. According the anamnestic data, there was no visible change of its general clinical status, except spontaneous bleeding with blood drops on the praeputium and the presence of blood in the urine. With clinical examination a multilobular mass on radix penis mucosa was found, which actually caused pseudohemorrhagia. The material for cytological diagnostic was taken with the imprint method and 4 cytological films were prepared and strained. The conclusion of the cytological diagnosis was CTVT. The tumor cause only local disturbances, and the differential diagnosis of the other "round cells tumors", histiocytomas, plasmacytomas, lymphoma, some melanomas and especially lymphosarcomas, which could be located on the external genitalia, had a big significance. Although some authors are mentioning spontaneous regression, however, because this is invasive tumor, a complete chirurgical excision was made.

  4. Survivin and related proteins in canine mammary tumors: immunohistochemical expression.

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    Bongiovanni, L; Romanucci, M; Malatesta, D; D'Andrea, A; Ciccarelli, A; Della Salda, L

    2015-03-01

    Survivin is reexpressed in most human breast cancers, where its expression has been associated with tumor aggressiveness, poor prognosis, and poor response to therapy. Survivin expression was evaluated in 41 malignant canine mammary tumors (CMTs) by immunohistochemistry, in relation to histological grade and stage, and correlated with that of some related molecules (β-catenin, caspase 3, heat shock proteins) to understand their possible role in canine mammary tumorigenesis. An increase in nuclear survivin expression, compared with healthy mammary glands, was observed in CMTs, where nuclear immunolabeling was related to the presence of necrosis. No statistically significant relation was found between the expression of the investigated molecules and the histological grade or stage. The present study may suggest an important involvement of survivin in CMT tumorigenesis. Its overexpression in most of the cases evaluated might suggest that targeting survivin in CMTs may be a valid anticancer therapy. PMID:24686389

  5. Immunohistochemical detection of estrogen receptors in canine mammary tumors

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    Elena Atanaskova Petrov

    2016-03-01

    Full Text Available Mammary tumors are among the most common neoplasms in intact female dogs.They have a complex morphology, usually affecting middle age and older bitches. Almost 50% of the mammary tumors in dogs are malignant neoplasms. Prognosis is based on several factors: stage, age, tumor size, metastasis, histopathology, ovariectomy status and hormone-receptor activity. Immunohistochemical (IHC measurement has become increasingly an important diagnostic and prognostic parameter, with the development of monoclonal antibodies against nuclear estrogen and progestin receptors. The aim of this study was to detect the presence of ER receptors in malignant canine mammary tumors and to identify their association with the clinical course of the tumor. Mammary tumor samples have been obtained by mastectomy from dogs presented at our clinic. Detailed clinical examination, CBC and basic serum biochemical profile were performed in all patients. Surgery was the only treatment. Histopathological examination and immunohistochemical detection of estrogen α receptors (ERα was performed on 8 formalin-fixed, paraffin-embedded tissue samples, using the PT LINK immunoperoxidase technique. Histopathological examination of the mammary tumor samples (n=11 revealed tubular adenocarcinoma (n=6,54.5% and ductal adenocarcinoma (n=3, 27.3%, one patient with benign adenoma and one with mastitis. Patients with positive ER tumors are alive, without remission, while 3 of the patients that were ER negative died due to lung metastases. According to our results, it can be concluded that the appearance and development of canine mammary tumors is highly connected with ovarian steroid hormones and that immunostaining of the tumors may be used as a good prognostic parameter in these patients.

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

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    Marconato Laura

    2009-03-01

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

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

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

    2015-11-01

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

  8. An overlooked tumor promoting immunoregulation by non-hematopoietic stromal cells.

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    Bose, Anamika; Ghosh, Tithi; Baral, Rathindranath

    2016-08-01

    Multidirectional complex communication between tumor-residing hematopoietic and non-hematopoietic stromal cells (NHSCs) decisively regulates cancer development, progression and therapeutic responses. HSCs predominantly participate in the immune regulations, while, NHSCs, provide parenchymal support or serve as a conduit for other cells or support angiogenesis. However, recent reports suggest NHSCs can additionally participate in ongoing tumor promoting immune reactions within tumor-microenvironment (TME). In this review, based on the state-of-art knowledge and accumulated evidence by us, we discuss the role of quite a few NHSCs in tumor from immunological perspectives. Understanding such consequence of NHSCs will surely pave the way in crafting effective cancer management. PMID:27311851

  9. Antigen profiling analysis of vaccinia virus injected canine tumors: oncolytic virus efficiency predicted by boolean models.

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    Cecil, Alexander; Gentschev, Ivaylo; Adelfinger, Marion; Nolte, Ingo; Dandekar, Thomas; Szalay, Aladar A

    2014-01-01

    Virotherapy on the basis of oncolytic vaccinia virus (VACV) strains is a novel approach for cancer therapy. In this study we describe for the first time the use of dynamic boolean modeling for tumor growth prediction of vaccinia virus GLV-1h68-injected canine tumors including canine mammary adenoma (ZMTH3), canine mammary carcinoma (MTH52c), canine prostate carcinoma (CT1258), and canine soft tissue sarcoma (STSA-1). Additionally, the STSA-1 xenografted mice were injected with either LIVP 1.1.1 or LIVP 5.1.1 vaccinia virus strains.   Antigen profiling data of the four different vaccinia virus-injected canine tumors were obtained, analyzed and used to calculate differences in the tumor growth signaling network by type and tumor type. Our model combines networks for apoptosis, MAPK, p53, WNT, Hedgehog, TK cell, Interferon, and Interleukin signaling networks. The in silico findings conform with in vivo findings of tumor growth. Boolean modeling describes tumor growth and remission semi-quantitatively with a good fit to the data obtained for all cancer type variants. At the same time it monitors all signaling activities as a basis for treatment planning according to antigen levels. Mitigation and elimination of VACV- susceptible tumor types as well as effects on the non-susceptible type CT1258 are predicted correctly. Thus the combination of Antigen profiling and semi-quantitative modeling optimizes the therapy already before its start.

  10. Recent progress in canine tumor vaccination: potential applications for human tumor vaccines.

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    Denies, Sofie; Sanders, Niek N

    2012-11-01

    Tumor vaccination holds great promise for the treatment of cancer and research concerning tumor vaccination in dogs is of great interest for veterinary as well as human medicine. Indeed, cancer is the leading cause of death in adult dogs and companion animals are acknowledged as excellent preclinical models for human oncology. The license of the veterinary melanoma vaccine (Oncept™) and Provenge® for the treatment of prostate cancer in men established tumor vaccination as a valid treatment modality for cancer. Although the results with this and other vaccines are promising, there are still some hurdles to overcome. In this article, preclinical and clinical trials with tumor vaccines in dogs are discussed, as well as the surplus value of canine cancer patients for human medicine. PMID:23249236

  11. Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors

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    Silvia Hennecke; Julia Beck; Kirsten Bornemann-Kolatzki; Stephan Neumann; Hugo Murua Escobar; Ingo Nolte; Susanne Conradine Hammer; Marion Hewicker-Trautwein; Johannes Junginger; Franz-Josef Kaup; Bertram Brenig; Ekkehard Schütz

    2015-01-01

    Background A somatic deletion at the proximal end of canine chromosome 27 (CFA27) was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5) and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors. Me...

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

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

    2016-04-01

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

  13. Evaluation of the kinase domain of c-KIT in canine cutaneous mast cell tumors

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    Kiupel Matti

    2006-04-01

    Full Text Available Abstract Background Mutations in the c-KIT proto-oncogene have been implicated in the progression of several neoplastic diseases, including gastrointestinal stromal tumors and mastocytosis in humans, and cutaneous mast cell tumors (MCTs in canines. Mutations in human mastocytosis patients primarily occur in c-KIT exon 17, which encodes a portion of its kinase domain. In contrast, deletions and internal tandem duplication (ITD mutations are found in the juxtamembrane domain of c-KIT in approximately 15% of canine MCTs. In addition, ITD c-KIT mutations are significantly associated with aberrant KIT protein localization in canine MCTs. However, some canine MCTs have aberrant KIT localization but lack ITD c-KIT mutations, suggesting that other mutations or other factors may be responsible for aberrant KIT localization in these tumors. Methods In order to characterize the prevalence of mutations in the phospho-transferase portion of c-KIT's kinase domain in canine MCTs exons 16–20 of 33 canine MCTs from 33 dogs were amplified and sequenced. Additionally, in order to determine if mutations in c-KIT exon 17 are responsible for aberrant KIT localization in MCTs that lack juxtamembrane domain c-KIT mutations, c-KIT exon 17 was amplified and sequenced from 18 canine MCTs that showed an aberrant KIT localization pattern but did not have ITD c-KIT mutations. Results No mutations or polymorphisms were identified in exons 16–20 of any of the MCTs examined. Conclusion In conclusion, mutations in the phospho-transferase portion of c-KIT's kinase domain do not play an important role in the progression of canine cutaneous MCTs, or in the aberrant localization of KIT in canine MCTs.

  14. Four cases of cell cannibalism in highly malignant feline and canine tumors.

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    Ferreira, Fernando Costa; Soares, Maria João; Carvalho, Sandra; Borralho, Liliana; Vicente, Gonçalo; Branco, Sandra; Correia, Jorge; Peleteiro, Maria Conceição

    2015-01-01

    Four cases of tumors in which cell internalization was frequently visualized are reported: one feline mammary carcinoma, one feline cutaneous squamous cell carcinoma, one canine pulmonary squamous cell carcinoma and one canine pleural mesothelioma. Cell internalization was observed by cytology in two of these cases (the feline mammary tumour and the pleural effusion in the canine mesothelioma) and by histopathology in all but the canine mesothelioma. Immunohistochemical staining for pancytokeratin was positive for both internalized and host cells, while E-cadherin expression was frequently absent, although internalized cells occasionally stained positive. This cell-to-cell interaction seems to be associated with tumors displaying a strong epithelial-mesenchymal transitional phenotype, in which cancer cells become engulfed by other cancer cells. Such event could be regarded as an important hallmark of very high malignancy. PMID:26525147

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

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

    2011-01-01

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

  16. Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.

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    Naoya Maekawa

    Full Text Available Programmed death 1 (PD-1, an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1, its ligand, together induce the "exhausted" status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1-expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed.

  17. Expression of p53 and CD44 in Canine Breast Tumor

    Institute of Scientific and Technical Information of China (English)

    LIU Yun; CUI Wen; CHENG Xi; FENG Xinchang

    2008-01-01

    The p53 and CD44 expression of 10 cases in canine breast tumor were examined utilizing immunohistochemical assay with rabbit anti-mouse polyclonal antibodies against p53 or CD44,respectively.The p53 expression was significantly higher in malignant than in benign breast tumor.The expression of CD44 was not significantly different in malignant breast cancer and benign breast tumor.This suggests that p53 can be used as an indicator for animal prognosis.

  18. The Role of c-KIT in Tumorigenesis: Evaluation in Canine Cutaneous Mast Cell Tumors

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    Joshua D. Webster

    2006-02-01

    Full Text Available The c-KIT proto-oncogene has been implicated in the pathogenesis of several neoplastic diseases, including gastrointestinal stromal tumors and mastocytosis in humans, and mast cell tumors (MCTs in canines. Cutaneous MCTs are common neoplasms in dogs and have a variable biologic behavior. The goal of this study was to define the prognostic significance of c-KIT mutations identified in canine MCTs and the associations between c-KIT mutations, KIT localization, and KIT expression levels. Microdissection and polymerase chain reaction were performed on 60 MCTs to identify c-KIT mutations. Anti-KIT antibodies were used for immunohistochemical evaluation of KIT localization. Forty-two MCTs were included in a tissue microarray, and KIT expression was quantified using immunofluorescence. Canine MCTs with c-KIT mutations were significantly associated with an increased incidence of recurrent disease and death. c-KIT mutations were also significantly associated with aberrant protein localization; however, the level of KIT expression did not correlate with either c-KIT mutations or changes in protein localization. Considering the high prevalence of canine MCTs and the central role of c-KIT in the tumorigenesis of certain tumors, canine MCTs are an excellent model for characterizing the role of c-KIT in neoplastic diseases and is a potential target for novel therapeutic agents in clinical trials.

  19. Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

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    Kim, Jong-Hyuk, E-mail: jhkim@umn.edu [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Frantz, Aric M.; Anderson, Katie L.; Graef, Ashley J.; Scott, Milcah C. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Robinson, Sally [Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Sharkey, Leslie C. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); O' Brien, Timothy D. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Dickerson, Erin B. [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Modiano, Jaime F., E-mail: modiano@umn.edu [Department of Veterinary Clinical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, MN (United States); Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States)

    2014-04-15

    Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into “IL-8 high” and “IL-8 low” groups. Genome-wide gene expression profiling showed that samples in the “IL-8 high” tumor group were enriched for genes associated with a “reactive microenvironment,” including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA. - Highlights: • IL-8 is expressed in canine hemangiosarcoma tumor samples and cell lines. • IL-8 transduces a relevant biological signal in canine hemangiosarcoma cells. • IL-8 gene signature is associated

  20. Interleukin-8 promotes canine hemangiosarcoma growth by regulating the tumor microenvironment

    International Nuclear Information System (INIS)

    Interleukin-8 (IL-8) gene expression is highly up-regulated in canine hemangiosarcoma (HSA); however, its role in the pathogenesis of this disease is unknown. We investigated the expression of IL-8 in canine HSA tissues and cell lines, as well and the effects of IL-8 on canine HSA in vitro, and in vivo using a mouse xenograft model for the latter. Constitutive expression of IL-8 mRNA, IL-8 protein, and IL-8 receptor were variable among different tumor samples and cell lines, but they showed stable steady states in each cell line. Upon the addition of IL-8, HSA cells showed transient intracellular calcium fluxes, suggesting that their IL-8 receptors are functional and that IL-8 binding activates relevant signaling pathways. Yet, neither addition of exogenous IL-8 nor blockade of endogenous IL-8 by neutralizing anti-IL-8 antibody (α-IL-8 Ab) affected HSA cell proliferation or survival in vitro. To assess potential effects of IL-8 in other tumor constituents, we stratified HSA cell lines and whole tumor samples into “IL-8 high” and “IL-8 low” groups. Genome-wide gene expression profiling showed that samples in the “IL-8 high” tumor group were enriched for genes associated with a “reactive microenvironment,” including activation of coagulation, inflammation, and fibrosis networks. Based on these findings, we hypothesized that the effects of IL-8 on these tumors were mostly indirect, regulating interactions with the microenvironment. This hypothesis was supported by in vivo xenograft experiments where survival and engraftment of tumor cells was inhibited by administration of neutralizing α-IL-8 Ab. Together, our results suggest that IL-8 contributes to establishing a permissive microenvironment during the early stages of tumorigenesis in HSA. - Highlights: • IL-8 is expressed in canine hemangiosarcoma tumor samples and cell lines. • IL-8 transduces a relevant biological signal in canine hemangiosarcoma cells. • IL-8 gene signature is associated

  1. Molecular imaging using Cu-ATSM and FDG in solid canine tumors

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    Hansen, Anders Elias

    Tumor hypoxia is one of the key factors in the development of aggressive and treatment resistant tumors. The negative effects of tumor hypoxia are mediated both by the direct lack of molecular oxygen for therapeutic efficacy and by pro- teomic and genomic changes induced in hypoxic tumor cells....... Identification of hypoxic tumor and intratumoral hypoxic regions therefore hold the potential to serve as a basis for individualized treatment protocols, including image guided radiation therapy. The current PhD project was undertaken to study tumor hypoxia in cancer bearing dogs, with the aims of 1) identifying...... the potential of implementing canine cancer patients in translational research on tumor hypoxia. 2) Non- invasively evaluate the hypoxia positron emission tomography (PET) tracer 64 Copper(II)diacetyl-bis(N 4 -methylthiosemicarbazone) ( 64 Cu-ATSM), including the comparison to non-invasive measures of tumor...

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

    DEFF Research Database (Denmark)

    Raposo-Ferreira, T M M; Bueno, R C; Terra, E M;

    2016-01-01

    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...... downregulation is involved in canine mammary gland tumorigenesis....

  3. Cox-2 levels in canine mammary tumors, including inflammatory mammary carcinoma: clinicopathological features and prognostic significance.

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    Queiroga, Felisbina Luisa; Perez-Alenza, Maria Dolores; Silvan, Gema; Peña, Laura; Lopes, Carlos; Illera, Juan Carlos

    2005-01-01

    Cyclo-oxygenase (Cox-2) plays an important role in mammary carcinogenesis, nevertheless, its role in canine mammary tumors, and particularly in inflammatory mammary carcinoma (IMC), is unknown. Tumor Cox-2 levels were analyzed by enzyme immunoassay, in post-surgical tumor homogenates of 129 mammary tumors (62 dysplasias and benign tumors, 57 malignant non-IMC and 10 IMC) from 57 female dogs. The highest Cox-2 values were detected in the IMC group. In non-IMC malignant tumors, high values of Cox-2 were related to skin ulceration (p IMC cases could indicate a special role of Cox-2 in the inflammatory phenotype and open the possibility of additional new therapeutic approaches in this special type of mammary cancer in humans and dogs.

  4. The role of osteoblasts in regulating hematopoietic stem cell activity and tumor metastasis

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    Neiva K.

    2005-01-01

    Full Text Available Bone marrow stromal cells are critical regulators of hematopoiesis. Osteoblasts are part of the stromal cell support system in bone marrow and may be derived from a common precursor. Several studies suggested that osteoblasts regulate hematopoiesis, yet the entire mechanism is not understood. It is clear, however, that both hematopoietic precursors and osteoblasts interact for the production of osteoclasts and the activation of resorption. We observed that hematopoietic stem cells (HSCs regulate osteoblastic secretion of various growth factors, and that osteoblasts express some soluble factors exclusively in the presence of HSCs. Osteoblasts and hematopoietic cells are closely associated with each other in the bone marrow, suggesting a reciprocal relationship between them to develop the HSC niche. One critical component regulating the niche is stromal-derived factor-1 (SDF-1 and its receptor CXCR4 which regulates stem cell homing and, as we have recently demonstrated, plays a crucial role in facilitating those tumors which metastasize to bone. Osteoblasts produce abundant amounts of SDF-1 and therefore osteoblasts play an important role in metastasis. These findings are discussed in the context of the role of osteoblasts in marrow function in health and disease.

  5. Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11

    International Nuclear Information System (INIS)

    Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms in the gastrointestinal tract of humans and dogs. Little is known about the pathogenesis of these tumors. This study evaluated the role of c-KIT in canine GISTs; specifically, we investigated activating mutations in exons 8, 9, 11, 13, and 17 of c-KIT and exons 12, 14, and 18 of platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), all of which have been implicated in human GISTs. Seventeen canine GISTs all confirmed to be positive for KIT immunostaining were studied. Exons 8, 9, 11, 13 and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA, were amplified from DNA isolated from formalin-fixed paraffin-embedded samples. Of these seventeen cases, six amplicons of exon 11 of c-KIT showed aberrant bands on gel electrophoresis. Sequencing of these amplicons revealed heterozygous in-frame deletions in six cases. The mutations include two different but overlapping six base pair deletions. Exons 8, 9, 13, and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA had no abnormalities detected by electrophoresis and sequencing did not reveal any mutations, other than synonymous single nucleotide polymorphisms (SNPs) found in exon 11 of c-KIT and exons 12 and 14 of PDGFRA. The deletion mutations detected in canine GISTs are similar to those previously found in the juxtamembrane domain of c-KIT in canine cutaneous mast cell tumors in our laboratory as well as to those reported in human GISTs. Interestingly, none of the other c-KIT or PDGFRA exons showed any abnormalities in our cases. This finding underlines the critical importance of c-KIT in the pathophysiology of canine GISTs. The expression of KIT and the identification of these activating mutations in c-KIT implicate KIT in the pathogenesis of these tumors. Our results indicate that mutations in c-KIT may be of prognostic significance and that targeting KIT may be a rational approach to treatment of these malignant tumors. This study further

  6. Hematopoietic tumors of the female genital system: imaging features with pathologic correlation.

    Science.gov (United States)

    Salem, Usama; Menias, Christine O; Shaaban, Akram; Bhosale, Priya R; Youssef, Ayda; Elsayes, Khaled M

    2014-08-01

    Various hematopoietic neoplasms can involve the female genital system. The most common hematological malignancy that involves the female genital system is lymphoma and secondary involvement is more common than primary genital lymphoma. Rarely, leukemic infiltration and extramedullary plasmacytomas of the female genital tract may also occur. Being infrequent, these lesions are commonly misdiagnosed radiologically. Therefore, understanding these malignancies of the female genital system and recognizing their imaging features are of utmost clinical importance. Although definitive diagnosis can be made only by histological analysis, imaging of these tumors plays an important role in detecting lesion extensions, guiding biopsies, staging disease, planning therapy, and detecting recurrence.

  7. c-erbB-2 expression and nuclear pleomorphism in canine mammary tumors

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    Dutra A.P.

    2004-01-01

    Full Text Available The objective of the present investigation was to study the expression of c-erbB-2 and MIB-1 and try to associate them with morphological features of the cell such as nuclear pleomorphism, mitotic count and histological grade in a series of 70 canine mammary gland tumors, 22 of them benign and 48 malignant. Tumors were collected at the Veterinary Hospital of UFMG (Brazil and the Veterinary Faculty of Porto University (Portugal. c-erbB-2 expression was determined according to the guidelines provided by the manufacturer of the HercepTest system and nuclear pleomorphism, mitotic count and histological grade according the Elston and Ellis grading system. The HercepTest is the FDA-approved in vitro diagnostic test marketed by Dako. It is a semi-quantitative immunohistochemical assay used to determine overexpression of HER2 protein (human epidermal growth factor receptor in breast cancer tissue. MIB-1 expression was also evaluated in 28 malignant tumors. Seventeen (35.4% of the malignant tumors were positive for c-erbB-2 expression, which was positively associated with nuclear pleomorphism (P < 0.0001, histological grade (P = 0.0017 and mitotic count (P < 0.05. Nuclear pleomorphism also showed a positive association with MIB-1 index (P < 0.0001. These results suggest that some of the biological and morphological characteristics of the tumor are associated in canine mammary gland tumors, as also reported for human breast cancer. It was also possible to show that the immunoexpression of c-erbB-2 can be a factor in mammary carcinogenesis. This fact opens the possibility of using anti-c-erbB-2 antibodies in the treatment of canine mammary tumors.

  8. Immunohistochemical study of genital and extragenital forms of canine transmissible venereal tumor in Brazil

    OpenAIRE

    Mariana B. Mascarenhas; Paulo V. Peixoto; Regina R. Ramadinha; Elise M. Yamasaki; Samay Z.R. Costa; David Driemeier; Luciana Sonne; Ticiana N. França

    2014-01-01

    Aiming to provide insight and discussing the problems related to the diagnosis and differential diagnosis of canine transmissible venereal tumor (CTVT), especially in its extragenital form, immunohistochemical evaluation was performed and a comparison was established by analysis of the microscopic appearance of 10 genital CTVTs and 13 exclusively extragenital CTVTs previously diagnosed by cytology and histopathology. CTVTs samples were incubated with biotinylated antibodies raised against spe...

  9. Prevalence of the Prefoldin Subunit 5 Gene Deletion in Canine Mammary Tumors.

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    Silvia Hennecke

    Full Text Available A somatic deletion at the proximal end of canine chromosome 27 (CFA27 was recently reported in 50% of malignant mammary tumors. This region harbours the tumor suppressor gene prefoldin subunit 5 (PFDN5 and the deletion correlated with a higher Ki-67 score. PFDN5 has been described to repress c-MYC and is, therefore, a candidate tumor-suppressor and cancer-driver gene in canine mammary cancer. Aim of this study was to confirm the recurrent deletion in a larger number of tumors.Droplet digital PCR for PFDN5 was performed in DNA from 102 malignant, 40 benign mammary tumors/dysplasias, 11 non-neoplastic mammary tissues and each corresponding genomic DNA from leukocytes. The copy number of PFDN5 was normalized to a reference amplicon on canine chromosome 32 (CFA32. Z-scores were calculated, based on Gaussian distributed normalized PFDN5 copy numbers of the leukocyte DNA. Z-scores ≤ -3.0 in tissue were considered as being indicative of the PFDN5 deletion and called as such. The Ki-67 proliferation index was assessed in a subset of 79 tissue samples by immunohistochemistry.The deletion was confirmed in 24% of all malignant tumors, detected in only 7.5% of the benign tumors and was not present in any normal mammary tissue sample. The subgroup of solid carcinomas (n = 9 showed the highest frequency of the deletion (67% and those malignomas without microscopical high fraction of benign tissue (n = 71 had a 32% frequency (p<0.01 vs. benign samples. The Ki-67 score was found to be significantly higher (p<0.05 in the PFDN5-deleted group compared to malignant tumors without the deletion.A somatic deletion of the PFDN5 gene is recurrently present in canine mammary cancer, supporting a potential role in carcinogenesis. The association of this deletion with higher Ki-67 indicates an increased proliferation rate and thus a link to tumor aggressiveness can be hypothesized. The confirmation of earlier results warrants further studies on PFDN5 as cancer

  10. Steroid Tumor Environment in Male and Female Mice Model of Canine and Human Inflammatory Breast Cancer

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    Sara Caceres

    2016-01-01

    Full Text Available Canine inflammatory mammary cancer (IMC shares clinical and histopathological characteristics with human inflammatory breast cancer (IBC and has been proposed as a good model for studying the human disease. The aim of this study was to evaluate the capacity of female and male mice to reproduce IMC and IBC tumors and identify the hormonal tumor environment. To perform the study sixty 6–8-week-old male and female mice were inoculated subcutaneously with a suspension of 106 IPC-366 and SUM149 cells. Tumors and serum were collected and used for hormonal analysis. Results revealed that IPC-366 reproduced tumors in 90% of males inoculated after 2 weeks compared with 100% of females that reproduced tumor at the same time. SUM149 reproduced tumors in 40% of males instead of 80% of females that reproduced tumors after 4 weeks. Both cell lines produce distant metastasis in lungs being higher than the metastatic rates in females. EIA analysis revealed that male tumors had higher T and SO4E1 concentrations compared to female tumors. Serum steroid levels were lower than those found in tumors. In conclusion, IBC and IMC male mouse model is useful as a tool for IBC research and those circulating estrogens and intratumoral hormonal levels are crucial in the development and progression of tumors.

  11. Steroid Tumor Environment in Male and Female Mice Model of Canine and Human Inflammatory Breast Cancer.

    Science.gov (United States)

    Caceres, Sara; Peña, Laura; Silvan, Gema; Illera, Maria J; Woodward, Wendy A; Reuben, James M; Illera, Juan C

    2016-01-01

    Canine inflammatory mammary cancer (IMC) shares clinical and histopathological characteristics with human inflammatory breast cancer (IBC) and has been proposed as a good model for studying the human disease. The aim of this study was to evaluate the capacity of female and male mice to reproduce IMC and IBC tumors and identify the hormonal tumor environment. To perform the study sixty 6-8-week-old male and female mice were inoculated subcutaneously with a suspension of 10(6)IPC-366 and SUM149 cells. Tumors and serum were collected and used for hormonal analysis. Results revealed that IPC-366 reproduced tumors in 90% of males inoculated after 2 weeks compared with 100% of females that reproduced tumor at the same time. SUM149 reproduced tumors in 40% of males instead of 80% of females that reproduced tumors after 4 weeks. Both cell lines produce distant metastasis in lungs being higher than the metastatic rates in females. EIA analysis revealed that male tumors had higher T and SO4E1 concentrations compared to female tumors. Serum steroid levels were lower than those found in tumors. In conclusion, IBC and IMC male mouse model is useful as a tool for IBC research and those circulating estrogens and intratumoral hormonal levels are crucial in the development and progression of tumors. PMID:27195300

  12. TP53 Polymorphisms allow for genetic sub-grouping of the canine transmissible venereal tumor

    Science.gov (United States)

    Sánchez-Servín, Abel; Córdova-Alarcon, Emilio; Fajardo, Raúl

    2009-01-01

    The canine transmissible venereal tumor (CTVT) is found mainly in dogs' sexual organs. Currently, it is widely accepted that all samples of CTVT show similar histopathological characteristics and share common genetic alterations. Despite the common genetic origin of CTVT, mutations in the P53 gene have been reported. In this study, we proposed that tumor samples can be genetically grouped using this gene. The presence of different subgroups of CTVT was determined in Mexican dogs using the TP53 gene sequence in CTVT samples. Four new polymorphisms were found and therefore, the CTVT samples were classified in five subgroups. PMID:19934603

  13. Immunohistochemical and molecular expression of laminin-332 gamma-2 chain in canine mammary tumors

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    D.A.P.C Zuccari

    2011-02-01

    Full Text Available Forty-eight cases of canine mammary cancer were investigated to evaluate the immunohistochemical distribution of the γ2 chain of laminin-332. Tumor cells were compared to a pool of normal mammary tissues using quantitative RT-PCR. The western blot was performed in eight tumor samples as complementary test to evaluate protein integrity. Immunohistochemistry experiments showed negative, focal, and weak expression of laminin-332 γ2 in tumors with the worst prognosis. Quantitative PCR revealed downregulation of the gene in 27 (56.2% of the animals. Out of the 16 dogs with γ2 chain overexpression, seven were still alive. The western blot results showed bands generation of 36, 50, and 98kDa, suggesting degradation of laminin-332 γ2 in malignant tumors. The results suggest that, in the future, low expression and/or degradation of laminin-332 γ2 chain in canine mammary tumors may be used as an indicator of malignant potential. However, further studies are necessary to corroborate these results

  14. New agents for targeting of IL-13RA2 expressed in primary human and canine brain tumors.

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    Waldemar Debinski

    Full Text Available Interleukin 13 receptor alpha 2 (IL-13RA2 is over-expressed in a vast majority of human patients with high-grade astrocytomas like glioblastoma. Spontaneous astrocytomas in dogs resemble human disease and have been proposed as translational model system for investigation of novel therapeutic strategies for brain tumors. We have generated reagents for both detection and therapeutic targeting of IL-13RA2 in human and canine brain tumors. Peptides from three different regions of IL-13RA2 with 100% sequence identity between human and canine receptors were used as immunogens for generation of monoclonal antibodies. Recombinant canine mutant IL-13 (canIL-13.E13K and canIL-13.E13K based cytotoxin were also produced. The antibodies were examined for their immunoreactivities in western blots, immunohistochemistry, immunofluorescence and cell binding assays using human and canine tumor specimen sections, tissue lysates and established cell lines; the cytotoxin was tested for specific cell killing. Several isolated MAbs were immunoreactive to IL-13RA2 in western blots of cell and tissue lysates from glioblastomas from both human and canine patients. Human and canine astrocytomas and oligodendrogliomas were also positive for IL-13RA2 to various degrees. Interestingly, both human and canine meningiomas also exhibited strong reactivity. Normal human and canine brain samples were virtually negative for IL-13RA2 using the newly generated MAbs. MAb 1E10B9 uniquely worked on tissue specimens and western blots, bound live cells and was internalized in GBM cells over-expressing IL-13RA2. The canIL-13.E13K cytotoxin was very potent and specific in killing canine GBM cell lines. Thus, we have obtained several monoclonal antibodies against IL-13RA2 cross-reacting with human and canine receptors. In addition to GBM, other brain tumors, such as high grade oligodendrogliomas, meningiomas and canine choroid plexus papillomas, appear to express the receptor at high levels

  15. Canine parvovirus-like particles, a novel nanomaterial for tumor targeting

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    Destito Giuseppe

    2006-02-01

    Full Text Available Abstract Specific targeting of tumor cells is an important goal for the design of nanotherapeutics for the treatment of cancer. Recently, viruses have been explored as nano-containers for specific targeting applications, however these systems typically require modification of the virus surface using chemical or genetic means to achieve tumor-specific delivery. Interestingly, there exists a subset of viruses with natural affinity for receptors on tumor cells that could be exploited for nanotechnology applications. For example, the canine parvovirus (CPV utilizes transferrin receptors (TfRs for binding and cell entry into canine as well as human cells. TfRs are over-expressed by a variety of tumor cells and are widely being investigated for tumor-targeted drug delivery. We explored whether the natural tropism of CPV to TfRs could be harnessed for targeting tumor cells. Towards this goal, CPV virus-like particles (VLPs produced by expression of the CPV-VP2 capsid protein in a baculovirus expression system were examined for attachment of small molecules and delivery to tumor cells. Structural modeling suggested that six lysines per VP2 subunit are presumably addressable for bioconjugation on the CPV capsid exterior. Between 45 and 100 of the possible 360 lysines/particle could be routinely derivatized with dye molecules depending on the conjugation conditions. Dye conjugation also demonstrated that the CPV-VLPs could withstand conditions for chemical modification on lysines. Attachment of fluorescent dyes neither impaired binding to the TfRs nor affected internalization of the 26 nm-sized VLPs into several human tumor cell lines. CPV-VLPs therefore exhibit highly favorable characteristics for development as a novel nanomaterial for tumor targeting.

  16. Pathogenesis of canine cortisol-secreting adrenocortical tumors

    NARCIS (Netherlands)

    Kool, Miriam

    2015-01-01

    In dogs, hypercortisolism is one of the most frequently observed endocrine disorders, with an estimated incidence of about 1-2 cases per 1000 dogs per year. Approximately 15% of these cases is due to a cortisol-secreting adrenocortical tumor (AT). Cortisol-secreting ATs are characterized by uncontro

  17. Sumoylation is tumor-suppressive and confers proliferative quiescence to hematopoietic progenitors in Drosophila melanogaster larvae

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    Marta E. Kalamarz

    2011-12-01

    How cell-intrinsic regulation of the cell cycle and the extrinsic influence of the niche converge to provide proliferative quiescence, safeguard tissue integrity, and provide avenues to stop stem cells from giving rise to tumors is a major challenge in gene therapy and tissue engineering. We explore this question in sumoylation-deficient mutants of Drosophila. In wild type third instar larval lymph glands, a group of hematopoietic stem/progenitor cells acquires quiescence; a multicellular niche supports their undifferentiated state. However, how proliferative quiescence is instilled in this population is not understood. We show that Ubc9 protein is nuclear in this population. Loss of the SUMO-activating E1 enzyme, Aos1/Uba2, the conjugating E2 enzyme, Ubc9, or the E3 SUMO ligase, PIAS, results in a failure of progenitors to quiesce; progenitors become hyperplastic, misdifferentiate, and develop into microtumors that eventually detach from the dorsal vessel. Significantly, dysplasia and lethality of Ubc9 mutants are rescued when Ubc9wt is provided specifically in the progenitor populations, but not when it is provided in the niche or in the differentiated cortex. While normal progenitors express high levels of the Drosophila cyclin-dependent kinase inhibitor p21 homolog, Dacapo, the corresponding overgrown mutant population exhibits a marked reduction in Dacapo. Forced expression of either Dacapo or human p21 in progenitors shrinks this population. The selective expression of either protein in mutant progenitor cells, but not in other hematopoietic populations, limits overgrowth, blocks tumorogenesis, and restores organ integrity. We discuss an essential and complex role for sumoylation in preserving the hematopoietic progenitor states for stress response and in the context of normal development of the fly.

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

    Science.gov (United States)

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

    2015-10-01

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

  19. Canine mast cell tumors: diagnosis, treatment, and prognosis

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    Garrett LD

    2014-08-01

    Full Text Available Laura D Garrett Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, IL, USA Abstract: Mast cell tumors (MCTs are the most common malignant skin cancer in dogs, and significant variability exists in their biological behavior. Most MCTs are cured with appropriate local therapy, but a subset shows malignant behavior with the potential to spread to lymph nodes, liver, spleen, and other areas and to thus become a systemic cancer. Because of this variable behavior, it is difficult to predict how any individual tumor is going to behave. The variability thus creates uncertainty in deciding what a particular dog's prognosis is, whether staging tests to assess for metastasis are needed, and even what treatments will be necessary for best outcome. In addition to controversies over the potential for development of systemic disease, or diffuse metastasis, controversies also exist over what treatment is needed to best attain local control of these tumors. This article will briefly discuss the diagnosis of MCTs in dogs and will summarize the literature in regards to the controversial topics surrounding the more aggressive form of this disease, with recommendations made based on published studies. Keywords: mitotic index, mastocytosis, tyrosine kinase inhibitor, histologic grade

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

    Science.gov (United States)

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

    2015-10-01

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

  1. Spontaneous skin canine tumors: toluidine blue stain detection of mast cells in tissue section

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    ALKETA QOKU

    2014-06-01

    Full Text Available Dog mast cell tumor (MCT is common in dog. The etiology of canine MCTs is unknown, but it is probably multi-factorial. Its incidence is higher than it has found in human. There are demonstrated several common biological and clinical characteristics in both species. Cutaneous mast cells are located in the dermis and hypodermis. The objective of this study is to detect of MC on Toluidine Blue stained slides. There were examined 74 dogs of difference breeds and aged, from Tirana city. Six of them demonstrated the skin canine tumors. Skin samples were obtained from these animals. Macroscopic examination of the tumor revealed nodular ulcerated lesion with areas of necrosis and hemorrhage, accompanied with normal superjacent epidermis and annexes. Serial sections obtained from biopsy specimens were processed with toluidine blue staining pH 4.5, specific for MC identification. This study suggests that Toluidine blue, pH 4.5 stain may give a good information about skin tumors in dog, histologically with benign behavior.

  2. Immunohistochemical identification of myoepithelial, epithelial, and connective tissue cells in canine mammary tumors.

    Science.gov (United States)

    Destexhe, E; Lespagnard, L; Degeyter, M; Heymann, R; Coignoul, F

    1993-03-01

    Fifty-eight formalin-fixed paraffin-embedded canine mammary tumors, 19 malignant and 39 benign, were used in this study. Tumors were obtained from dogs submitted for surgical resection of lesions at private veterinary practices in Brussels or from the surgery unit of the Faculty of Veterinary Medicine, University of Liège. Immunohistochemical evaluation was performed, using monoclonal antibodies directed against keratins 8-18 and 19, vimentin, desmin, and alpha-actin and polyclonal antibodies directed against high-molecular-weight keratins and S-100 protein. The main cell types, epithelial, myoepithelial, and connective, were identified, and myoepithelial cells represented the major component of most tumors, both benign and malignant. Myoepithelial cells had five patterns: resting and proliferative suprabasal cells, spindle and star-shaped interstitial cells, and cartilage. Reactivity to keratin 19, vimentin, alpha-actin, and S-100 protein suggested a progressive transformation from resting cells to cartilage. Epithelial cell reactivities were limited to keratins; only keratinized cells were positive for polyclonal keratins. Myofibroblasts were positive for both vimentin and alpha-actin, and connective tissue cells were positive for vimentin. Myoepithelial cells appeared to be the major component of carcinomas, justifying reevaluation and simplification of histomorphologic classifications, with a "pleomorphic carcinoma" group including all carcinomas except squamous, mucinous, and comedo carcinomas. Immunohistochemical evaluation, in addition to routine hematoxylin and eosin histopathologic evaluation is recommended for precise classification of canine mammary tumors. PMID:7682367

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

    Science.gov (United States)

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

    2014-01-01

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

  4. 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.

  5. Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

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    Citro Gennaro

    2008-11-01

    Full Text Available Abstract Sticker's sarcoma (also known as transmissible venereal tumor is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT, treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy. Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 μs each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

  6. Roles of DNA mutation in the coding region and DNA methylation in the 5' flanking region of BRCA1 in canine mammary tumors.

    Science.gov (United States)

    Qiu, Hengbin; Lin, Deigui

    2016-07-01

    The Breast cancer 1, early onset gene (BRCA1) is known to be significantly associated with human familial breast cancer and is identified to play an important role in canine mammary tumors. Here, genetic variations in the coding region and DNA methylation in the 5' flanking region of BRCA1 in canine mammary tumor samples, 15 each of benign and malignant against 10 normal canine mammary tissue samples, were analyzed using the direct sequencing method. The results indicated two point mutations each in the coding region of canine BRCA1 in one benign mammary tumor sample (4702G >T and 4765G >T) and in one malignant canine mammary tumor sample (3619A >G and 4006G >A). No mutations were detected in the normal canine mammary tissue samples. The 4702G >T mutation was found to terminate further translation. The physical effect of the 4765G >T mutation was found to be the repalacement of the glutamate residue with glutamine. The physical effect of the 3619A >G mutation was found to be the replacement of the threonine residue with alanine, and that of mutation 4006G >A was the replacement of the valine residue with isoleucine in the BRCA1 protein. Bisulfite sequencing detected methylated CpG sites in one canine malignant mammary tumor sample. In conclusion, the present study elucidated the mutational status of the BRCA1 coding region and methylation status of the 5' flanking region of BRCA1 in canine mammary tumors. PMID:26888582

  7. Alternativas Terapéuticas en las neoplasias vesicales caninas Therapeutic options in canine bladder tumors

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    R.L. Rovere

    2002-01-01

    Full Text Available Las neoplasias vesicales en caninos representan menos del 1% de los tumores presentes en esta especie. El tratamiento quirúrgico se indica en tumores benignos y como complemento de la quimioterapia y radioterapia. Para la quimioterapia se emplean más frecuentemente la doxorrubicina, el 5-fluorouracilo, la ciclofosfamida, la vincristina y cisplatino. La asociación de la doxorrubicina-ciclofosfamida por vía sistémica en asociación con el cisplatino intravesical, sería un tratamiento recomendable, en particular en los casos de carcinoma de células de transiciónThe canine urinary bladder tumors represent less than 1% of all tumors present in this species. Surgical treatment is indicated in benign tumors and combined with chemotherapy or radiotherapy. Doxorubicin, 5 fluorouracil, cyclophosphamide, vincristine and cisplatin are the drugs mostly used for chemotherapy. Systemic Doxorubicin-ciclophosphamide therapy in association with intravesical cisplatin therapy are recommended, particularly in transitional cell carcinoma

  8. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

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    Bradshaw, Tyler J. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bowen, Stephen R. [Departments of Radiation Oncology and Radiology, University of Washington, Seattle, Washington (United States); Deveau, Michael A. [Department of Small Animal Clinical Sciences, Texas A& M University, College Station, Texas (United States); Kubicek, Lyndsay [Angell Animal Medical Center, Boston, Massachusetts (United States); White, Pamela [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bentzen, Søren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Chappell, Richard J. [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Forrest, Lisa J. [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Jeraj, Robert, E-mail: rjeraj@wisc.edu [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States)

    2015-03-15

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV{sub max}; SUV{sub mean}) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R{sup 2}. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV{sub mean} (P=.018), and midtreatment FLT SUV{sub max} (P=.006). Large decreases in FLT SUV{sub mean} from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV{sub max} (P=.022) in

  9. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    International Nuclear Information System (INIS)

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUVmax; SUVmean) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R2. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUVmean (P=.018), and midtreatment FLT SUVmax (P=.006). Large decreases in FLT SUVmean from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUVmax (P=.022) in combination with large FLT response from

  10. A benchmark analysis of radiation flux distribution for Boron Neutron Capture Therapy of canine brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Moran, J.M.

    1992-02-01

    Calculations of radiation flux and dose distributions for Boron Neutron Capture Therapy (BNCT) of brain tumors are typically performed using sophisticated three-dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly-heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This work describes a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador Retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador Retriever head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for the model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous tissue model. Comparison of the results showed that the peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models.

  11. A benchmark analysis of radiation flux distribution for Boron Neutron Capture Therapy of canine brain tumors

    International Nuclear Information System (INIS)

    Calculations of radiation flux and dose distributions for Boron Neutron Capture Therapy (BNCT) of brain tumors are typically performed using sophisticated three-dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly-heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This work describes a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador Retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador Retriever head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for the model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous tissue model. Comparison of the results showed that the peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models

  12. Immunohistochemical study of genital and extragenital forms of canine transmissible venereal tumor in Brazil

    Directory of Open Access Journals (Sweden)

    Mariana B. Mascarenhas

    2014-03-01

    Full Text Available Aiming to provide insight and discussing the problems related to the diagnosis and differential diagnosis of canine transmissible venereal tumor (CTVT, especially in its extragenital form, immunohistochemical evaluation was performed and a comparison was established by analysis of the microscopic appearance of 10 genital CTVTs and 13 exclusively extragenital CTVTs previously diagnosed by cytology and histopathology. CTVTs samples were incubated with biotinylated antibodies raised against specific membrane (anti-macrophage and cytoplasmic antigens (anti-lysozyme, anti-S-100 protein, anti-vimentin and anti-CD18 and subsequently developed using streptavidin-biotin peroxidase and streptavidin-biotin-alkaline phosphatase methods. A strong reactivity with the anti-vimentin antibody was found in 100% of the tumors tested (22/22. No reactivity was found for the anti-lysozyme, anti-macrophage, anti-S-100 protein and anti-CD18. No histopathological or immunoreactivity differences between genital and extragenital CTVTs were found. These findings do not corroborate the hypothesis of histiocytic origin of CTVT (no reactivity to anti-lysozyme, anti-macrophage and anti-CD 18 antibodies. In addition, the antibody panel used is useful to narrow the differential diagnosis for lymphomas, histiocytic tumors, amelanotic melanomas, and poorly differentiated epithelial neoplasias, among others.

  13. Transrectal ultrasound-integrated spectral optical tomography of hypoxic progression of a regressing tumor in a canine prostate.

    Science.gov (United States)

    Jiang, Z; Piao, D; Bartels, K E; Holyoak, G R; Ritchey, J W; Ownby, C L; Rock, K; Slobodov, G

    2011-12-01

    The objective of this study was to evaluate if transrectal optical tomography implemented at three wavelength bands for spectral detection could monitor changes of the hemoglobin oxygen saturation (StO2) in addition to those of the total hemoglobin concentration ([HbT]) in lesions of a canine prostate, including an induced tumor modeling canine prostate cancer. Near-infrared (NIR) optical tomography was integrated with ultrasound (US) for transrectal imaging. Multi-spectral detection at 705_nm, 785_nm and 808_nm rendered measurements of [HbT] and StO2. Canine transmissible venereal tumor (TVT) cells were injected into the right lobe of a dog's prostate gland, which had a pre-existing cyst in the left lobe. Longitudinal assessments of the prostate were performed weekly over a 63-day duration by NIR imaging concurrent with grey-scale and Doppler US. Ultrasonography revealed a bi-lobular tumor-mass regressing from day-49 to day-63. At day-49 this tumor-mass developed a hypoxic core that became larger and more intense by day-56 and expanded further by day-63. The tumor-mass presented a strong hyper-[HbT] feature on day-56 that was inconsistent with US-visualized blood flow. Histology confirmed two necrotic TVT foci within this tumor-mass. The cyst appeared to have a large anoxic-like interior that was greater in size than its ultrasonographically delineated lesion, and a weak lesional elevation of [HbT]. On day-56, the cyst presented a strong hyper-[HbT] feature consistent with US-resolved blood flow. Histology revealed acute and chronic hemorrhage in the periphery of the cyst. The NIR imaging features of two other TVT nodules and a metastatic lymph node were evaluated retrospectively. Transrectal US-integrated spectral optical tomography seems to enable longitudinal monitoring of intra-lesional oxygenation dynamics in addition to the hemoglobin content of lesions in the canine prostate.

  14. Downregulation of the KLF4 transcription factor inhibits the proliferation and migration of canine mammary tumor cells.

    Science.gov (United States)

    Tien, Yung-Tien; Chang, Mei-Hsien; Chu, Pei-Yi; Lin, Chen-Si; Liu, Chen-Hsuan; Liao, Albert T

    2015-08-01

    Canine mammary tumor (CMT) is the most common neoplasm in female dogs, and over 50% of CMTs are diagnosed as malignant. Krüppel-like factor 4 (KLF4) is a member of the KLF family of transcription factors and is associated with cell proliferation, differentiation, migration, and apoptosis. Although the role of KLF4 is still controversial in various human cancers, KLF4 has been identified as an oncogene in human breast cancer. Moreover, high KLF4 expression is correlated with an aggressive phenotype in CMT. Therefore, investigating the function of KLF4 may help better understand the pathogenesis of CMT. In this study, partial sequences of canine KLF4 and KLF4 expression were identified in various normal canine tissues, as well as CMT cells and Madin-Darby canine kidney (MDCK) cells. Kenpaullone, a small molecule inhibitor of KLF4, downregulated KLF4 expression in CMT cells and reduced CMT cell proliferation, migration, and colony formation in soft agar. Kenpaullone treatment induced S and G2/M phase arrest in CMT and MDCK cells, and induced death in CMT cells, but not in MDCK cells. It was concluded that KLF4 is expressed in various normal canine tissues, and downregulation of KLF4 inhibited CMT cell proliferation and migration, and induced cell death. The results of this study suggest that KLF4 may represent a suitable therapeutic target for CMT therapy. PMID:25616642

  15. Effect of Spirulina Platensis Polysaccharide on Hematopoietic Recovery and Related Cytokines in Mice with Transplanted Tumor Treated by Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    刘晓梅; 张洪泉

    2002-01-01

    Objective:To evaluate the effect of Spirulina platensis polysaccharide (SPP) on hematopoietic recovery and related cytokines in mice with transplanted tumor after chemotherapy. Methods:Mouse model of transplanted solid tumor was established and treated with chemotherapy. Peripheral blood cells, bone marrow nucleated cells, and colony forming unit-spleen (CFU-S) were counted; the content of DNA in bone marrow was inspected by ultraviolet spectrophotometer; serum content of cytokines, interleukin (IL)1, IL-3, granulocyte-macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor-α (TNF-α) were determined by double antibody sandwich ELISA.Results:Cyclophosphamide (CTX) could induce evident myelosuppression, manifested as decrease of peripheral blood cells, bone marrow nucleated cell and DNA, and the CFU-S number. SPP could significantly ameliorate the myelosuppression induced by CTX without reducing anti-tumor effect of CTX. In addition, it could also increase the contents of IL-1, IL-3, GM-CSF, TNF-α in serum. Conclusion:SPP can probably accelerate the hematopoietic recovery in mice after chemotherapy through promoting endogenous secretion of cytokines.

  16. Postsplenectomy sclerosing extramedullary hematopoietic tumor with unexpected good clinical evolution: morphologic, immunohistochemical, and molecular analysis of one case and review of the literature.

    Science.gov (United States)

    Gualco, Gabriela; Ojopi, Elida B P; Chioato, Lucimara; Cordeiro, Danielle Leão; Negretti, Fabio; Bacchi, Carlos E

    2010-05-01

    Sclerosing extramedullary hematopoietic tumor has been described as a rare manifestation of chronic myeloproliferative neoplasm. The lack of knowledge about this entity has caused it to be mistaken for many types of nonhematopoietic and hematopoietic tumors. We present the case of a 71-year-old lady with a long history of primary myelofibrosis, which developed multiple abdominal sclerosing extramedullary hematopoietic tumors with good clinical evolution. Nonchronic myeloid leukemia myeloproliferative neoplasm included a JAK2 mutation as part of the diagnosis algorithm. Particularly, idiopathic myelofibrosis is related with a JAK2 mutation in 50% of the cases with a pejorative prognosis. The absence of JAK2 demonstrated in the paraffin samples of the tumors may be related to the unusual evolution in this particular case. Morphologically differential diagnoses considered in the evaluation of this entity and in our case included sarcomas mainly liposarcoma, anaplastic carcinoma, and Hodgkin lymphoma.

  17. Detection of mutations within exons 4 to 8 of the p53 tumor suppressor gene in canine mammary glands

    Directory of Open Access Journals (Sweden)

    D.M.B. Souza

    2012-04-01

    Full Text Available Fifteen female canines with mammary tumors and 6 normal females were used to study mutations in exons 4 to 8 of the p53 gene. DNA samples from the tumors, respective adjacent normal mammary tissue and mammary glands from healthy animals were sequenced and analyzed for the presence of mutations. Mutations were found in 71.8% of the samples and the most frequent were missense mutations. The most attacked exons in the mammary tumor were 5, 7 and 8, with 23.4, 31.6 and 23.4% mutations, respectively. Canine mammary tumors are related to mutations in gene p53 and mutations mostly occur in the region of the protein that is linked to the DNA in the cell nucleus, which can change the functionality of the cell and propitiate tumor growth. Despite being macroscopically normal, the mammary tissue adjacent to the tumors has mutations that can lead to recurrence if not removed together with the tumor.

  18. Modeling the Pro-inflammatory Tumor Microenvironment in Acute Lymphoblastic Leukemia Predicts a Breakdown of Hematopoietic-Mesenchymal Communication Networks

    Science.gov (United States)

    Enciso, Jennifer; Mayani, Hector; Mendoza, Luis; Pelayo, Rosana

    2016-01-01

    Lineage fate decisions of hematopoietic cells depend on intrinsic factors and extrinsic signals provided by the bone marrow microenvironment, where they reside. Abnormalities in composition and function of hematopoietic niches have been proposed as key contributors of acute lymphoblastic leukemia (ALL) progression. Our previous experimental findings strongly suggest that pro-inflammatory cues contribute to mesenchymal niche abnormalities that result in maintenance of ALL precursor cells at the expense of normal hematopoiesis. Here, we propose a molecular regulatory network interconnecting the major communication pathways between hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs) within the BM. Dynamical analysis of the network as a Boolean model reveals two stationary states that can be interpreted as the intercellular contact status. Furthermore, simulations describe the molecular patterns observed during experimental proliferation and activation. Importantly, our model predicts instability in the CXCR4/CXCL12 and VLA4/VCAM1 interactions following microenvironmental perturbation due by temporal signaling from Toll like receptors (TLRs) ligation. Therefore, aberrant expression of NF-κB induced by intrinsic or extrinsic factors may contribute to create a tumor microenvironment where a negative feedback loop inhibiting CXCR4/CXCL12 and VLA4/VCAM1 cellular communication axes allows for the maintenance of malignant cells. PMID:27594840

  19. Modeling the Pro-inflammatory Tumor Microenvironment in Acute Lymphoblastic Leukemia Predicts a Breakdown of Hematopoietic-Mesenchymal Communication Networks.

    Science.gov (United States)

    Enciso, Jennifer; Mayani, Hector; Mendoza, Luis; Pelayo, Rosana

    2016-01-01

    Lineage fate decisions of hematopoietic cells depend on intrinsic factors and extrinsic signals provided by the bone marrow microenvironment, where they reside. Abnormalities in composition and function of hematopoietic niches have been proposed as key contributors of acute lymphoblastic leukemia (ALL) progression. Our previous experimental findings strongly suggest that pro-inflammatory cues contribute to mesenchymal niche abnormalities that result in maintenance of ALL precursor cells at the expense of normal hematopoiesis. Here, we propose a molecular regulatory network interconnecting the major communication pathways between hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs) within the BM. Dynamical analysis of the network as a Boolean model reveals two stationary states that can be interpreted as the intercellular contact status. Furthermore, simulations describe the molecular patterns observed during experimental proliferation and activation. Importantly, our model predicts instability in the CXCR4/CXCL12 and VLA4/VCAM1 interactions following microenvironmental perturbation due by temporal signaling from Toll like receptors (TLRs) ligation. Therefore, aberrant expression of NF-κB induced by intrinsic or extrinsic factors may contribute to create a tumor microenvironment where a negative feedback loop inhibiting CXCR4/CXCL12 and VLA4/VCAM1 cellular communication axes allows for the maintenance of malignant cells.

  20. Modeling the pro-inflammatory tumor microenvironment in acute lymphoblastic leukemia predicts a breakdown of hematopoietic-mesenchymal communication networks

    Directory of Open Access Journals (Sweden)

    Jennifer Enciso

    2016-08-01

    Full Text Available Lineage fate decisions of hematopoietic cells depend on intrinsic factors and extrinsic signals provided by the bone marrow microenvironment, where they reside. Abnormalities in composition and function of hematopoietic niches have been proposed as key contributors of acute lymphoblastic leukemia (ALL progression. Our previous experimental findings strongly suggest that pro-inflammatory cues contribute to mesenchymal niche abnormalities that result in maintenance of ALL precursor cells at the expense of normal hematopoiesis. Here, we propose a molecular regulatory network interconnecting the major communication pathways between hematopoietic stem and progenitor cells (HSPCs and mesenchymal stromal cells (MSCs within the bone marrow. Dynamical analysis of the network as a Boolean model reveals two stationary states that can be interpreted as the intercellular contact status. Furthermore, simulations describe the molecular patterns observed during experimental proliferation and activation. Importantly, our model predicts instability in the CXCR4/CXCL12 and VLA4/VCAM1 interactions following microenvironmental perturbation due by temporal signaling from Toll like receptors (TLRs ligation. Therefore, aberrant expression of NF-κB induced by intrinsic or extrinsic factors may contribute to create a tumor microenvironment where a negative feedback loop inhibiting CXCR4/CXCL12 and VLA4/VCAM1 cellular communication axes allows for the maintenance of malignant cells.

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

    OpenAIRE

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

    1997-01-01

    The role of progestins in the pathogenesis of breast cancer in women remains controversial. To advance this discussion, we report the demonstration and localization of progestin-induced biosynthesis of growth hormone (GH) in canine mammary gland tissue. Nontumorous mammary tissues and tumors, both benign and malignant, were obtained from private household dogs. Immunoreactive GH was localized in mammary epithelial cells and correlated with the presence of GH mRNA. Local synthesis of GH was al...

  2. Intratumoral FoxP3 expression is associated with angiogenesis and prognosis in malignant canine mammary tumors.

    Science.gov (United States)

    Carvalho, Maria Isabel; Pires, Isabel; Prada, Justina; Gregório, Hugo; Lobo, Luis; Queiroga, Felisbina L

    2016-10-01

    The activity of regulatory T cells (Tregs) is closely associated with the expression of FoxP3 transcription factor. FoxP3 regulatory T cells (FoxP3Treg) have immunosuppressive properties and can work for prevention of harmful autoimmune responses, however can also interfere with beneficial anti-tumor immunity. In human breast cancer these cells play a crucial role in tumor progression. In canine mammary tumors (CMT) this topic is not well-documented. This study included 80 malignant CMT and studied, by immunohistochemistry, the intratumoral FoxP3 expression together with microvessel density (MVD), vascular endothelial growth factor (VEGF) and several clinicopathological characteristics. Abundant FoxP3Treg cells were associated with tumor necrosis (p=0.001), high mitotic grade (paggression in these tumors. The association of intratumoral FoxP3 expression with shorter OS in multivariate analysis suggests the usefulness of Treg cells as an independent prognostic marker. PMID:27496736

  3. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Storb, Rainer; Gyurkocza, Boglarka; Storer, Barry E;

    2013-01-01

    We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the pures...

  4. Evaluation of tumor markers carcinoembryonic antigen, cytokeratin 19 fragment and cancer-associated antigen 72-4 in neoplastic and non-neoplastic canine effusions differentiation

    OpenAIRE

    L.V Teixeira; T.A. Guerra; F.O. Conrado; S.R. Terra; D.G. Gerardi; González, F.H.D.

    2014-01-01

    The concentration of tumor markers in body fluids can be used for diagnosis and prognosis of patients. This study aimed to investigate the performance of tumor markers cytokeratin 19 fragment (CYFRA 21-1), cancer-associated antigen 72-4 (CA 72-4) and carcinoembryonic antigen (CEA) in the neoplastic and non-neoplastic canine effusions. In thirty-two neoplastic (n=16) and non-neoplastic (n=16) samples of canine thoracic or abdominal effusions, tumor markers were measured. Significant statistica...

  5. Correlation of tumor-infiltrating lymphocytes to histopathological features and molecular phenotypes in canine mammary carcinoma: A morphologic and immunohistochemical morphometric study

    OpenAIRE

    Kim, Jong-Hyuk; Chon, Seung-Ki; Im, Keum-Soon; Kim, Na-Hyun; Sur, Jung-Hyang

    2013-01-01

    Abundant lymphocyte infiltration is frequently found in canine malignant mammary tumors, but the pathological features and immunophenotypes associated with the infiltration remain to be elucidated. The aim of the present study was to evaluate the relationship between lymphocyte infiltration, histopathological features, and molecular phenotype in canine mammary carcinoma (MC). The study was done with archived formalin-fixed, paraffin-embedded samples (n = 47) by histologic and immunohistochemi...

  6. A novel role of hematopoietic CCL5 in promoting triple-negative mammary tumor progression by regulating generation of myeloid-derived suppressor cells

    Institute of Scientific and Technical Information of China (English)

    Yan Zhang; Dandan Lv; Ha-Jeong Kim; Robert A Kurt; Wen Bu; Yi Li; Xiaojing Ma

    2013-01-01

    CCL5 is a member of the CC chemokine family expressed in a wide array of immune and non-immune cells in response to stress signals.CCL5 expression correlates with advanced human breast cancer.However,its functional significance and mode of action have not been established.Here,we show that CCL5-deficient mice are resistant to highly aggressive,triple-negative mammary tumor growth.Hematopoietic CCL5 is dominant in this phenotype.The absence of hematopoietic CCL5 causes aberrant generation of CD11b+/Gr-1+,myeloid-derived suppressor cells (MDSCs) in the bone marrow in response to tumor growth by accumulating Ly6Chi and Ly6G+ MDSCs with impaired capacity to suppress cytotoxicity of CD8+ T cells.These properties of CCL5 are observed in both orthotopic and spontaneous mammary tumors.Antibody-mediated systemic blockade of CCL5 inhibits tumor progression and enhances the efficacy of therapeutic vaccination against non-immunogenic tumors.CCL5 also helps maintain the immunosuppressive capacity of human MDSCs.Our study uncovers a novel,chemokine-independent activity of the hematopoietically derived CCL5 that promotes mammary tumor progression via generating MDSCs in the bone marrow in cooperation with tumor-derived colony-stimulating factors.The study sheds considerable light on the interplay between the hematopoietic compartment and tumor niche.Because of the apparent dispensable nature of this molecule in normal physiology,CCL5 may represent an excellent therapeutic target in immunotherapy for breast cancer as well as a broad range of solid tumors that have significant amounts of MDSC infiltration.

  7. Failure-to-thrive syndrome associated with tumor formation by Madin-Darby canine kidney cells in newborn nude mice.

    Science.gov (United States)

    Brinster, Lauren R; Omeir, Romelda L; Foseh, Gideon S; Macauley, Juliete N; Snoy, Philip J; Beren, Joel J; Teferedegne, Belete; Peden, Keith; Lewis, Andrew M

    2013-08-01

    Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin-Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor-derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases. PMID:24209967

  8. Selenium Induces an Anti-tumor Effect Via Inhibiting Intratumoral Angiogenesis in a Mouse Model of Transplanted Canine Mammary Tumor Cells.

    Science.gov (United States)

    Li, Wenyu; Guo, Mengyao; Liu, Yuzhu; Mu, Weiwei; Deng, Ganzhen; Li, Chengye; Qiu, Changwei

    2016-06-01

    Selenium (Se) has been widely reported to possess anti-tumor effects. Angiogenesis is the formation of new blood vessels and is required to supply oxygen, nutrients, and growth factors for tumor growth, progression, and metastasis. To explore whether the anti-tumor effect of Se was associated with angiogenesis in vivo, we studied the effects of sodium selenite (Sel) and methylseleninic acid (MSA) on tumors induced by canine mammary tumor cells (CMT1211) in mice; cyclophosphamide (CTX) served as a positive control. The results showed that the Se content was significantly increased in the Sel and MSA groups. Se significantly inhibited the tumor weights and volumes. Large necrotic areas and scattered and abnormal small necrotic areas were observed in the Se treatment group. Immunofluorescence double staining showed a reduction in the microvessel density (MVD) and increment in the vessel maturation index (VMI) compared with the untreated control group. As expected, the protein and mRNA levels of the angiogenesis factors angiopoietin-2 (Ang-2), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) were decreased in the Se-treated tumors by IHC, as shown by western blotting and RT-QPCR. We also found that organic Se MSA provided stronger inhibition of tumor growth compared with inorganic sodium selenite (Sel). Altogether, our results indicated that Se exerted anti-tumor effects in vivo at least partially by inhibiting angiogenic factors. PMID:26507439

  9. High-Dose Chemotherapy with Autologous Hematopoietic Stem-Cell Rescue for Pediatric Brain Tumor Patients: A Single Institution Experience from UCLA

    OpenAIRE

    Panosyan, Eduard H.; IKEDA, ALAN K.; Chang, Vivian Y.; Laks, Dan R.; Charles L. Reeb; La Vette Bowles; Lasky, Joseph L.; Moore, Theodore B.

    2011-01-01

    Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR). Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999–2009). Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal ...

  10. Hematopoietic stem cell-derived adipocytes and fibroblastsin the tumor microenvironment

    Institute of Scientific and Technical Information of China (English)

    Ying Xiong; Lindsay T McDonald; Dayvia L Russell; Ryan R Kelly; Katie R Wilson; Meenal Mehrotra; Adam C Soloff; Amanda C LaRue

    2015-01-01

    The tumor microenvironment (TME) is complex andconstantly evolving. This is due, in part, to the crosstalkbetween tumor cells and the multiple cell types thatcomprise the TME, which results in a heterogeneouspopulation of tumor cells and TME cells. This reviewwill focus on two stromal cell types, the cancerassociatedadipocyte (CAA) and the cancer-associatedfibroblast (CAF). In the clinic, the presence of CAAsand CAFs in the TME translates to poor prognosis inmultiple tumor types. CAAs and CAFs have an activatedphenotype and produce growth factors, inflammatoryfactors, cytokines, chemokines, extracellular matrixcomponents, and proteases in an accelerated andaberrant fashion. Through this activated state, CAAs andCAFs remodel the TME, thereby driving all aspects oftumor progression, including tumor growth and survival,chemoresistance, tumor vascularization, tumor invasion,and tumor cell metastasis. Similarities in the tumorpromotingfunctions of CAAs and CAFs suggest that amultipronged therapeutic approach may be necessaryto achieve maximal impact on disease. While CAAsand CAFs are thought to arise from tissues adjacentto the tumor, multiple alternative origins for CAAs andCAFs have recently been identified. Recent studiesfrom our lab and others suggest that the hematopoieticstem cell, through the myeloid lineage, may serve asa progenitor for CAAs and CAFs. We hypothesize thatthe multiple origins of CAAs and CAFs may contributeto the heterogeneity seen in the TME. Thus, a betterunderstanding of the origin of CAAs and CAFs, howthis origin impacts their functions in the TME, and the temporal participation of uniquely originating TME cells may lead to novel or improved anti-tumor therapeutics.

  11. 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

    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...

  12. Multimodality functional imaging of spontaneous canine tumors using 64CU-ATSM and 18FDG PET/CT and dynamic contrast enhanced perfusion CT

    DEFF Research Database (Denmark)

    Hansen, Anders E; Kristensen, Annemarie T; Law, Ian;

    2012-01-01

    To compare the distribution and uptake of the hypoxia tracer (64)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) ((64)Cu-ATSM) PET/CT, FDG PET/CT and dynamic contrast enhanced perfusion CT (DCE-pCT) in spontaneous canine tumors. In addition (64)Cu-ATSM distribution over time was evaluated....

  13. A novel potent Fas agonist for selective depletion of tumor cells in hematopoietic transplants

    OpenAIRE

    Nahimana, A; AUBRY, D.; Lagopoulos, L; Greaney, P.; Attinger, A; Demotz, S; Dawson, K. M.; Schapira, M; Tschopp, J; Dupuis, M.; Duchosal, M A

    2011-01-01

    There remains a clear need for effective tumor cell purging in autologous stem cell transplantation (ASCT) where residual malignant cells within the autograft contribute to disease relapse. Here we propose the use of a novel Fas agonist with potent pro-apoptotic activity, termed MegaFasL, as an effective ex-vivo purging agent. MegaFasL selectively kills hematological cancer cells from lymphomas and leukemias and prevents tumor development at concentrations that do not reduce the functional ca...

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

    Directory of Open Access Journals (Sweden)

    Ali MRK

    2016-09-01

    Full Text Available Moustafa R K Ali,1 Ibrahim M Ibrahim,2,† Hala R Ali,2,3 Salah A Selim,2 Mostafa A El-Sayed1,4 1School of Chemistry and Biochemistry, Georgia Institute of Technology, and Laser Dynamics Laboratory, Atlanta, GA, USA; 2Department of Veterinary Medicine, Cairo University, Giza, Cairo, Egypt; 3Department of Bacteriology and Immunology, Animal Health Research Institute (AHRI, Dokki, Giza, Egypt; 4School of Chemistry, King Abdul Aziz University, Jeddah, Saudi Arabia †Ibrahim M Ibrahim passed away on August 23, 2015 Abstract: Plasmonic photothermal therapy (PPTT is a cancer therapy in which gold nanorods are injected at the site of a tumor before near-infrared light is transiently applied to the tumor causing localized cell death. Previously, PPTT studies have been carried out on xenograft mice models. Herein, we report a study showing the feasibility of PPTT as applied to natural tumors in the mammary glands of dogs and cats, which more realistically represent their human equivalents at the molecular level. We optimized a regime of three low PPTT doses at 2-week intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland tumors from seven animals. Histopathology, X-ray, blood profiles, and comprehensive examinations were used for both the diagnosis and the evaluation of tumor statuses before and after treatment. Histopathology results showed an obvious reduction in the cancer grade shortly after the first treatment and a complete regression after the third treatment. Blood tests showed no obvious change in liver and kidney functions. Similarly, X-ray diffraction showed no metastasis after 1 year of treatment. In conclusion, our study suggests the feasibility of applying the gold nanorods-PPTT on natural tumors in dogs and cats without any relapse or toxicity effects after 1 year of treatment. Keywords: gold nanorods, natural mammary tumors, plasmonic photothermal therapy, canine, feline

  15. Use of an image-guided robotic radiosurgery system for the treatment of canine nonlymphomatous nasal tumors.

    Science.gov (United States)

    Glasser, Seth A; Charney, Sarah; Dervisis, Nikolaos G; Witten, Matthew R; Ettinger, Susan; Berg, Jason; Joseph, Richard

    2014-01-01

    An image-guided robotic stereotactic radiosurgery (SRS) system can be used to deliver curative-intent radiation in either single fraction or hypofractionated doses. Medical records for 19 dogs with nonlymphomatous nasal tumors treated with hypofractionated image-guided robotic stereotactic body radiotherapy (SBRT), either with or without adjunctive treatment, were retrospectively analyzed for survival and prognostic factors. Median survival time (MST) was evaluated using Kaplan-Meier survival curves. Age, breed, tumor type, stage, tumor size, prescribed radiation dose, and heterogeneity index were analyzed for prognostic significance. Dogs were treated with three consecutive-day, 8-12 gray (Gy) fractions of image-guided robotic SBRT. Overall MST was 399 days. No significant prognostic factors were identified. Acute side effects were rare and mild. Late side effects included one dog with an oronasal fistula and six dogs with seizures. In three of six dogs, seizures were a presenting complaint prior to SBRT. The cause of seizures in the remaining three dogs could not be definitively determined due to lack of follow-up computed tomography (CT) imaging. The seizures could have been related to either progression of disease or late radiation effect. Results indicate that image-guided robotic SBRT, either with or without adjunctive therapy, for canine nonlymphomatous nasal tumors provides comparable survival times (STs) to daily fractionated megavoltage radiation with fewer required fractions and fewer acute side effects. PMID:24446402

  16. Cloning of aminopeptidase Npromoter and its activity in hematopoietic cell and different tumor cell lines

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Aminopeptidase N (APN) promoter region was cloned and sequenced from peripheral blood mononuclear cells. The recombinant reporter construct containing the promoter and luciferase gene, designated pXP1-APNLuc, was introduced into myeloblastic cell line, T lymphocyte cell line and various tumor cell lines. Luciferase assay showed that APN upstream promoter is myeloid-specific for high expression in myeloblastic cell line and much lower expres sion in T lymphocyte cell line. The promoter activity was relatively high in lung adenoma cell line compared with other tumor cell lines including hepatoma cell line, tong cancer cell line and esophageal cancer cell line in which the promoter activity significantly diminished or was almost undetectable. The characteristics of APN promoter may pro vide a new strategy for specific myeloprotection while tumor patients are being treated with chemotherapy and/or radio therapy.

  17. Establishment of a canine mammary gland tumor cell line and characterization of its miRNA expression

    Science.gov (United States)

    Sunden, Yuji; Sugiyama, Akihiko; Azuma, Kazuo; Murahata, Yusuke; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Okamoto, Yoshiharu

    2016-01-01

    Canine mammary gland tumors (CMGTs), which are the most common neoplasms in sexually intact female dogs, have been suggested as a model for studying human breast cancer because of several similarities, including relative age of onset, risk factors, incidence, histological and molecular features, biological behavior, metastatic pattern, and responses to therapy. In the present study, we established a new cell line, the SNP cell line, from a CMGT. A tumor formed in each NOD.CB17-Prkdcscid/J mouse at the site of subcutaneous SNP cell injection. SNP cells are characterized by proliferation in a tubulopapillary pattern and are vimentin positive. Moreover, we examined miRNA expression in the cultured cells and found that the expression values of miRNA-143 and miRNA-138a showed the greatest increase and decrease, respectively, of all miRNAs observed, indicating that these miRNAs might play a significant role in the malignancy of SNP cells. Overall, the results of this study indicate that SNP cells might serve as a model for future genetic analysis and clinical treatments of human breast tumors. PMID:26726024

  18. Correlation of tumor-infiltrating lymphocytes to histopathological features and molecular phenotypes in canine mammary carcinoma: A morphologic and immunohistochemical morphometric study.

    Science.gov (United States)

    Kim, Jong-Hyuk; Chon, Seung-Ki; Im, Keum-Soon; Kim, Na-Hyun; Sur, Jung-Hyang

    2013-04-01

    Abundant lymphocyte infiltration is frequently found in canine malignant mammary tumors, but the pathological features and immunophenotypes associated with the infiltration remain to be elucidated. The aim of the present study was to evaluate the relationship between lymphocyte infiltration, histopathological features, and molecular phenotype in canine mammary carcinoma (MC). The study was done with archived formalin-fixed, paraffin-embedded samples (n = 47) by histologic and immunohistochemical methods. The degree of lymphocyte infiltration was evaluated by morphologic analysis, and the T- and B-cell populations as well as the T/B-cell ratio were evaluated by morphometric analysis; results were compared with the histologic features and molecular phenotypes. The degree of lymphocyte infiltration was significantly higher in MCs with lymphatic invasion than in those without lymphatic invasion (P aggressive histologic features, lymphocytes may be important for tumor aggressiveness and greater malignant behavior in the tumor microenvironment. PMID:24082407

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

    Science.gov (United States)

    Guil-Luna, S; Stenvang, J; Brünner, N; Sánchez-Céspedes, R; Millán, Y; Gómez-Laguna, J; de las Mulas, J Martín

    2014-09-01

    Cloning and sequencing of the progesterone receptor gene in dogs have revealed 2 isoforms, A and B, transcribed from a single gene. Distribution of isoforms A and B in canine mammary lesions has hitherto been investigated only by Western blot analysis. This study analyzed progesterone receptor and its isoforms in formalin-fixed, paraffin-embedded tissue samples from canine mammary lesions (4 dysplasias, 10 benign tumors, and 46 carcinomas) using 1-step SYBR Green quantitative real-time polymerase chain reaction (RT-qPCR). Progesterone receptor was expressed in 75% of dysplasias, all benign tumors, and 59% of carcinomas. Carcinomas, and particularly simple epithelial-type carcinomas, displayed the lowest levels of expression. A high rate of agreement was recorded between RT-qPCR and immunohistochemical labeling. Isoforms A and B were successfully amplified, with correlation coefficients of 0.99 and amplification efficiencies close to 2, and were expressed in all lesion types analyzed. Predominance of A over B expression was observed in carcinomas and complex adenomas. Low-grade tumors exhibited higher progesterone receptor messenger RNA (mRNA) levels, but no difference was observed in the expression of isoform A versus B. Analysis of progesterone receptor mRNA isoforms by RT-qPCR was successful in routinely formalin-fixed, paraffin-embedded tissue samples and enabled the distribution of isoforms A and B to be identified for the first time in dysplasias, benign tumors, and malignant tumors of the canine mammary gland. These findings will facilitate future research into the role of progesterone receptor isoforms in the progression of canine mammary tumors. PMID:24249219

  20. Canine distemper virus induces apoptosis in cervical tumor derived cell lines

    Directory of Open Access Journals (Sweden)

    Rajão Daniela S

    2011-06-01

    Full Text Available Abstract Apoptosis can be induced or inhibited by viral proteins, it can form part of the host defense against virus infection, or it can be a mechanism for viral spread to neighboring cells. Canine distemper virus (CDV induces apoptotic cells in lymphoid tissues and in the cerebellum of dogs naturally infected. CDV also produces a cytopathologic effect, leading to apoptosis in Vero cells in tissue culture. We tested canine distemper virus, a member of the Paramyxoviridae family, for the ability to trigger apoptosis in HeLa cells, derived from cervical cancer cells resistant to apoptosis. To study the effect of CDV infection in HeLa cells, we examined apoptotic markers 24 h post infection (pi, by flow cytometry assay for DNA fragmentation, real-time PCR assay for caspase-3 and caspase-8 mRNA expression, and by caspase-3 and -8 immunocytochemistry. Flow cytometry showed that DNA fragmentation was induced in HeLa cells infected by CDV, and immunocytochemistry revealed a significant increase in the levels of the cleaved active form of caspase-3 protein, but did not show any difference in expression of caspase-8, indicating an intrinsic apoptotic pathway. Confirming this observation, expression of caspase-3 mRNA was higher in CDV infected HeLa cells than control cells; however, there was no statistically significant change in caspase-8 mRNA expression profile. Our data suggest that canine distemper virus induced apoptosis in HeLa cells, triggering apoptosis by the intrinsic pathway, with no participation of the initiator caspase -8 from the extrinsic pathway. In conclusion, the cellular stress caused by CDV infection of HeLa cells, leading to apoptosis, can be used as a tool in future research for cervical cancer treatment and control.

  1. A comparison of oral and intravenous pimonidazole in canine tumors using intravenous CCI-103F as a control hypoxia marker

    International Nuclear Information System (INIS)

    Purpose: Pimonidazole HCl is widely used in immunohistochemical analyses of hypoxia in normal and malignant tissues. The present study investigates oral administration as a means of minimizing invasiveness. Methods and Materials: Twelve dogs with confirmed malignancy received 0.5 g/m2 of pimonidazole HCl: 6 by mouth and 6 by i.v. infusion. All dogs received i.v. CCI-103F as a control. Plasma levels of pimonidazole, pimonidazole N-oxide, and CCI-103F were measured. Tumor biopsies were formalin fixed, paraffin embedded, sectioned, immunostained, and analyzed for pimonidazole and CCI-103F binding. pH dependence for pimonidazole and CCI-103F binding was studied in vitro. Results: Pimonidazole and CCI-103F binding in carcinomas and sarcomas was strongly correlated for both oral and i.v. pimonidazole HCl (r 2 = 0.97). On average, the extent of pimonidazole binding exceeded that for CCI-103F by a factor of approximately 1.2, with the factor ranging from 1.0 to 1.65. Binding of both markers was pH dependent, but pimonidazole binding was greater at all values of pH. Conclusions: Oral pimonidazole HCl is effective as a hypoxia marker in spontaneously arising canine tumors. Selective cellular uptake and concomitant higher levels of binding in regions of hypoxia at the high end of pH gradients might account for the greater extent of pimonidazole binding

  2. Novel frameshift mutation in the p16/INK4A tumor suppressor gene in canine breast cancer alters expression from the p16/INK4A/p14ARF locus.

    Science.gov (United States)

    Lutful Kabir, Farruk M; Agarwal, Payal; Deinnocentes, Patricia; Zaman, Jishan; Bird, Allison Church; Bird, R Curtis

    2013-01-01

    The INK4 family of cyclin-dependent kinase inhibitors (CKI) encode important cell cycle regulators that tightly control cell cycle during G1 to S phase. These related genes are considered tumor suppressors as loss of function contributes to the malignant phenotype. Expression of CKIs p16, p14ARF, or p15 were defective in six different canine mammary tumor (CMT) cell lines compared to normal thoracic canine fibroblasts. This suggests CKI defects are frequently responsible for neoplastic transformation in canine mammary carcinomas. p16 and p14ARF are two alternatively spliced products derived from the canine p16/INK4A/p14ARF gene locus. Despite omissions in the published p16 transcript and canine genome and the presence of GC-rich repeats, we determined the complete coding sequence of canine p16 revealing a deletion and frameshift mutation in p16 exon 1α in CMT28 cells. In addition, we determined canine p14ARF mRNA and protein sequences. Mapping of these mutations uncovered important aspects of p16 and p14ARF expression and defects in CMT28 cells shifting the p16 reading frame into p14ARF making a fusion protein that was predicted to be truncated, unstable and devoid of structural and functional integrity. This data describes an important neoplastic mechanism in the p16/INK4A/p14ARF locus in a spontaneous canine model of breast cancer.

  3. Spontaneous canine transmissible venereal tumor: cell morphology and influence on P-glycoprotein expression

    OpenAIRE

    GASPAR, Luis Fernando Jantzen; FERREIRA, Isabelle; COLODEL, Marcia MOLETA

    2010-01-01

    The present study aimed to determine P-glycoprotein expression according to TVT cell morphology in 42 dogs with confirmed TVT, classified into lymphocytoid, plasmocytoid, and mixed. The chemotherapy efficiency was investigated along with its relation to P-glycoprotein expression in tumoral cells, evaluated by immunocytochemistry, considering positive tumors more than 10% stained. Among the samples collected, 50.00% possessed plasmocytoid morphology, 18.63% lymphocytoid, and 31.37% mixed. The ...

  4. Cytological diagnosis of a metastatic canine mammary tumor in pleural effusion

    OpenAIRE

    Cassali G.D.; Gärtner F.; Vieira da Silva M.J.; Schmitt F.C.

    1999-01-01

    Descrevem-se os achados citomorfológicos de um tumor maligno de mama em uma cadela Poodle de sete anos de idade, o qual foi observado inicialmente pelo exame citológico do derrame pleural. Comparam-se os aspectos citológicos do derrame pleural e punção aspirativa com agulha fina do tumor com aqueles descritos para o câncer de mama na espécie humana.

  5. Tumor induction following intraoperative radiotherapy: Late results of the National Cancer Institute canine trials

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, M.; Duray, P.; DeLuca, A.; Anderson, W.; Sindelar, W.; Kinsella, T. (Fox Chase Cancer Center, Philadelphia, PA (USA))

    1990-09-01

    Intraoperative radiotherapy has been employed in human cancer research for over a decade. Since 1979, trials to assess the acute and late toxicity of IORT have been carried out at the National Cancer Institute in an adult dog model in an attempt to establish dose tolerance guidelines for a variety of organs. Of the 170 animals entered on 12 studies with a minimum follow-up of 2 years, 148 dogs received IORT; 22 control animals received only surgery. Animals were sacrificed at designated intervals following IORT, usually at 1, 6, 12, 24, and 60 month intervals. 102 of 148 irradiated dogs were sacrificed less than 24 months; 46 dogs were followed greater than or equal to 24 months after IORT. To date, 34 of the 46 animals have been sacrificed; the 12 remaining animals are to be followed to 5 years. These 12 animals have minimum follow-up of 30 months. In the irradiated group followed for greater than or equal to 24 months, 10 tumors have arisen in 9 animals. One animal developed an incidental spontaneous breast carcinoma outside the IORT port, discovered only at scheduled post-mortem exam. The remaining nine tumors arose within IORT ports. Two tumors were benign neural tumors--a neuroma and a neurofibroma. One animal had a collision tumor comprised of grade I chondrosarcoma adjacent to grade III osteosarcoma arising in lumbar vertebrae. Two other grade III osteosarcomas, one grade III fibrosarcoma, and one grade III malignant fibrous histiocytoma arose in retroperitoneal/paravertebral sites. An embryonal rhabdomyosarcoma (sarcoma botryoides) arose within the irradiated urinary bladder of one animal. No sham irradiated controls nor IORT animals sacrificed less than 24 months have developed any spontaneous or radiation-induced tumors. The time range of diagnoses of tumors was 24-58 months. The IORT dose range associated with tumor development was 20-35 Gy.

  6. The maspin expression in canine mammary tumors: an immunohistochemical and molecular study A expressão do maspin nos tumores mamários caninos: um estudo imuno-histoquímico e molecular

    Directory of Open Access Journals (Sweden)

    Debora A.P.C. Zuccari

    2009-02-01

    Full Text Available The serpin maspin, a tumor suppressor in breast cancer was described as an inhibitor of cell migration and inducer of cell adhesion between the basement membrane and extracellular matrix resulting in inhibition of tumor metastasis. In contrast, overexpression of maspin is correlated with poor prognosis in other types of cancer. Little is known about expression, regulation and function of maspin in canine mammary tumors. It was demonstrated in this study, a loss of maspin expression in malignant canine mammary cells compared with a pool of normal canine mammary tissue, analyzed by quantitative real-time PCR; weak maspin expression in malignant canine mammary tumors were observed by immunohistochemistry. It was also demonstrated that a correlation with nuclear maspin expression and a good prognosis. It is suggested that maspin could be used as a prognostic marker in canine mammary neoplasia.O serpin maspin, um supressor tumoral no câncer de mama foi descrito como inibidor de migração celular e indutor de adesão celular entre a membrana basal e a matriz extracelular resultando na inibição da metástase tumoral. Por outro lado, a alta expressão do maspin está relacionada com um mau prognóstico em outros tipos de câncer. Pouco se sabe sobre a expressão, regulação e função do maspin nos tumores mamários caninos. Neste estudo, foi demonstrada uma perda da expressão de maspin nas células mamárias malignas de cães quando comparadas com um pool de tecido mamário normal de cães, analisado por PCR quantitativa em tempo real. Houve uma expressão fraca maspin em preparações de tumores mamários malignos observadas por imuno-histoquímica. Também foi verificado que a expressão nuclear do maspin em tumores mamários caninos está relacionada a um bom prognóstico. Assim, o maspin pode ser utilizado como um marcador prognóstico nas neoplasias mamárias em cães.

  7. Alternativas Terapéuticas en las neoplasias vesicales caninas Therapeutic options in canine bladder tumors

    OpenAIRE

    R.L. Rovere; A. ALCOBA

    2002-01-01

    Las neoplasias vesicales en caninos representan menos del 1% de los tumores presentes en esta especie. El tratamiento quirúrgico se indica en tumores benignos y como complemento de la quimioterapia y radioterapia. Para la quimioterapia se emplean más frecuentemente la doxorrubicina, el 5-fluorouracilo, la ciclofosfamida, la vincristina y cisplatino. La asociación de la doxorrubicina-ciclofosfamida por vía sistémica en asociación con el cisplatino intravesical, sería un tratamiento recomendabl...

  8. Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior.

    Science.gov (United States)

    Kiupel, M; Webster, J D; Bailey, K L; Best, S; DeLay, J; Detrisac, C J; Fitzgerald, S D; Gamble, D; Ginn, P E; Goldschmidt, M H; Hendrick, M J; Howerth, E W; Janovitz, E B; Langohr, I; Lenz, S D; Lipscomb, T P; Miller, M A; Misdorp, W; Moroff, S; Mullaney, T P; Neyens, I; O'Toole, D; Ramos-Vara, J; Scase, T J; Schulman, F Y; Sledge, D; Smedley, R C; Smith, K; W Snyder, P; Southorn, E; Stedman, N L; Steficek, B A; Stromberg, P C; Valli, V E; Weisbrode, S E; Yager, J; Heller, J; Miller, R

    2011-01-01

    Currently, prognostic and therapeutic determinations for canine cutaneous mast cell tumors (MCTs) are primarily based on histologic grade. However, the use of different grading systems by veterinary pathologists and institutional modifications make the prognostic value of histologic grading highly questionable. To evaluate the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system, 95 cutaneous MCTs from 95 dogs were graded in a blinded study by 28 veterinary pathologists from 16 institutions. Concordance among veterinary pathologists was 75% for the diagnosis of grade 3 MCTs and less than 64% for the diagnosis of grade 1 and 2 MCTs. To improve concordance among pathologists and to provide better prognostic significance, a 2-tier histologic grading system was devised. The diagnosis of high-grade MCTs is based on the presence of any one of the following criteria: at least 7 mitotic figures in 10 high-power fields (hpf); at least 3 multinucleated (3 or more nuclei) cells in 10 hpf; at least 3 bizarre nuclei in 10 hpf; karyomegaly (ie, nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold). Fields with the highest mitotic activity or with the highest degree of anisokaryosis were selected to assess the different parameters. According to the novel grading system, high-grade MCTs were significantly associated with shorter time to metastasis or new tumor development, and with shorter survival time. The median survival time was less than 4 months for high-grade MCTs but more than 2 years for low-grade MCTs.

  9. Altered microRNA Expression Profiles and Regulation of INK4A/CDKN2A Tumor Suppressor Genes in Canine Breast Cancer Models.

    Science.gov (United States)

    Lutful Kabir, Farruk Mohammad; DeInnocentes, Patricia; Bird, Richard Curtis

    2015-12-01

    microRNA (miRNA) expression profiling of cancer versus normal cells may reveal the characteristic regulatory features that can be correlated to altered gene expression in both human and animal models of cancers. In this study, the comprehensive expression profiles of the 277 highly characterized miRNAs from the canine genome were evaluated in spontaneous canine mammary tumor (CMT) models harboring defects in a group of cell cycle regulatory and potent tumor suppressor genes of INK4/CDKN2 family including p16/INK4A, p14ARF, and p15/INK4B. A large number of differentially expressed miRNAs were identified in three CMT cell lines to potentially target oncogenes, tumor suppressor genes and cancer biomarkers. A group of the altered miRNAs were identified by miRNA target prediction tools for regulation of the INK4/CDKN2 family tumor suppressor genes. miRNA-141 was experimentally validated for INK4A 3'-UTR target binding in the CMT cell lines providing an essential mechanism for the post-transcriptional regulation of the INK4A tumor suppressor gene in CMT models. A well-recognized group of miRNAs including miR-21, miR-155, miR-9, miR-34a, miR-143/145, and miR-31 were found to be altered in both CMTs and human breast cancer. These altered miRNAs might serve as potential targets for advancing the development of future therapeutic reagents. These findings further strengthen the validity and use of canine breast cancers as appropriate models for the study of human breast cancers. PMID:26095675

  10. Canine mammary tumors: a review and consensus of standard guidelines on epithelial and myoepithelial phenotype markers, HER2, and hormone receptor assessment using immunohistochemistry.

    Science.gov (United States)

    Peña, L; Gama, A; Goldschmidt, M H; Abadie, J; Benazzi, C; Castagnaro, M; Díez, L; Gärtner, F; Hellmén, E; Kiupel, M; Millán, Y; Miller, M A; Nguyen, F; Poli, A; Sarli, G; Zappulli, V; de las Mulas, J Martín

    2014-01-01

    Although there have been several studies on the use of immunohistochemical biomarkers of canine mammary tumors (CMTs), the results are difficult to compare. This article provides guidelines on the most useful immunohistochemical markers to standardize their use and understand how outcomes are measured, thus ensuring reproducibility of results. We have reviewed the biomarkers of canine mammary epithelial and myoepithelial cells and identified those biomarkers that are most useful and those biomarkers for invasion and lymph node micrometastatic disease. A 10% threshold for positive reaction for most of these markers is recommended. Guidelines on immunolabeling for HER2, estrogen receptors (ERs), and progesterone receptors (PRs) are provided along with the specific recommendations for interpretation of the results for each of these biomarkers in CMTs. Only 3+ HER2-positive tumors should be considered positive, as found in human breast cancer. The lack of any known response to adjuvant endocrine therapy of ER- and PR-positive CMTs prevents the use of the biological positive/negative threshold used in human breast cancer. Immunohistochemistry results of ER and PR in CMTs should be reported as the sum of the percentage of positive cells and the intensity of immunolabeling (Allred score). Incorporation of these recommendations in future studies, either prospective or retrospective, will provide a mechanism for the direct comparison of studies and will help to determine whether these biomarkers have prognostic significance. Finally, these biomarkers may ascertain the most appropriate treatment(s) for canine malignant mammary neoplasms. PMID:24227007

  11. High-dose chemotherapy with autologous hematopoietic stem-cell rescue for pediatric brain tumor patients: a single institution experience from UCLA.

    Science.gov (United States)

    Panosyan, Eduard H; Ikeda, Alan K; Chang, Vivian Y; Laks, Dan R; Reeb, Charles L; Bowles, La Vette; Lasky, Joseph L; Moore, Theodore B

    2011-01-01

    Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR). Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999-2009). Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal tumors, and a pineoblastoma), 3 glial/mixed, and 3 germ cell tumors. Eight patients had initial gross-total and seven subtotal resections. HDCT mostly consisted of carboplatin and/or thiotepa ± etoposide (n = 16). Nine patients underwent a single AHSCR and nine ≥3 tandems. Three-year progression-free and overall survival probabilities were 60.5% ± 16 and 69.3% ± 11.5. Ten patients with pre-AHSCR complete remissions were alive/disease-free, whereas 5 of 8 with measurable disease were deceased (median followup: 2.3 yrs). Nine of 13 survivors avoided radiation. Single AHSCR regimens had greater toxicity than ≥3 AHSCR (P < .01). Conclusion. HDCT-AHSCR has a definitive, though limited role for selected pediatric brain tumors with poor prognosis and pretransplant complete/partial remissions. PMID:21559259

  12. High-Dose Chemotherapy with Autologous Hematopoietic Stem-Cell Rescue for Pediatric Brain Tumor Patients: A Single Institution Experience from UCLA

    Directory of Open Access Journals (Sweden)

    Eduard H. Panosyan

    2011-01-01

    Full Text Available Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR. Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999–2009. Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal tumors, and a pineoblastoma, 3 glial/mixed, and 3 germ cell tumors. Eight patients had initial gross-total and seven subtotal resections. HDCT mostly consisted of carboplatin and/or thiotepa ± etoposide (n=16. Nine patients underwent a single AHSCR and nine ≥3 tandems. Three-year progression-free and overall survival probabilities were 60.5% ± 16 and 69.3% ± 11.5. Ten patients with pre-AHSCR complete remissions were alive/disease-free, whereas 5 of 8 with measurable disease were deceased (median followup: 2.3 yrs. Nine of 13 survivors avoided radiation. Single AHSCR regimens had greater toxicity than ≥3 AHSCR (P<.01. Conclusion. HDCT-AHSCR has a definitive, though limited role for selected pediatric brain tumors with poor prognosis and pretransplant complete/partial remissions.

  13. Quantification of morphology of canine circumanal gland tumors: a fractal based study.

    Science.gov (United States)

    Šoštarić-Zuckermann, I C; Severin, K; Huzak, M; Hohšteter, M; Gudan Kurilj, A; Artuković, B; Džaja, A; Grabarević, Ž

    2016-01-01

    Circumanal gland tumors are very common neoplasms of dogs. Their classification relies on microscopic examination and is further supported by a few immunohistochemical markers that help indicate their prognosis. However, new additional tests would be highly useful. The purpose of this study was to develop such a test using fractal analysis which is increasingly being applied in science, especially in the field of biomedicine. A total of 53 circumanal gland tumors were chosen from our department archives. After a precise histological classification according to the World Health Organization classification, the number of de novo classified samples was as follows: 15 adenomas, 11 epitheliomas, 21 well differentiated carcinomas, 6 poorly differentiated carcinomas. Ten samples of normal circumanal gland were also included as control. All samples were immunohistochemicaly stained with vimentin. All immunohistochemical reactions were photographed at two different magnifications -100X and 400X and converted to 1 bit in black and white (bitmap) images thus enhancing the positive vimentin reactions. These images were used for the assessment of fractal dimension applying the box counting method and computer software Fractalyse. To determine the significance of results, conventional statistics were performed using Statistica software. The overall vimentin stain score was significantly higher in epitheliomas and carcinomas than in normal circumanal glands (CG) or adenomas. Mean values of fractal dimension estimated at magnification 100X and 400X were as follows: normal CG 1.318 and 1.372, CG adenomas 1.384 and 1.408, CG epitheliomas 1.547 and 1.597, CG well differentiated carcinomas 1.569 and 1.607, CG poorly differentiated carcinomas 1.679 and 1.723. Significant differences (at level of 5%) of these values were observed between individual groups of CG adenomas or normal CG, and epitheliomas or carcinomas. The above results indicate vimentin immunohistochemistry staining and

  14. Evaluation of tumor motion effect in canine model for diagnostic and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sangkeun; Nam, Taewon; Kim, Kyeongmin [Molecular Imaging Research Center, Seoul (Korea, Republic of); Park, Seungwoo; Han, Suchul; Ji, Younghoon [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Park, Nohwon; Eom, Kidong [Konkuk Univ., Seoul (Korea, Republic of)

    2013-05-15

    The internal organs move up to 35mm maximum and it provides information and uncertainty that has been distorted in the diagnosis and treatment. Previous most studies for the effect of respiration have been performed with external monitoring systems but it cannot represent internal organ motion such as liver, pancreas, and lung. Positron emission tomography (PET) is more influenced by motion than computed tomography (CT) and magnetic resonance imaging (MRI) since measurement time for image acquisition is longer than CT and MRI. Thus, count of tumor is to be underestimated and region of tumor is to be overestimated. The first aim of this study was developing the artificial pulmonary nodule which can be performed non-invasive transplant into thorax of dogs and second is to assess the effect of respiratory motion on PET image with evaluating the applicability of the artificial model using dogs for diagnosis and treatment. The developed artificial pulmonary nodule showed reproducibility and motion effect as respiratory cycle and it was verified in PET images. Radiation dose estimated was not changed and was reduced slightly of 10 rpm and 15 rpm, respectively, in both of glass dosimeter and ion chamber. The developed artificial pulmonary nodule will be useful tool for evaluating respiratory motion and better research performance for diagnosis and treatment will be expected with performing simulated experiment using the nodule conducted in this study.

  15. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

    Directory of Open Access Journals (Sweden)

    Abadie Jerome

    2011-05-01

    Full Text Available Abstract Background Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology. Methods Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed. Results Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis. Conclusions The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model

  16. Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior

    International Nuclear Information System (INIS)

    Histiocytic malignancies in both humans and dogs are rare and poorly understood. While canine histiocytic sarcoma (HS) is uncommon in the general domestic dog population, there is a strikingly high incidence in a subset of breeds, suggesting heritable predisposition. Molecular cytogenetic profiling of canine HS in these breeds would serve to reveal recurrent DNA copy number aberrations (CNAs) that are breed and/or tumor associated, as well as defining those shared with human HS. This process would identify evolutionarily conserved cytogenetic changes to highlight regions of particular importance to HS biology. Using genome wide array comparative genomic hybridization we assessed CNAs in 104 spontaneously occurring HS from two breeds of dog exhibiting a particularly elevated incidence of this tumor, the Bernese Mountain Dog and Flat-Coated Retriever. Recurrent CNAs were evaluated further by multicolor fluorescence in situ hybridization and loss of heterozygosity analyses. Statistical analyses were performed to identify CNAs associated with tumor location and breed. Almost all recurrent CNAs identified in this study were shared between the two breeds, suggesting that they are associated more with the cancer phenotype than with breed. A subset of recurrent genomic imbalances suggested involvement of known cancer associated genes in HS pathogenesis, including deletions of the tumor suppressor genes CDKN2A/B, RB1 and PTEN. A small number of aberrations were unique to each breed, implying that they may contribute to the major differences in tumor location evident in these two breeds. The most highly recurrent canine CNAs revealed in this study are evolutionarily conserved with those reported in human histiocytic proliferations, suggesting that human and dog HS share a conserved pathogenesis. The breed associated clinical features and DNA copy number aberrations exhibited by canine HS offer a valuable model for the human counterpart, providing additional evidence towards

  17. Evaluation of tumor markers carcinoembryonic antigen, cytokeratin 19 fragment and cancer-associated antigen 72-4 in neoplastic and non-neoplastic canine effusions differentiation

    Directory of Open Access Journals (Sweden)

    L.V. Teixeira

    2014-10-01

    Full Text Available The concentration of tumor markers in body fluids can be used for diagnosis and prognosis of patients. This study aimed to investigate the performance of tumor markers cytokeratin 19 fragment (CYFRA 21-1, cancer-associated antigen 72-4 (CA 72-4 and carcinoembryonic antigen (CEA in the neoplastic and non-neoplastic canine effusions. In thirty-two neoplastic (n=16 and non-neoplastic (n=16 samples of canine thoracic or abdominal effusions, tumor markers were measured. Significant statistical difference was found only for the CYFRA 21-1 marker. The levels were significantly higher for the neoplastic group. The lack of significance between groups for markers CA 72-4 and CEA can be explained by the presence of other diseases in the non-neoplastic group, causing elevated levels of these markers. This study concludes that CYFRA 21-1 performed well, showing good sensitivity, specificity and accuracy in the diagnosis of neoplastic effusions in dogs. However, further investigations are necessary in patients with malignancy as those with benign effusions.

  18. Canine Distemper

    Science.gov (United States)

    Although this brochure provides basic information about canine distemper, your veterinarian is always your best source of ... Consult your veterinarian for more information about canine distemper and its prevention. And Now A Note On ...

  19. A Comparison of Fresh Frozen vs. Formalin-Fixed, Paraffin-Embedded Specimens of Canine Mammary Tumors via Branched-DNA Assay

    Directory of Open Access Journals (Sweden)

    Florenza Lüder Ripoli

    2016-05-01

    Full Text Available Mammary neoplasms are the tumors most affecting female dogs and women. Formalin-fixed, paraffin-embedded (FFPE tissues are an invaluable source of archived biological material. Fresh frozen (FF tissue is considered ideal for gene expression analysis. However, strategies based on FFPE material offer several advantages. Branched-DNA assays permit a reliable and fast workflow when analyzing gene expression. The aim of this study was to assess the comparability of the branched-DNA assay when analyzing certain gene expression patterns between FF and FFPE samples in canine mammary tumors. RNA was isolated from 109 FFPE samples and from 93 FF samples of different canine mammary tissues. Sixteen (16 target genes (Tp53; Myc; HMGA1; Pik3ca; Mcl1; MAPK3; FOXO3; PTEN; GATA4; PFDN5; HMGB1; MAPK1; BRCA2; BRCA1; HMGA2; and Her2 were analyzed via branched-DNA assay (b-DNA. ACTB, GAPDH, and HPRT1 were used as data normalizers. Overall, the relative gene expression of the two different origins of samples showed an agreement of 63%. Still, care should be taken, as FFPE specimens showed lower expression of the analyzed targets when compared to FF samples. The fact that the gene expression in FFPE proved to be lower than in FF specimens is likely to have been caused by the effect of storage time. ACTB had the best performance as a data normalizer.

  20. A Comparison of Fresh Frozen vs. Formalin-Fixed, Paraffin-Embedded Specimens of Canine Mammary Tumors via Branched-DNA Assay.

    Science.gov (United States)

    Lüder Ripoli, Florenza; Mohr, Annika; Conradine Hammer, Susanne; Willenbrock, Saskia; Hewicker-Trautwein, Marion; Hennecke, Silvia; Murua Escobar, Hugo; Nolte, Ingo

    2016-01-01

    Mammary neoplasms are the tumors most affecting female dogs and women. Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable source of archived biological material. Fresh frozen (FF) tissue is considered ideal for gene expression analysis. However, strategies based on FFPE material offer several advantages. Branched-DNA assays permit a reliable and fast workflow when analyzing gene expression. The aim of this study was to assess the comparability of the branched-DNA assay when analyzing certain gene expression patterns between FF and FFPE samples in canine mammary tumors. RNA was isolated from 109 FFPE samples and from 93 FF samples of different canine mammary tissues. Sixteen (16) target genes (Tp53; Myc; HMGA1; Pik3ca; Mcl1; MAPK3; FOXO3; PTEN; GATA4; PFDN5; HMGB1; MAPK1; BRCA2; BRCA1; HMGA2; and Her2) were analyzed via branched-DNA assay (b-DNA). ACTB, GAPDH, and HPRT1 were used as data normalizers. Overall, the relative gene expression of the two different origins of samples showed an agreement of 63%. Still, care should be taken, as FFPE specimens showed lower expression of the analyzed targets when compared to FF samples. The fact that the gene expression in FFPE proved to be lower than in FF specimens is likely to have been caused by the effect of storage time. ACTB had the best performance as a data normalizer. PMID:27187374

  1. Hematopoietic System

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    2011370 The efficacy and safety of second allogeneic hematopoietic stem cell transplantation for post-transplant hematologic malignancies relapse. CHEN Yuhong(陳育紅),et al.Instit Hematol,People’s Hosp,Peking Univ,Beijing 100044. Abstract:Objective To investigate the safety and efficacy of second allogeneic hematopoietic stem cell transplantation for the relapsed hematologic malignancies.Methods The data of 25 relapsed patients received the second allogeneic transplantation as a salvage therapy

  2. Dose escalation to high-risk sub-volumes based on non-invasive imaging of hypoxia and glycolytic activity in canine solid tumors: a feasibility study

    International Nuclear Information System (INIS)

    Glycolytic activity and hypoxia are associated with poor prognosis and radiation resistance. Including both the tumor uptake of 2-deoxy-2-[18 F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer copper(II)diacetyl-bis(N4)-methylsemithio-carbazone (Cu-ATSM) in targeted therapy planning may therefore lead to improved tumor control. In this study we analyzed the overlap between sub-volumes of FDG and hypoxia assessed by the uptake of 64Cu-ATSM in canine solid tumors, and evaluated the possibilities for dose redistribution within the gross tumor volume (GTV). Positron emission tomography/computed tomography (PET/CT) scans of five spontaneous canine solid tumors were included. FDG-PET/CT was obtained at day 1, 64Cu-ATSM at day 2 and 3 (3 and 24 h pi.). GTV was delineated and CT images were co-registered. Sub-volumes for 3 h and 24 h 64Cu-ATSM (Cu3 and Cu24) were defined by a threshold based method. FDG sub-volumes were delineated at 40% (FDG40) and 50% (FDG50) of SUVmax. The size of sub-volumes, intersection and biological target volume (BTV) were measured in a treatment planning software. By varying the average dose prescription to the tumor from 66 to 85 Gy, the possible dose boost (DB) was calculated for the three scenarios that the optimal target for the boost was one, the union or the intersection of the FDG and 64Cu-ATSM sub-volumes. The potential boost volumes represented a fairly large fraction of the total GTV: Cu3 49.8% (26.8-72.5%), Cu24 28.1% (2.4-54.3%), FDG40 45.2% (10.1-75.2%), and FDG50 32.5% (2.6-68.1%). A BTV including the union (∪) of Cu3 and FDG would involve boosting to a larger fraction of the GTV, in the case of Cu3∪FDG40 63.5% (51.8-83.8) and Cu3∪FDG50 48.1% (43.7-80.8). The union allowed only a very limited DB whereas the intersection allowed a substantial dose escalation. FDG and 64Cu-ATSM sub-volumes were only partly overlapping, suggesting that the tracers offer complementing information on tumor physiology. Targeting the

  3. HER-2 and EGFR mRNA Expression and Its Relationship with Versican in Malignant Matrix-Producing Tumors of the Canine Mammary Gland.

    Science.gov (United States)

    Damasceno, Karine Araújo; Ferreira, Enio; Estrela-Lima, Alessandra; Gamba, Conrado de Oliveira; Miranda, Fernanda Freitas; Alves, Mariana Rezende; Rocha, Rafael Malagoli; de Barros, André Luís Branco; Cassali, Geovanni Dantas

    2016-01-01

    Versican expression promotes tumor growth by destabilizing focal cell contacts, thus impeding cell adhesion and facilitating cell migration. It not only presents or recruits molecules to the cell surface, but also modulates gene expression levels and coordinates complex signal pathways. Previously, we suggested that the interaction between versican and human epidermal growth factor receptors may be directly associated with tumor aggressiveness. Thus, the expression of EGFR and HER-2 in these neoplasms may contribute to a better understanding of the progression mechanisms in malignant mammary tumors. The purpose of this study was to correlate the gene and protein expressions of EGFR and HER2 by RNA In Situ Hybridization (ISH) and immunohistochemistry (IHC), respectively, and their relationship with the versican expression in carcinomas in mixed tumors and carcinosarcomas of the canine mammary gland. The results revealed that EGFR mRNA expression showed a significant difference between in situ and invasive carcinomatous areas in low and high versican expression groups. Identical results were observed in HER-2 mRNA expression. In immunohistochemistry analysis, neoplasms with low versican expression showed greater EGFR immunostaining in the in situ areas than in invasive areas, even as the group presenting high versican expression displayed greater EGFR and HER-2 staining in in situ areas. Significant EGFR and HER-2 mRNA and protein expressions in in situ carcinomatous sites relative to invasive areas suggest that these molecules play a role during the early stages of tumor progression. PMID:27490467

  4. (64)Cu-ATSM and (18)FDG PET uptake and (64)Cu-ATSM autoradiography in spontaneous canine tumors

    DEFF Research Database (Denmark)

    Hansen, Anders E; Kristensen, Annemarie T; Jørgensen, Jesper T;

    2012-01-01

    The aim of this study was to compare (64)Cu-diacetyl-bis(N(4)-methylsemicarbazone) ((64)Cu-ATSM) and (18)FDG PET uptake characteristics and (64)Cu-ATSM autoradiography to pimonidazole immunohistochemistry in spontaneous canine sarcomas and carcinomas....

  5. Development of an approach for qualitative and quantitative analysis of trace elements present in canine breast tumors by energy dispersive X-ray fluorescence

    Energy Technology Data Exchange (ETDEWEB)

    Cozer, Thamara C.; Conceicao, Andre L.C.; Paschuk, Sergei A.; Rocha, Anna S.S. da; Fagundes, Alana C.F.; Maciel, Karla F.R.; Pimentel, Gustavo R.O.; Badelli, Juliana C., E-mail: thamara.cozer@gmail.com, E-mail: alconceicao@utfpr.edu.br, E-mail: sergei@utfpr.edu.br, E-mail: anna@utfpr.edu.br, E-mail: alanacarolinef@gmail.com, E-mail: karla_rimanski@hotmail.com, E-mail: g_rop@hotmail.com, E-mail: jubadellin@gmail.com [Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil). Lab. de Espectroscopia de Raio-X

    2015-07-01

    Studies performed with canines indicate that one of the main neoplasia which affect these animals are the breast tumors, representing from 25% to 50% of all kinds of tumors. Moreover, half of them are classified as malignant. In this sense, recent researches on humans have been associated the presence of certain trace elements with the development of breast neoplasia in those individuals. Then, as the breast tissue composition in canines is very similar to the humans, it is expected the same behavior. In this direction, a very effective technique to identify and to determinate trace elements concentration is the EDXRF. However, studies on this area are scarce in the literature. Therefore, in this work it was developed an approach to quantify the main trace elements present into these tumors with high sensitivity. For this purpose, it was determined calibration curves of standards samples diluted in water, with concentrations of Ca, Fe, Cu and Zn, ranging from 400mg/kg to 35mg/kg, from 20mg/kg to 2mg/kg, from 10mg/kg to 1mg/kg and from 100mg/kg to 10mg/kg, respectively. All calibration curves were linearly fitted and on basis in this behavior it was determined the sensitivity of our approach to quantify the concentration of the trace elements mentioned above. In addition, it is important to mention that studies in this area are of great potential, because EDXRF represents a quickly practical and non-destructive alternative to quantify trace elements. (author)

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

    Science.gov (United States)

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

    2016-04-01

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

  7. Dose escalation to high-risk sub-volumes based on non-invasive imaging of hypoxia and glycolytic activity in canine solid tumors

    DEFF Research Database (Denmark)

    Clausen, Malene M.; Hansen, Anders Elias; af Rosenschold, Per Munck;

    2013-01-01

    , the possible dose boost (DB) was calculated for the three scenarios that the optimal target for the boost was one, the union or the intersection of the FDG and 64Cu-ATSM sub-volumes. Results: The potential boost volumes represented a fairly large fraction of the total GTV: Cu3 49.8% (26.8-72.5%), Cu24 28.1% (2...... planning may therefore lead to improved tumor control. In this study we analyzed the overlap between sub-volumes of FDG and hypoxia assessed by the uptake of 64Cu-ATSM in canine solid tumors, and evaluated the possibilities for dose redistribution within the gross tumor volume (GTV). Materials and methods...... defined by a threshold based method. FDG sub-volumes were delineated at 40% (FDG40) and 50% (FDG50) of SUVmax. The size of sub-volumes, intersection and biological target volume (BTV) were measured in a treatment planning software. By varying the average dose prescription to the tumor from 66 to 85 Gy...

  8. SIMPL enhancement of tumor necrosis factor-α dependent p65-MED1 complex formation is required for mammalian hematopoietic stem and progenitor cell function.

    Directory of Open Access Journals (Sweden)

    Weina Zhao

    Full Text Available Significant insight into the signaling pathways leading to activation of the Rel transcription factor family, collectively termed NF-κB, has been gained. Less well understood is how subsets of NF-κB-dependent genes are regulated in a signal specific manner. The SIMPL protein (signaling molecule that interacts with mouse pelle-like kinase is required for full Tumor Necrosis Factor-α (TNFα induced NF-κB activity. We show that SIMPL is required for steady-state hematopoiesis and the expression of a subset of TNFα induced genes whose products regulate hematopoietic cell activity. To gain insight into the mechanism through which SIMPL modulates gene expression we focused on the Tnf gene, an immune response regulator required for steady-state hematopoiesis. In response to TNFα SIMPL localizes to the Tnf gene promoter where it modulates the initiation of Tnf gene transcription. SIMPL binding partners identified by mass spectrometry include proteins involved in transcription and the interaction between SIMPL and MED1 was characterized in more detail. In response to TNFα, SIMPL is found in p65-MED1 complexes where SIMPL enhances p65/MED1/SIMPL complex formation. Together our results indicate that SIMPL functions as a TNFα-dependent p65 co-activator by facilitating the recruitment of MED1 to p65 containing transcriptional complexes to control the expression of a subset of TNFα-induced genes.

  9. Less is more: lymphodepletion followed by hematopoietic stem cell transplant augments adoptive T-cell-based anti-tumor immunotherapy

    OpenAIRE

    Wrzesinski, Claudia; Restifo, Nicholas P

    2005-01-01

    Adoptive T-cell immunotherapy combined with non-myeloablative lymphodepletion has emerged as the most effective immunotherapy treatment for patients with metastatic melanoma (objective response rates of 50%). The mechanisms underlying this major advance in the field of immunotherapy include the elimination of regulatory elements and increased access to activating cytokines. This results in the activation of low-affinity T cells, enabling them to destroy tumors. We propose that a more complete...

  10. Graft-versus-leukemia effects of Wilms' tumor 1 protein-specific cytotoxic T lymphocytes in patients with chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-dong; LI Dan; HUANG Xiao-jun

    2010-01-01

    Background The role of Wilms' tumor 1 protein (WT1)-specific cytotoxic T cells (CTL) in eradicating chronic myeloid leukemia (CML) cells is to be established. The aim of this study was to determine whether WT1 contributed to the graft-versus-leukemia effects (GVLE) for CML following allogeneic hematopoietic stem cell transplantation (HSCT). Methods High-resolution human leukocyte antigen (HLA) class I genotyping was performed by sequence-specific polymerase chain reaction (PCR). Fifteen HLA-A~*2402 patients with CML who underwent allogeneic HSCT were enrolled in this study. We monitored the frequency of WT1-specific CTL by pentamer assay and the molecular minimal residual disease by real-time quantitative PCR.Results A CD8~+ T-cell response to WT1 was observed in 14 of 15 patients after HSCT. The median frequencies of WT1-CTL were 0.54%, 0.62%, 0.81% and 1.28% (%CD8) on days 30, 60, 90 and 180, respectively. The median frequency of WT1-CTL (1.38%) in patients with molecular remission (MoR) was significantly higher than that in those without MoR (0.38%) on day 30, while no significant differences between them were detected on days 60, 90 and 180. The increase of WT1-CTL was associated with a decrease in bcr-abl expression and MoR; and the decrease of WT1-CTL was associated with an increase in bcr-abl expression, suggesting a WT1 -driven GVL effect. WT1-CTL had a predominant effector-memory phenotype (CD45RO~+CD27~-CD57~+).Conclusions The emergence of WT1-CTL with an effector-memory phenotype is associated with GVLE in CML patients after HSCT. This will pave the way for the WT1 vaccines to enhance GVLE after HSCT in CML.

  11. Vincristine modulates the expression of Ki67 and apoptosis in naturally occurring canine transmissible venereal tumor (TVT).

    Science.gov (United States)

    Özalp, G R; Zik, B; Bastan, A; Peker, S; Özdemir-Salci, E S; Bastan, I; Darbaz, I; Salar, S; Karakas, K

    2012-07-01

    We investigated eight adult dogs that were brought to veterinary clinics with a history of transmissible venereal tumors (TVT). Our goal was to demonstrate the occurrence of apoptosis and the cessation of cell proliferation at every phase of scheduled chemotherapy for naturally occurring TVT. Tissue samples were collected immediately after weekly treatments with vincristine sulfate and processed for histological purposes. Sections 5 μm thick were stained by the TUNEL reaction for apoptosis and immunostained for Ki67 as a proliferation marker. We observed that after vincristine applications, tumor cell proliferation ceased and apoptosis increased. Ki67 HSCORE values were significantly lowered after the first and second treatments with the chemotherapeutic agent compared to controls, whereas TUNEL HSCORE values were significantly higher after two applications of vincristine compared to controls. Our results suggest that scheduled vincristine sulfate applications stabilize the induction of tumor regression by inducing apoptosis and preventing cell proliferation.

  12. High Dose Granulocyte Colony-Stimulating Factor Enhances Survival and Hematopoietic Reconstruction in Canines Irradiated by 2.3 Gy Mixed Fission Neutron and Gamma Ray%大剂量粒细胞集落刺激因子对2.3Gy中子γ射线混合照射比格犬存活和造血重建的影响

    Institute of Scientific and Technical Information of China (English)

    李明; 柳晓兰; 赵振虎; 王欣茹; 从玉文; 罗庆良; 余祖胤; 邢爽; 欧红玲; 熊国林; 谢玲; 赵燕芳; 韩阿如娜; 善亚君

    2011-01-01

    This study was purposed to evaluate the effects of recombinant human granulocyte colony-stimulating factor(rhG-CSF)on hematopoietic reconstruction and survival in beagles exposed to mixed fission neutron and γ-ray.13 beagles were unilaterally exposed to single dose of 2.3 Gy 90% neutrons.The experiments were divided into 3 groups:irradiation control group(no any treatment,n=4),supportive care group(n=5)and rhG-CSF plus supportive care group(n=4,abbreviated as rhG-CSF group)in which the beagles were subcutaneously injected with 200 μg/kg of rhG-CSF early at half an hour and 24 hours post-irradiation respectively.The results showed that 2.3 Gy 90% neutron irradiation induced a severe acute radiation sickness of bone marrow type.The administration of rhG-CSF increased the survival rate from 60% in supportive care group to 100%.Twice injection of rhG-CSF in the first 24 hours reduced duration of neutropenia,enhanced neutrophil nadir and promoted neutrophil recovery when compared with control cohort administered clinical support.The number of colony-forming cells(CFU-GM,CFU-E,and BFU-E)in peripheral blood of rhG-CSF treated canines increased 2-to 5-fold relative to those of the supportive care group on day 3.All canines treated with rhG-CSF achieved hematopoietic reconstruction as evidenced by the pathological section of sternum while severe shortage of hemopoietic cells remained in the cohorts given supportive care alone.It is concluded that the combination of supportive care and high-dose rhG-CSF can accelerate hematopoietic recovery and enhance survival of dogs exposed to 2.3 Gy mixed neutron and gamma ray

  13. TU-C-12A-11: Comparisons Between Cu-ATSM PET and DCE-CT Kinetic Parameters in Canine Sinonasal Tumors

    Energy Technology Data Exchange (ETDEWEB)

    La Fontaine, M; Bradshaw, T [University of Wisconsin, Madison, Wisconsin (United States); Kubicek, L [University of Florida, Gainesville, Florida (United States); Forrest, L [University of Wisconsin-Madison, Madison, Wisconsin (United States); Jeraj, R [University of Wisconsin, Madison, WI (United States)

    2014-06-15

    Purpose: Regions of poor perfusion within tumors may be associated with higher hypoxic levels. This study aimed to test this hypothesis by comparing measurements of hypoxia from Cu-ATSM PET to vasculature kinetic parameters from DCE-CT kinetic analysis. Methods: Ten canine patients with sinonasal tumors received one Cu-ATSM PET/CT scan and three DCE-CT scans prior to treatment. Cu-ATSM PET/CT and DCE-CT scans were registered and resampled to matching voxel dimensions. Kinetic analysis was performed on DCE-CT scans and for each patient, the resulting kinetic parameter values from the three DCE-CT scans were averaged together. Cu-ATSM SUVs were spatially correlated (r{sub spatial}) on a voxel-to-voxel basis against the following DCE-CT kinetic parameters: transit time (t{sub 1}), blood flow (F), vasculature fraction (v{sub 1}), and permeability (PS). In addition, whole-tumor comparisons were performed by correlating (r{sub ROI}) the mean Cu-ATSM SUV (SUV{sub mean}) with median kinetic parameter values. Results: The spatial correlations (r{sub spatial}) were poor and ranged from -0.04 to 0.21 for all kinetic parameters. These low spatial correlations may be due to high variability in the DCE-CT kinetic parameter voxel values between scans. In our hypothesis, t{sub 1} was expected to have a positive correlation, while F was expected to have a negative correlation to hypoxia. However, in wholetumor analysis the opposite was found for both t{sub 1} (r{sub ROI} = -0.25) and F (r{sub ROI} = 0.56). PS and v{sub 1} may depict angiogenic responses to hypoxia and found positive correlations to Cu-ATSM SUV for PS (r{sub ROI} = 0.41), and v{sub 1} (r{sub ROI} = 0.57). Conclusion: Low spatial correlations were found between Cu-ATSM uptake and DCE-CT vasculature parameters, implying that poor perfusion is not associated with higher hypoxic regions. Across patients, the most hypoxic tumors tended to have higher blood flow values, which is contrary to our initial hypothesis. Funding

  14. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  15. The use of {sup 99m}Tc-thymine to identify metastatic disease in dogs presenting the cutaneous form of canine transmissible venereal tumor; Uso da {sup 99m}Tc-timina na identificacao de metastases de tumor venereo transmissivel canino com apresentacao cutanea

    Energy Technology Data Exchange (ETDEWEB)

    Castelo-Branco, Paulo S.M. [Universidade Estacio de Sa, Rio de Janeiro, RJ (Brazil)]. E-mail: p.castelobranco@ig.com.br; Castro, Veronica; Sena, Priscila [Sociedade Uniao Internacional Protetora dos Animais (SUIPA), Rio de Janeiro, RJ (Brazil); Souza, Sergio A. Lopes de; Lopes, Flavia P.P. Lobo; Pereira, Joao Batista; Fonseca, Lea M. Barbosa da; Gutfilen, Bianca [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil). Dept. de Radiologia

    2008-08-15

    The venereal canine transmissible tumor (VCTT) is described in literature as a rare metastatic tumor. However accurate methods for verification of this affirmative are not available in the veterinary medicine routine. In this study, we evaluated the dissemination from VCTT with cutaneous presentation using the {sup 99m}Tc-Thymine scintigraphy. The labelled thymine was up taken by the three cases of VCTT. {sup 99m}Tc-Thymine is a promising imaging technique for non-invasive veterinarian evaluation of tumoral dissemination degree decurrent from the VCTT cases. (author)

  16. Apoptosis in the transplanted canine transmissible venereal tumor during growth and regression phases Apoptose no tumor venéreo transmissível canino durante as fases de crescimento e regressão

    Directory of Open Access Journals (Sweden)

    F.G.A. Santos

    2008-06-01

    Full Text Available Twelve male, mongrel, adult dogs were subcutaneously transplanted with cells originated from two canine transmissible venereal tumors (TVT. The aim was to demonstrate and to quantify the occurrence of apoptosis in the TVT regression. After six months of transplantation, a tumor sample was obtained from each dog, being six dogs with TVT in the growing phase and six in the regression phase as verified by daily measurements. Samples were processed for histological and ultrastructural purposes as well as for DNA extraction. Sections of 4µm were stained by HE, Shorr, methyl green pyronine, Van Gieson, TUNEL reaction and immunostained for P53. The Shorr stained sections went through morphometry that demonstrated an increase of the apoptotic cells per field in the regressive tumors. It was also confirmed by transmission electron microscopy, which showed cells with typical morphology of apoptosis and by the TUNEL reaction that detected in situ the 3'OH nick end labeling mainly in the regressive tumors. The regressive TVTs also showed an intensified immunostaining for P53 besides a more intense genomic DNA fragmentation detected by the agarose gel electrophoresis. In conclusion, apoptosis has an important role in the regression of the experimental TVT in a way that is P53-dependent.Doze cães, adultos, machos e sem raça definida foram transplantados subcutaneamente, na região hipogástrica, com células originadas de dois tumores venéreos transmissíveis caninos (TVT. O objetivo do estudo foi demonstrar e quantificar a ocorrência de apoptose na regressão do TVT. Após seis meses, foi obtido um tumor de cada animal, totalizando seis em crescimento e seis em regressão. Fragmentos dos tumores foram processados para avaliação histológica, ultra-estrutural e também para extração de DNA. Cortes de 4µm foram corados em HE, Shorr, verde de metila pironina e Van Gieson e alguns foram submetidos à reação do TUNEL e à imunoistoquímica para P53

  17. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

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

    Science.gov (United States)

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

    2015-11-01

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

  19. Inflammation- and tumor-induced anorexia and weight loss require MyD88 in hematopoietic/myeloid cells but not in brain endothelial or neural cells.

    Science.gov (United States)

    Ruud, Johan; Wilhelms, Daniel Björk; Nilsson, Anna; Eskilsson, Anna; Tang, Yan-Juan; Ströhle, Peter; Caesar, Robert; Schwaninger, Markus; Wunderlich, Thomas; Bäckhed, Fredrik; Engblom, David; Blomqvist, Anders

    2013-05-01

    Loss of appetite is a hallmark of inflammatory diseases. The underlying mechanisms remain undefined, but it is known that myeloid differentiation primary response gene 88 (MyD88), an adaptor protein critical for Toll-like and IL-1 receptor family signaling, is involved. Here we addressed the question of determining in which cells the MyD88 signaling that results in anorexia development occurs by using chimeric mice and animals with cell-specific deletions. We found that MyD88-knockout mice, which are resistant to bacterial lipopolysaccharide (LPS)-induced anorexia, displayed anorexia when transplanted with wild-type bone marrow cells. Furthermore, mice with a targeted deletion of MyD88 in hematopoietic or myeloid cells were largely protected against LPS-induced anorexia and displayed attenuated weight loss, whereas mice with MyD88 deletion in hepatocytes or in neural cells or the cerebrovascular endothelium developed anorexia and weight loss of similar magnitude as wild-type mice. Furthermore, in a model for cancer-induced anorexia-cachexia, deletion of MyD88 in hematopoietic cells attenuated the anorexia and protected against body weight loss. These findings demonstrate that MyD88-dependent signaling within the brain is not required for eliciting inflammation-induced anorexia. Instead, we identify MyD88 signaling in hematopoietic/myeloid cells as a critical component for acute inflammatory-driven anorexia, as well as for chronic anorexia and weight loss associated with malignant disease.

  20. Protocol for the anatomopathological examination of canine mammary tumors Protocolo para exame anatomopatológico de tumores mamários em cães

    Directory of Open Access Journals (Sweden)

    E. Ferreira

    2003-02-01

    Full Text Available Foi elaborado um protocolo para exame anatomopatológico de tumores de mama em cães, constituído de três partes: requisição, exame clínico e laudo histopatológico. O exame clínico contém dados sobre a descrição macroscópica da lesão. O laudo histopatológico constituiu-se de campos para descrição microscópica pormenorizada das lesões e classificação da principal lesão observada. A elaboração do protocolo tem como objetivo estabelecer critérios para estudos e pesquisas sobre neoplasias mamárias em animais e auxiliar no diagnóstico e prognóstico de lesões mamárias.

  1. In vivo anti-tumor activity of marine hematopoietic stem cells expressing a p185HER2-specific chimeric T-cell receptor gene

    Institute of Scientific and Technical Information of China (English)

    JIAN MIN YANG; MICHAEL S FRIEDMAN; MARIANNE T HUBEN; JENNIFER FULLER; QIAO LI; ALFRED E CHANG; JAMES J MULE; KEVIN T MCDONAGH

    2006-01-01

    We have confirmed efficient anti-tumor activities of the peripheral lymphocytes transduced with a p185HER2-specific chimeric T-cell receptor gene both in murine and in human in our previous studies. To further test the feasibility of chimeric T-cell receptor in a bone marrow transplantation model, we first, made two murine tumor cell lines: MT901 and MCA-205, to express human p185HER2by retroviral gene transduction. Murine bone marrow cells were retrovirally transduced to express the chimeric T-cell receptor and gene-modified bone marrow cells were transplanted into lethally irradiated mouse. Six months post transplantation, p185HER2-positive tumor cells: MT-901/HER2 or MCA-205/HER2 was subcutaneously or intravenously injected to make mouse models simulating primary breast cancer or pulmonary metastasis. The in vivo anti-tumor effects were monitored by the size of the subcutaneous tumor or counting the tumor nodules in the lungs after India ink staining. The size of the subcutaneous tumor was significantly inhibited and the number of pulmonary nodules were significantly decreased in mouse recipients transplanted with chimeric T-cell receptor modified bone marrow cells compared with the control group. Our results suggest the efficient in vivo anti-tumor activities of chimeric T-cell receptor gene modified bone marrow cells.

  2. Expression of P-glycoprotein, multidrug resistance-associated protein, glutathione-S-transferase pi and p53 in canine transmissible venereal tumor

    Directory of Open Access Journals (Sweden)

    Daniel G. Gerardi

    2014-01-01

    Full Text Available The overexpression of proteins P-glycoprotein (P-gp, multidrug resistance-associated protein (MRP1, mutant p53, and the enzyme glutathione-S-transferase (GSTpi are related to resistance to chemotherapy in neoplasms. This study evaluated the expression of these markers by immunohistochemistry in two groups of canine TVT, without history of prior chemotherapy (TVT1, n=9 and in TVTs presented unsatisfactory clinical response to vincristine sulfate (TVT2, n=5. The percentage of specimens positively stained for P-gp, MRP1, GSTpi and p53 were, respectively 88.8%, 0%, 44.5% and 22.2% in TVT1 and 80%, 0%, 80% and 0% in TVT2. In TVT1, one specimen presented positive expression for three markers and four specimens for two markers. In TVT2, three specimens expressed P-gp and GSTpi. In conclusion, the canine TVTs studied expressed the four markers evaluated, but just P-gp and GSTpi were significantly expressed, mainly at cytoplasm and cytoplasm and nuclei, respectively, either before chemotherapy as after vincristine sulfate exposure. Future studies are needed to demonstrate the function of these two markers in conferring multidrug resistance (MDR or predict the response to chemotherapy in canine TVT.

  3. SECOND MALIGNANCIES AFTER AUTOLOGOUS HEMATOPOIETIC CELL TRANSPLANTATION IN CHILDREN

    OpenAIRE

    Danner-Koptik, Karina E; Majhail, Navneet S.; Brazauskas, Ruta; Wang, Zhiwei; Buchbinder, David; Cahn, Jean-Yves; Dilley, Kimberley J.; Frangoul, Haydar A.; Gross, Thomas G.; Hale, Gregory A.; Hayashi, Robert J.; Hijiya, Nobuko; Kamble, Rammurti T.; Lazarus, Hillard M.; Marks, David I.

    2012-01-01

    Childhood autologous hematopoietic cell transplant (AHCT) survivors can be at risk for secondary malignant neoplasms (SMNs). We assembled a cohort of 1,487 pediatric AHCT recipients to investigate the incidence and risk factors for SMNs. Primary diagnoses included neuroblastoma (39%), lymphoma (26%), sarcoma (18%), CNS tumors (14%), and Wilms tumor (2%). Median follow-up was 8 years (range,

  4. Transplante de células-tronco hematopoéticas para tumores sólidos: recomendações do Consenso Brasileiro de Transplante de Medula Óssea Autologous hematopoietic stem cell transplantation in solid tumors: the Brazilian Consensus on Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Décio Lerner

    2010-05-01

    Full Text Available O transplante de células-tronco hematopoéticas autólogo permite o escalonamento de dose de drogas quimioterápicas e é uma estratégia atraente para tratamento de tumores sólidos, principalmente em doenças recaídas. Não há, no entanto, estudos randomizados fase III que demonstrem benefício deste procedimento em tumor sólido. Em tumor germinativo de testículo, há estudos fase II com excelentes resultados, proporcionando cura para doentes refratários a platina ou que estão em terceira linha de quimioterapia. Com base nisto, o transplante de células-tronco hematopoéticas autólogo é considerado tratamento padrão para tumor germinativo recaído. Para câncer de mama, o papel desta modalidade de tratamento permanece controverso apesar dos vinte anos de experiência. Ainda é utilizado em ensaios clínicos e talvez exista algum subgrupo que se beneficie. O procedimento não oferece benefício para câncer de ovário, pulmão ou tumor cerebral. O transplante alogeneico de células-tronco hematopoéticas para tumores sólidos se baseia no efeito enxerto-contra-tumor, que é observado para algumas doenças: câncer mamário, colorretal, ovariano, pancreático e, finalmente, renal, em que há a maior experiência. Porém, o tratamento ainda é considerado experimental.Autologous hematopoietic stem cell transplantation, which allows chemotherapy dose-escalonation, is an attractive strategy for solid tumors treatment, specially relapsed diseases. However, there are no phase III trials showing benefits. There are phase II trials showing excellent results for germ cell tumors, including cure for platinrefractory and heavily pretreated patients. Because of this, autologous stem cell transplantation is considered standard of care for relapsed germ cell tumor. The role of this treatment remains controversial for breast cancer despite twenty years of experience. It’s still done in clinical trials and it may benefit a subgroup of patients. The

  5. Optimization of methods to assess mitochondrial DNA in archival paraffin-embedded tissues from mammary canine tumors Otimização dos métodos para avaliar o DNA mitocondrial obtido a partir de tumores mamários caninos incluídos em parafina

    Directory of Open Access Journals (Sweden)

    Angélica C. Bertagnolli

    2008-08-01

    Full Text Available In this study we describe the alterations used to extract and amplify mitochondrial desoxyribonucleic acid (DNA from formalin-fixed paraffin-embedded samples of canine mammary tumors. The epithelial and mesenchymal components (chondromyxoid and chondroid of each tumor, as well as the normal mammary gland tissues, were manually microdissected from 19 mixed canine mammary tumors (10 benign mixed tumors and nine carcinomas arising in mixed tumors. DNA was extracted by Invisorb® Spin Tissue Mini Kit, with protocol changes proposed by the manufacturer. A 273-bp fragment was amplified by polymerase chain reaction (PCR and submitted to automatic sequence analysis. The fragment was successfully analyzed in 100% of the samples. However, an additional lysis step, the reduction of volume in buffer solutions and PCR, a higher annealing temperature and an increase in the number of PCR cycles were required. The initial PCR products were diluted and re-amplified in six samples so that they could be successfully analyzed.A presente comunicação descreve as modificações usadas para extrair e amplificar o DNA mitocondrial obtido de amostras de tumores mamários caninos fixados em formol tamponado a 10% e incluídos em parafina. Os componentes epiteliais e mesenquimais (condromixóide e condróide, bem como a mama normal adjacente, foram microdissectados manualmente de 19 tumores mamários (10 tumores mistos benignos e nove carcinomas em tumores mistos. O DNA foi extraído utilizando-se o Invisorb® Spin Tissue Mini Kit com modificações do protocolo proposto pelo fabricante. Um fragmento de 273-pb foi amplificado por reação em cadeia da polimerase (PCR e seqüenciado em seqüenciador automático. O fragmento foi analisado em 100% das amostras, entretanto modificações como lise adicional, redução do volume das soluções de extração e PCR, aumento da temperatura de anelamento e do número de ciclos de amplificação foram necessárias. Em seis

  6. Anti-thymocyte globulin could improve the outcome of allogeneic hematopoietic stem cell transplantation in patients with highly aggressive T-cell tumors

    International Nuclear Information System (INIS)

    The early experiment result in our hospital showed that anti-thymocyte globulin (ATG) inhibited the proliferation of lymphoid tumor cells in the T-cell tumors. We used the ATG as the part of the conditioning regimen and to evaluate the long-term anti-leukemia effect, the safety and complication in the patients with highly aggressive T-cell lymphomas. Twenty-three patients were enrolled into this study. At the time of transplant, six patients reached first or subsequent complete response, three patients had a partial remission and 14 patients had relapsed or primary refractory disease. The conditioning regimen consisted of ATG, total body irradiation, toposide and cyclophosphamide. The complete remission rate after transplant was 95.7%. At a median follow-up time of 25 months, 16 (69.6%) patients are alive and free from diseases, including nine patients in refractory and progressive disease. Seven patients died after transplant, five from relapse and two from treatment-related complications. The incidence of grades II–IV acute graft-vs-host disease (GvHD) was 39.1%. The maximum cumulative incidence of chronic GvHD was 30%. The most frequent and severe conditioning-related toxicities observed in 8 out of 23 patients were grades III/IV infections during cytopenia. Thus, ATG-based conditioning is a feasible and effective alternative for patients with highly aggressive T-cell tumors

  7. The Relevance of CD117-Immunocytochemistry Staining Patterns to Mutational Exon-11 in c-kit Detected by PCR from Fine-Needle Aspirated Canine Mast Cell Tumor Cells

    Directory of Open Access Journals (Sweden)

    A. Sailasuta

    2014-01-01

    Full Text Available Canine cutaneous mast cell tumors (MCT are the lethal skin tumors. The biological behavior of the MCT cells is quite varied and unpredictable. Almost MCT dogs usually require a rapid diagnosis and therapy. However, MCT diagnosis and prognosis are still dependent on histopathology which is rather inconvenient, time-consuming, painful, and harmful for some cases. Indeed, MCT can be easily accessible using fine-needle aspiration (FNA. In this study, our biopsy specimens were classified as low- and high-grade MCT based on the novel 2-tier histopathologic grading system. We have demonstrated the usage of fine-needle aspirated MCT cells (FNA-MCT cells from these specimens as a primary cell source to study the distribution of CD117-immunocytochemistry (CD117-ICC staining patterns and the frequency of internal tandem duplication- (ITD- mutant exon-11 of c-kit. The result has substantially shown that there were three staining patterns identified in the cells. Only paranuclear pattern was significantly increased in the cells from high-grade MCT. Altogether, the ITD-mutant exon-11 was also detectable only in these cells. Therefore, the result has supported our hypothesis that there was an increased opportunity to observe a higher CD117-ICC staining pattern and exon-11 mutation in high-grade MCT; even these two parameters may not precisely indicate a histopathological grade.

  8. Oncolytic Virotherapy of Canine and Feline Cancer

    Directory of Open Access Journals (Sweden)

    Ivaylo Gentschev

    2014-05-01

    Full Text Available Cancer is the leading cause of disease-related death in companion animals such as dogs and cats. Despite recent progress in the diagnosis and treatment of advanced canine and feline cancer, overall patient treatment outcome has not been substantially improved. Virotherapy using oncolytic viruses is one promising new strategy for cancer therapy. Oncolytic viruses (OVs preferentially infect and lyse cancer cells, without causing excessive damage to surrounding healthy tissue, and initiate tumor-specific immunity. The current review describes the use of different oncolytic viruses for cancer therapy and their application to canine and feline cancer.

  9. Investigation on Canine Tumors in Hangzhou from 2012 to 2014%2012年-2014年杭州地区宠物犬肿瘤调查

    Institute of Scientific and Technical Information of China (English)

    朱国; 师福山; 杨杨

    2015-01-01

    在浙江大学附属动物医院门诊收集了133例犬肿瘤自然发生病例,通过对其临床症状、发病部位、品种、年龄、性别、饮食等进行调查。发现肿瘤发病早期一般不表现全身症状,恶性肿瘤发生转移时会有恶病质的表现;乳腺和皮肤及软组织是犬肿瘤临床高发的部位,分别占全部患犬的42.11%和24.81%;京巴犬、杂交犬、贵宾犬、西施犬和可卡犬是肿瘤高发品种,分别占患犬的19.55%、14.29%、11.28%、7.52%和6.77%;患病犬年龄1岁~15岁,平均年龄9.39岁,6岁~10岁发病率最高;一些肿瘤类型与性别、是否绝育有关;日常饮食与犬肿瘤的发生有关,肉拌饭类、纯肉加火腿肠类、狗粮加肉类和纯狗粮类,发病比例分别为39.85%、26.32%、21.05%和12.78%,纯狗粮饲养的犬发病率较低。%In order to investigate the epidemiology of canine tumors,we examined 133 cases of canine tumors from animal hospital of Zhejiang University and studied the relationship between tumors and clinical symptoms,species, genders,ages and diets.Our results indicated that animals with neoplastic diseases show no general systemic symptoms in the early stages of diseases,but cachexia was invariably observed at metastatic stage.The most com-mon locations of the tumors are:mammary glands (42.11% of the cases),skin and soft tissues (24.81%).The most affected breeds,in decreasing order of frequency,were pekingese (19.55%),hybrids (14.29%),poodles (11.28%),shih tzu (7.52%)and cocker spaniel (6.77%).The age of tumor ocurrence extends from 1 to 15 years old,with the most frequent occurrence being in the age group of 6 to 10 years old,and an average age of 9.39 years old .The occurrence of the tumors depends also on a daily diet :meat with rice diet shows the highest rate (39.85%),whereas meat plus ham/ sausages (26.32%)and dog food plus meat (21.05%)were associated with

  10. Molecular portrait-based correlation between primary canine mammary tumor and its lymph node metastasis: possible prognostic-predictive models and/or stronghold for specific treatments?

    Directory of Open Access Journals (Sweden)

    Beha Germana

    2012-11-01

    Full Text Available Abstract Background This study aimed to evaluate the relationship between the molecular phenotype of the primary mammary tumor and its related lymph node metastasis in the dog to develop prognostic-predictive models and targeted therapeutic options. Results Twenty mammary tumor samples and their lymph node metastases were selected and stained by immunohistochemistry with anti-estrogen receptor (ER, -progesterone receptor (PR, -human epidermal growth factor receptor 2 (c-erbB-2, -cytokeratin 5/6 (CK 5/6, -cytokeratin 14 (CK14, -cytokeratin 19 (CK 19 and -protein 63 (p63 antibodies. Four phenotypes (luminal A, luminal B, c-erbB2 overexpressing and basal-like were diagnosed in primary tumors and five (luminal A, luminal B, c-erbB-2 overexpressing, basal-like and normal-like in the lymph node metastases. Phenotypic concordance was found in 13 of the 20 cases (65%, and seven cases (35% showed discordance with different lymph node phenotypic profile from the primary tumor. Conclusions The phenotype of the primary tumor assumes a predictive-therapeutic role only in concordant cases, meaning that both the primary tumor and its lymph node metastasis should be evaluated at the same time. A treatment plan based only on the primary tumor phenotype could lead to therapeutic failures if the phenotype of the lymph node metastasis differs from that of the primary tumor.

  11. Tumor

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008479 Preliminary study of MR elastography in brain tumors. XU Lei(徐磊), et al.Neurosci Imaging Center, Beijing Tiantan Hosp, Capital Med Univ, Beijing 100050.Chin J Radiol 2008;42(6):605-608. Objective To investigate the potential values of magnetic resonance elastography (MRE) for evaluating the brain tumor consistency in vivo. Methods Fourteen patients with known solid brain tumor (5 male, 9 female; age range: 16-63 years)

  12. Distribution and activity levels of matrix metalloproteinase 2 and 9 in canine and feline osteosarcoma

    OpenAIRE

    Gebhard, Christiane; Fuchs-Baumgartinger, Andrea; Razzazi-Fazeli, Ebrahim; Miller, Ingrid; Walter, Ingrid

    2016-01-01

    Overexpression of matrix metalloproteinases (MMPs) has been associated with increased tumor aggressiveness and metastasis dissemination. We investigated whether the contrasting metastatic behavior of feline and canine osteosarcoma is related to levels and activities of MMP2 and MMP9. Zymography and immunohistochemistry were used to determine expression levels of MMP2 and MMP9 in canine and feline osteosarcoma. Using immunohistochemistry, increased MMP9 levels were identified in most canine os...

  13. Intratumoral CD3+ T-lymphocytes immunoexpression and its association with c-Kit, angiogenesis, and overall survival in malignant canine mammary tumors.

    Science.gov (United States)

    Carvalho, Maria Isabel; Pires, Isabel; Dias, Marlene; Prada, Justina; Gregório, Hugo; Lobo, Luis; Queiroga, Felisbina

    2015-01-01

    In this study 80 malignant CMT were submitted to immunohistochemical detection of CD3, c-kit, VEGF, and CD31, together with clinicopathological parameters of tumor aggressiveness. CD3+ T-cells and c-kit overexpression revealed a positive correlation with VEGF (r = 0.503, P < 0.0001; r = 0.284, P = 0.023 for CD3 and c-kit, resp.) and CD31 (r = 0.654, P < 0.0001; r = 0.365, P = 0.003 for CD3 and c-kit, resp.). A significant association (P = 0.039) and a positive correlation (r = 0.263, P = 0.039) between CD3 and c-kit were also observed. High CD3/VEGF, c-kit/VEGF, and CD3/c-kit tumors were associated with elevated grade of malignancy (P < 0.0001 for all groups), presence of intravascular emboli (P < 0.0001 for CD3/VEGF and CD3/c-kit; P = 0.002 for c-kit/VEGF), and presence of lymph node metastasis (P < 0.0001 for all groups). Tumors with high CD3/VEGF (P = 0.006), c-kit/VEGF (P < 0.0001), and CD3/c-kit (P = 0.002) were associated with poor prognosis. Interestingly high c-kit/VEGF tumors retained their significance by multivariate analysis arising as independent prognostic factor. PMID:26346272

  14. Intratumoral CD3+ T-Lymphocytes Immunoexpression and Its Association with c-Kit, Angiogenesis, and Overall Survival in Malignant Canine Mammary Tumors

    Directory of Open Access Journals (Sweden)

    Maria Isabel Carvalho

    2015-01-01

    Full Text Available In this study 80 malignant CMT were submitted to immunohistochemical detection of CD3, c-kit, VEGF, and CD31, together with clinicopathological parameters of tumor aggressiveness. CD3+ T-cells and c-kit overexpression revealed a positive correlation with VEGF (r = 0.503, P < 0.0001; r = 0.284, P = 0.023 for CD3 and c-kit, resp. and CD31 (r = 0.654, P < 0.0001; r = 0.365, P = 0.003 for CD3 and c-kit, resp.. A significant association (P = 0.039 and a positive correlation (r = 0.263, P = 0.039 between CD3 and c-kit were also observed. High CD3/VEGF, c-kit/VEGF, and CD3/c-kit tumors were associated with elevated grade of malignancy (P < 0.0001 for all groups, presence of intravascular emboli (P < 0.0001 for CD3/VEGF and CD3/c-kit; P = 0.002 for c-kit/VEGF, and presence of lymph node metastasis (P < 0.0001 for all groups. Tumors with high CD3/VEGF (P = 0.006, c-kit/VEGF (P < 0.0001, and CD3/c-kit (P = 0.002 were associated with poor prognosis. Interestingly high c-kit/VEGF tumors retained their significance by multivariate analysis arising as independent prognostic factor.

  15. Syndrome-Associated Tumors by Organ System.

    Science.gov (United States)

    Gonzalez, Raul S; Riddle, Nicole D

    2016-06-01

    Certain tumors suggest the possibility of a patient harboring a genetic syndrome, particularly in children. Syndrome-associated tumors of the gastrointestinal tract, genitourinary tract, gynecologic tract, heart, lungs, brain, eye, endocrine organs, and hematopoietic system will be briefly discussed.

  16. A Comparison of Fresh Frozen vs. Formalin-Fixed, Paraffin-Embedded Specimens of Canine Mammary Tumors via Branched-DNA Assay

    OpenAIRE

    Florenza Lüder Ripoli; Annika Mohr; Susanne Conradine Hammer; Saskia Willenbrock; Marion Hewicker-Trautwein; Silvia Hennecke; Hugo Murua Escobar; Ingo Nolte

    2016-01-01

    Mammary neoplasms are the tumors most affecting female dogs and women. Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable source of archived biological material. Fresh frozen (FF) tissue is considered ideal for gene expression analysis. However, strategies based on FFPE material offer several advantages. Branched-DNA assays permit a reliable and fast workflow when analyzing gene expression. The aim of this study was to assess the comparability of the branched-DNA assay when an...

  17. Chiaroscuro hematopoietic stem cell.

    OpenAIRE

    Quesenberry, P.; Habibian, M. (PhD); Dooner, M; Zhong, S.; Reilly, J; Peters, S.; De Becker, P; Grimaldi, C.; Carlson, J; REDDY, P; Nilsson, S.; Stewart, F. M.

    1998-01-01

    These observations suggest several immediate clinical strategies. In gene therapy, approaches could be targeted to obtain cycling of hematopoietic stem cells and gene-carrying retrovirus vector integration followed by engraftment at an appropriate time interval which favors engraftment. The same type of approach can be utilized for stem cell expansion approaches. Alternatively marrow or peripheral stem cell engraftment can be obtained with minimal to no toxicity in allochimeric strategies in ...

  18. Hematopoietic stem cell transplantation

    OpenAIRE

    Eleftheria Hatzimichael; Mark Tuthill

    2010-01-01

    Eleftheria Hatzimichael1, Mark Tuthill21Department of Haematology, Medical School of Ioannina, University of Ioannina, Ioannina, Greece; 2Department of Medical Oncology, Hammersmith Hospital, Imperial College National Health Service Trust, London, UKAbstract: More than 25,000 hematopoietic stem cell transplantations (HSCTs) are performed each year for the treatment of lymphoma, leukemia, immune-deficiency illnesses, congenital metabolic defects, hemoglobinopathies, and myelodysplastic and mye...

  19. Immunohistochemical expression of B and T-lymphocytes and TGF-β in experimentally transplanted canine venereal tumor Expressão imunoistoquímica de linfócitos T e B e do TGF-β no tumor venéreo transmissível canino experimentalmente transplantado

    Directory of Open Access Journals (Sweden)

    Ana Carolina Trompieri Silveira

    2009-07-01

    Full Text Available The tumor/host relationship may have a determining role in the progression or remission of a tumor. Greater infiltration of leukocytes into tumors has been associated with a better prognosis, although controversy regarding whether these cells have a central role in antitumor immunity still exists. Canine transmissible venereal tumor (TVT is an experimentally transplantable type of tumor that has been used as an experimental model for the tumor/host relationship. The aim of this study was to evaluate the infiltration of T-lymphocytes (CD3, CD4, CD8 and B lymphocytes (CD79-α and the expression of the cytokine TGF-β in TVT, by means of immunohistochemistry (ABC method. The experimental tumors were composed of puppies that developed TVT after transplantation, in the progression (n=8 (Group 1a, latency (n=8 (Group 1b and regression (n=8 (Group 1c phases of the tumor. CD3+ T-lymphocytes predominated in the progression and regression phases, in relation to the latency phase. CD4+ and ¹CD8+ T-lymphocytes were predominant in the progression phase, and with lower expression in the regression phase. The greatest quantities of B-lymphocytes were in the regression phase, with restricted expression in the progression phase. TGF-β was expressed equally in the phases of the transplanted TVT.A relação tumor/hospedeiro pode ter um papel determinante na progressão ou remissão de um tumor. Uma maior infiltração de leucócitos nos tumores tem sido associada a um melhor prognóstico. Entretanto, o papel central dessas células na imunidade antitumoral ainda é controverso. O tumor venéreo transmissível (TVT canino é um tumor transplantável experimentalmente e tem sido utilizado como modelo experimental da relação tumor versus hospedeiro. O objetivo deste estudo foi avaliar a infiltração de linfócitos T (CD3, CD4, CD8, B (CD79-α e a expressão da citocina TGF-β no TVT por meio da imunoistoquímica (método ABC. Os grupos experimentais foram

  20. FDG PET/CT imaging in canine cancer patients

    DEFF Research Database (Denmark)

    Hansen, Anders Elias; McEvoy, Fintan; Engelholm, Svend Aage;

    2011-01-01

    and organs in canine cancer patients. FDG PET/CT was performed in 14 dogs including, nine mesenchymal tumors, four carcinomas, and one incompletely excised mast cell tumor. A generally higher FDG uptake was observed in carcinomas relative to sarcomas. Maximum SUV of carcinomas ranged from 7.6 to 27.......0, and for sarcomas from 2.0 to 10.6. The FDG SUV of several organs and tissues, including regional brain uptake is reported, to serve as a reference for future FDG PET studies in canine cancer patients. Several potential pitfalls have been recognized in interpretation of FDG PET images of human patients, a number...

  1. Cytological diagnosis of a metastatic canine mammary tumor in pleural effusion Diagnóstico citológico de tumor mamário metastático canino em derrame pleural

    OpenAIRE

    Cassali, G.D.; Gärtner, F.; M.J. Vieira da Silva; Schmitt, F C

    1999-01-01

    Descrevem-se os achados citomorfológicos de um tumor maligno de mama em uma cadela Poodle de sete anos de idade, o qual foi observado inicialmente pelo exame citológico do derrame pleural. Comparam-se os aspectos citológicos do derrame pleural e punção aspirativa com agulha fina do tumor com aqueles descritos para o câncer de mama na espécie humana.

  2. Cytological diagnosis of a metastatic canine mammary tumor in pleural effusion Diagnóstico citológico de tumor mamário metastático canino em derrame pleural

    Directory of Open Access Journals (Sweden)

    G.D. Cassali

    1999-08-01

    Full Text Available Descrevem-se os achados citomorfológicos de um tumor maligno de mama em uma cadela Poodle de sete anos de idade, o qual foi observado inicialmente pelo exame citológico do derrame pleural. Comparam-se os aspectos citológicos do derrame pleural e punção aspirativa com agulha fina do tumor com aqueles descritos para o câncer de mama na espécie humana.

  3. Propofol attenuates LPS-induced tumor necrosis factor-α, interleukin-6 and nitric oxide expression in canine peripheral blood mononuclear cells possibly through down-regulation of nuclear factor (NF)-κB activation

    OpenAIRE

    Pei, Zengyang; WANG, Jinqiu

    2014-01-01

    Sepsis is a major cause of mortality in intensive care medicine. Propofol, an intravenous general anesthetic, has been suggested to have anti-inflammatory properties and able to prevent sepsis induced by Gram-positive and Gram-negative bacteria by down-regulating the gene expression of pro-inflammatory cytokines. However, propofol’s anti-inflammatory effects upon canine peripheral blood mononuclear cells (PBMCs) have not yet been clarified. Here, we isolate canine PBMCs and investigate the ef...

  4. Distribution and activity levels of matrix metalloproteinase 2 and 9 in canine and feline osteosarcoma.

    Science.gov (United States)

    Gebhard, Christiane; Fuchs-Baumgartinger, Andrea; Razzazi-Fazeli, Ebrahim; Miller, Ingrid; Walter, Ingrid

    2016-01-01

    Overexpression of matrix metalloproteinases (MMPs) has been associated with increased tumor aggressiveness and metastasis dissemination. We investigated whether the contrasting metastatic behavior of feline and canine osteosarcoma is related to levels and activities of MMP2 and MMP9. Zymography and immunohistochemistry were used to determine expression levels of MMP2 and MMP9 in canine and feline osteosarcoma. Using immunohistochemistry, increased MMP9 levels were identified in most canine osteosarcomas, whereas cat samples more often displayed moderate levels. High levels of pro-MMP9, pro-MMP2, and active MMP2 were detected by gelatin zymography in both species, with significantly higher values for active MMP2 in canine osteosarcoma. These findings indicate that MMP2 is probably involved in canine and feline osteosarcoma and their expression and activity could be associated with the different metastatic behavior of canine and feline osteosarcoma. PMID:26733734

  5. Intratumoral CD3+ T-Lymphocytes Immunoexpression and Its Association with c-Kit, Angiogenesis, and Overall Survival in Malignant Canine Mammary Tumors

    OpenAIRE

    Maria Isabel Carvalho; Isabel Pires; Marlene Dias; Justina Prada; Hugo Gregório; Luis Lobo; Felisbina Queiroga

    2015-01-01

    In this study 80 malignant CMT were submitted to immunohistochemical detection of CD3, c-kit, VEGF, and CD31, together with clinicopathological parameters of tumor aggressiveness. CD3+ T-cells and c-kit overexpression revealed a positive correlation with VEGF (r = 0.503, P < 0.0001; r = 0.284, P = 0.023 for CD3 and c-kit, resp.) and CD31 (r = 0.654, P < 0.0001; r = 0.365, P = 0.003 for CD3 and c-kit, resp.). A significant association (P = 0.039) and a positive correlation (r = 0.263, P = 0.03...

  6. MiR-24 promotes the survival of hematopoietic cells.

    Directory of Open Access Journals (Sweden)

    Tan Nguyen

    Full Text Available The microRNA, miR-24, inhibits B cell development and promotes myeloid development of hematopoietic progenitors. Differential regulation of cell survival in myeloid and lymphoid cells by miR-24 may explain how miR-24's affects hematopoietic progenitors. MiR-24 is reported to regulate apoptosis, either positively or negatively depending on cell context. However, no role for miR-24 in regulating cell death has been previously described in blood cells. To examine miR-24's effect on survival, we expressed miR-24 via retrovirus in hematopoietic cells and induced cell death with cytokine or serum withdrawal. We observed that miR-24 enhanced survival of myeloid and B cell lines as well as primary hematopoietic cells. Additionally, antagonizing miR-24 with shRNA in hematopoietic cells made them more sensitive to apoptotic stimuli, suggesting miR-24 functions normally to promote blood cell survival. Since we did not observe preferential protection of myeloid over B cells, miR-24's pro-survival effect does not explain its promotion of myelopoiesis. Moreover, expression of pro-survival protein, Bcl-xL, did not mimic miR-24's impact on cellular differentiation, further supporting this conclusion. Our results indicate that miR-24 is a critical regulator of hematopoietic cell survival. This observation has implications for leukemogenesis. Several miRNAs that regulate apoptosis have been shown to function as either tumor suppressors or oncogenes during leukemogenesis. MiR-24 is expressed highly in primary acute myelogenous leukemia, suggesting that its pro-survival activity could contribute to the transformation of hematopoietic cells.

  7. Apoptose no tumor venéreo transmissível canino: características morfológicas e evidenciação bioquímica Apoptosis in the canine transmissible venereal tumor: morphological features and biochemical evidence

    Directory of Open Access Journals (Sweden)

    F.G.A. Santos

    2001-10-01

    Full Text Available Fragmentos de tumor venéreo transmissível canino (TVTC de ocorrência natural, com localização genital, foram obtidos de cinco animais, machos, adultos, sem raça definida. "Imprints" da superfície de corte em lâmina de microscopia foram fixadas em metanol, coradas pelo Giemsa e submetidas à avaliação citológica. Os fragmentos foram fixados e processados rotineiramente para inclusão em parafina e coloração com HE e Shorr, para confirmação histológica do tumor e identificação da apoptose. Outros fragmentos foram envolvidos com papel alumínio e acondicionados dentro de frascos de vidro em gelo seco, para serem processados no mesmo dia, visando à extração de DNA e eletroforese em gel de agarose. Análises cito e histológica do TVTC mostraram a distribuição e o padrão celular e tecidual característicos dessa neoplasia, sobressaindo-se a presença de vacúolos claros, bem definidos no citoplasma à análise citológica. Pela coloração com Shorr pôde-se identificar células retraídas, com aumento da acidofilia citoplasmática e condensação da cromatina nuclear, às vezes com fragmentação do núcleo e das células, caracterizando apoptose. A coloração pelo Shorr mostrou ser mais eficiente na distinção de células apoptóticas do que a coloração por HE. A eletroforese de DNA em gel de agarose demonstrou a fragmentação internucleossômica do genoma, que pôde ser reconhecida pelo clássico "padrão em escada".Fragments of canine transmissible venereal tumors, from natural cases and genital localization, were obtained from five adult male mongrel dogs. Imprints of the tumors were fixed, stained by Giemsa and submitted to cytological analysis to confirm the diagnosis. Representative samples of the tumoral tissue were fixed, embedded in paraffin and processed routinely for microscopic examination. Sections were stained with hematoxylin - eosin and Shorr. Another set of fragments was packed and maintained in dry ice

  8. Functions of TET Proteins in Hematopoietic Transformation.

    Science.gov (United States)

    Han, Jae-A; An, Jungeun; Ko, Myunggon

    2015-11-01

    DNA methylation is a well-characterized epigenetic modification that plays central roles in mammalian development, genomic imprinting, X-chromosome inactivation and silencing of retrotransposon elements. Aberrant DNA methylation pattern is a characteristic feature of cancers and associated with abnormal expression of oncogenes, tumor suppressor genes or repair genes. Ten-eleven-translocation (TET) proteins are recently characterized dioxygenases that catalyze progressive oxidation of 5-methylcytosine to produce 5-hydroxymethylcytosine and further oxidized derivatives. These oxidized methylcytosines not only potentiate DNA demethylation but also behave as independent epigenetic modifications per se. The expression or activity of TET proteins and DNA hydroxymethylation are highly dysregulated in a wide range of cancers including hematologic and non-hematologic malignancies, and accumulating evidence points TET proteins as a novel tumor suppressor in cancers. Here we review DNA demethylation-dependent and -independent functions of TET proteins. We also describe diverse TET loss-of-function mutations that are recurrently found in myeloid and lymphoid malignancies and their potential roles in hematopoietic transformation. We discuss consequences of the deficiency of individual Tet genes and potential compensation between different Tet members in mice. Possible mechanisms underlying facilitated oncogenic transformation of TET-deficient hematopoietic cells are also described. Lastly, we address non-mutational mechanisms that lead to suppression or inactivation of TET proteins in cancers. Strategies to restore normal 5mC oxidation status in cancers by targeting TET proteins may provide new avenues to expedite the development of promising anti-cancer agents.

  9. A pRb-responsive, RGD-modified, and Hyaluronidase-armed Canine Oncolytic Adenovirus for Application in Veterinary Oncology

    OpenAIRE

    Laborda, Eduardo; Puig-Saus, Cristina; Rodriguez-García, Alba; Moreno, Rafael; Cascalló, Manel; Pastor, Josep; Alemany, Ramon

    2014-01-01

    Human and canine cancer share similarities such as genetic and molecular aspects, biological complexity, tumor epidemiology, and targeted therapeutic treatment. Lack of good animal models for human adenovirotherapy has spurred the use of canine adenovirus 2-based oncolytic viruses. We have constructed a canine oncolytic virus that mimics the characteristics of our previously published human adenovirus ICOVIR17: expression of E1a controlled by E2F sites, deletion of the pRb-binding site of E1a...

  10. Expressão dos filamentos intermediários no diagnóstico dos tumores mamários de cadelas Expression of intermediate filaments in canine mammary tumors diagnosis

    OpenAIRE

    D.A.P.C. Zuccari; Santana, A. E.; N.S. Rocha

    2002-01-01

    Foram utilizados anticorpos monoclonais para marcação imunoistoquímica dos tecidos tumorais e obtenção de informações sobre a histogênese dos tumores mamários utilizando-se anti-citoqueratinas para marcação de células epiteliais, e anti-actina e anti-vimentina para células mioepiteliais. O procedimento imunoistoquímico mostrou-se esclarecedor com relação à histogênese dos tumores mamários, confirmando a marcação de células epiteliais com as citoqueratinas que perdem sua expressão na transform...

  11. Clinical utility of a life quality score in dogs with canine transmissible venereal tumor treated by vincristine chemotherapy Utilidade clínica de escala de qualidade de vida durante o tratamento quimioterápico de cães com tumor venéreo transmissível canino (TVTC com vincristina

    Directory of Open Access Journals (Sweden)

    M.L. Valladão

    2010-10-01

    Full Text Available The clinical utility of a life quality score during vincristine chemotherapy of dogs with canine transmissible venereal tumor (CTVT was investigated using 93 tumor-bearing dogs in this prospective study. At diagnosis, clinical data and the performance status were evaluated according to a modified Karnofsky score (CKS adapted for dogs. The animals were treated with vincristine sulphate (0.025mg/kg at weekly intervals until the tumor had macroscopically disappeared. The time until the first adverse event and death were recorded. In a pilot study, CKS revealed a high inter-observer concordance (kappa=0.735; weighted kappa=0.835. CKS permitted a detailed monitoring of adverse effects during therapy. Cox regressions showed that low performance score and reduced body weight were independent predictive factors for death during chemotherapy. The modified Karnofsky performance score is a simple and reproducible clinical instrument, able to estimate patient outcome after treatment of CTVT.Investigou-se a utilidade clínica de uma escala de qualidade de vida durante o tratamento quimioterápico de cães com tumor venéreo transmissível canino (TVTC em 93 animais com TVTC que compuseram este estudo prospectivo. Ao diagnóstico, foram avaliados os dados clínicos e o escore de qualidade de vida adaptado para cães (CKS. Os animais foram tratados com sulfato de vincristina (0.025mg/kg semanalmente até o desaparecimento macroscópico do tumor. Foram anotados o tempo até o aparecimento do primeiro evento adverso e a morte. Em estudo piloto do CKS, alta concordância entre os observadores foi demonstrada (kappa = 0.735; weighted kappa = 0.835. O CKS permitiu um detalhado monitoramento dos eventos adversos durante a terapia. A regressão Cox multivariada demonstrou que o baixo escore de qualidade de vida e o reduzido peso corporal foram fatores preditivos independentes para o óbito durante a quimioterapia. A escala modificada de Karnofsky é um instrumento cl

  12. Vaccines for Canine Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Faeze Foroughi-Parvar

    2014-01-01

    Full Text Available Leishmania infantum is the obligatory intracellular parasite of mammalian macrophages and causes zoonotic visceral leishmaniasis (ZVL. The presence of infected dogs as the main reservoir host of ZVL is regarded as the most important potential risk for human infection. Thus the prevention of canine visceral leishmaniasis (CVL is essential to stop the current increase of the Mediterranean visceral leishmaniasis. Recently considerable advances in achieving protective immunization of dogs and several important attempts for achieving an effective vaccine against CVL lead to attracting the scientists trust in its important role for eradication of ZVL. This paper highlights the recent advances in vaccination against canine visceral leishmaniasis from 2007 until now.

  13. 应用分子靶点药物治疗犬肥大细胞瘤的研究进展%Progress on Application of Molecular Target Drugs in Treatments of Canine Mast Cell Tumors

    Institute of Scientific and Technical Information of China (English)

    李格宾; 杨紫嫣; 林珈好; 夏兆飞

    2016-01-01

    犬肥大细胞瘤因其恶性率和转移率都较高,并且常规化疗药物副作用较强,患犬生存期和生存质量显著下降,因此急需新型的药物进行治疗。近几年,治疗肿瘤的分子靶点药物凭借其疗效好、副作用低的特点,受到越来越广泛的关注,特别是在治疗犬肥大细胞瘤的应用中效果显著。论文重点介绍了欧美小动物临床最常用的伊马替尼、托赛拉尼、马赛替尼这3种以异常 KIT 为靶点的药物及其药物作用机理及药效,最后介绍了由 c-kit 基因二次突变所导致的耐药问题及其预防措施,期望能对我国小动物临床医师和科研工作者有所启发。%Mast cell tumors (MCT)have the high metastatic and mortality rate.Moreover,the convention-al chemotherapy drugs have many unpleasant side effects.As such,dogs with anaplastic MCT remain a frustrating undertaking of survival time and quality of life.Therefore,it is necessary to have better under-standing of novel,effective drugs for control of MCT.With the dramatically development of molecule biol-ogy in oncology field,molecular target drugs have been aroused general concern because of their great effect and low side-effect.Especially,molecular target drugs have attained remarkably effect of canine MCT treatment.In the present paper,we emphasized the mechanism and effect of three drugs (Imatinib, Toceranib and Masitinib)which are the most commonly used in America and Europe and targeted to the c-kit gene.At last we showed the drug resistance and preventive measure caused by second mutation of c-kit gene.We hope these could provide references to scientific researchers and small animal clinical practitioners in China.

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

    International Nuclear Information System (INIS)

    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

  15. Vaccines for canine leishmaniasis

    Directory of Open Access Journals (Sweden)

    Clarisa B. Palatnik-De-Sousa

    2012-04-01

    Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans

  16. Oncolytic virotherapy in veterinary medicine: current status and future prospects for canine patients

    Directory of Open Access Journals (Sweden)

    Patil Sandeep S

    2012-01-01

    Full Text Available Abstract Oncolytic viruses refer to those that are able to eliminate malignancies by direct targeting and lysis of cancer cells, leaving non-cancerous tissues unharmed. Several oncolytic viruses including adenovirus strains, canine distemper virus and vaccinia virus strains have been used for canine cancer therapy in preclinical studies. However, in contrast to human studies, clinical trials with oncolytic viruses for canine cancer patients have not been reported. An 'ideal' virus has yet to be identified. This review is focused on the prospective use of oncolytic viruses in the treatment of canine tumors - a knowledge that will undoubtedly contribute to the development of oncolytic viral agents for canine cancer therapy in the future.

  17. The canine vomeronasal organ.

    OpenAIRE

    Adams, D. R.; Wiekamp, M D

    1984-01-01

    The vomeronasal organ was studied in mature dogs with the optical, transmission electron, and scanning electron microscopes. The canine vomeronasal complex is structurally well developed. Large blood vessels are present deep to both the lateral, 'non-receptor' and medial, 'receptor' epithelia. In addition to the unmyelinated vomeronasal nerves in the lamina propria deep to the 'receptor' epithelium, numerous nerves containing both myelinated and unmyelinated fibres are present deep to the 'no...

  18. Characterizing the human hematopoietic CDome

    DEFF Research Database (Denmark)

    Barnkob, Mike Stein; Simon, Christian; Olsen, Lars Rønn

    2014-01-01

    In this study, we performed extensive semi-automated data collection from the primary and secondary literature in an effort to characterize the expression of all membrane proteins within the CD scheme on hematopoietic cells. Utilizing over 6000 data points across 305 CD molecules on 206 cell types......, we seek to give a preliminary characterization of the "human hematopoietic CDome." We encountered severe gaps in the knowledge of CD protein expression, mostly resulting from incomplete and unstructured data generation, which we argue inhibit both basic research as well as therapies seeking to target...

  19. Cellular and Phenotypic Characterization of Canine Osteosarcoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Marie E. Legare, Jamie Bush, Amanda K. Ashley, Taka Kato, William H. Hanneman

    2011-01-01

    Full Text Available Canine and human osteosarcoma (OSA have many similarities, with the majority of reported cases occurring in the appendicular skeleton, gender predominance noted, high rate of metastasis at the time of presentation, and a lack of known etiology for this devastating disease. Due to poor understanding of the molecular mechanisms underlying OSA, we have characterized seven different OSA canine cell lines: Abrams, D17, Grey, Hughes, Ingles, Jarques, and Marisco and compared them to U2, a human OSA cell line, for the following parameters: morphology, growth, contact inhibition, migrational tendencies, alkaline phosphatase staining, heterologous tumor growth, double-strand DNA breaks, and oxidative damage. All results demonstrated the positive characteristics of the Abrams cell line for use in future studies of OSA. Of particular interest, the robust growth of a subcutaneous tumor and rapid pulmonary metastasis of the Abrams cell line in an immunocompromised mouse shows incredible potential for the future use of Abrams as a canine OSA model. Further investigations utilizing a canine cell model of OSA, such as Abrams, will be invaluable to understanding the molecular events underlying OSA, pharmaceutical inhibition of metastasis, and eventual prevention of this devastating disease.

  20. Preclinical evaluation of oncolytic vaccinia virus for therapy of canine soft tissue sarcoma.

    Directory of Open Access Journals (Sweden)

    Ivaylo Gentschev

    Full Text Available Virotherapy using oncolytic vaccinia virus (VACV strains is one promising new strategy for canine cancer therapy. In this study we describe the establishment of an in vivo model of canine soft tissue sarcoma (CSTS using the new isolated cell line STSA-1 and the analysis of the virus-mediated oncolytic and immunological effects of two different Lister VACV LIVP1.1.1 and GLV-1h68 strains against CSTS. Cell culture data demonstrated that both tested VACV strains efficiently infected and destroyed cells of the canine soft tissue sarcoma line STSA-1. In addition, in our new canine sarcoma tumor xenograft mouse model, systemic administration of LIVP1.1.1 or GLV-1h68 viruses led to significant inhibition of tumor growth compared to control mice. Furthermore, LIVP1.1.1 mediated therapy resulted in almost complete tumor regression and resulted in long-term survival of sarcoma-bearing mice. The replication of the tested VACV strains in tumor tissues led to strong oncolytic effects accompanied by an intense intratumoral infiltration of host immune cells, mainly neutrophils. These findings suggest that the direct viral oncolysis of tumor cells and the virus-dependent activation of tumor-associated host immune cells could be crucial parts of anti-tumor mechanism in STSA-1 xenografts. In summary, the data showed that both tested vaccinia virus strains and especially LIVP1.1.1 have great potential for effective treatment of CSTS.

  1. Polycomb-group proteins in hematopoietic stem cell regulation and hematopoietic neoplasms.

    Science.gov (United States)

    Radulović, V; de Haan, G; Klauke, K

    2013-03-01

    The equilibrium between self-renewal and differentiation of hematopoietic stem cells is regulated by epigenetic mechanisms. In particular, Polycomb-group (PcG) proteins have been shown to be involved in this process by repressing genes involved in cell-cycle regulation and differentiation. PcGs are histone modifiers that reside in two multi-protein complexes: Polycomb Repressive Complex 1 and 2 (PRC1 and PRC2). The existence of multiple orthologs for each Polycomb gene allows the formation of a multitude of distinct PRC1 and PRC2 sub-complexes. Changes in the expression of individual PcG genes are likely to cause perturbations in the composition of the PRC, which affect PRC enzymatic activity and target selectivity. An interesting recent development is that aberrant expression of, and mutations in, PcG genes have been shown to occur in hematopoietic neoplasms, where they display both tumor-suppressor and oncogenic activities. We therefore comprehensively reviewed the latest research on the role of PcG genes in normal and malignant blood cell development. We conclude that future research to elucidate the compositional changes of the PRCs and methods to intervene in PRC assembly will be of great therapeutic relevance to combat hematological malignancies.

  2. Hematopoietic expression of oncogenic BRAF promotes aberrant growth of monocyte-lineage cells resistant to PLX4720

    OpenAIRE

    Kamata, Tamihiro; Dankort, David; Kang, Jing; Giblett, Susan; Pritchard, Catrin A.; McMahon, Martin; Leavitt, Andrew D.

    2013-01-01

    Mutational activation of BRAF leading to expression of the BRAFV600E oncoprotein was recently identified in a high percentage of specific hematopoietic neoplasms in monocyte/histiocyte and mature B-cell lineages. Although BRAFV600E is a driver oncoprotein and pharmacological target in solid tumors such as melanoma, lung and thyroid cancer, it remains unknown whether BRAFV600E is an appropriate therapeutic target in hematopoietic neoplasms. To address this critical question, we generated a mou...

  3. Classificação da Organização Mundial da Saúde para os tumores dos tecidos hematopoético e linfoide, 4ª edição, 2008: principais modificações introduzidas em relação à 3ª edição, 2001 World Health Organization classification of tumors of hematopoietic and lymphoid tissues, 4th edition, 2008: major changes from the 3rd edition, 2001

    Directory of Open Access Journals (Sweden)

    Maria Claudia Nogueira Zerbini

    2011-02-01

    Full Text Available A Classificação da Organização Mundial da Saúde (OMS para os tumores do tecido hematopoético e linfoide (4ª edição, 2008¹ representa uma atualização da 3ª edição, 2001². Apresentamos a seguir um resumo dessas alterações nos grupos das doenças mieloproliferativas, mileodisplásicas, leucemias mieloides agudas, neoplasias de células precursoras B e T, e neoplasias de células B, T e NK maduras. O entendimento das alterações genético-moleculares e os resultados alcançados com propostas terapêuticas inovadoras nesses grupos de doenças demandam constante reavaliação de sua classificação, justificando as alterações importantes aqui discutidas1,3-5.The World Health Organization (WHO Classification of tumors of hematopoietic and lymphoid tissues (4th edition, 2008¹ presents an updated version of the 3rd edition published in 2001². A summary of these changes relates to the groups of chronic myeloproliferative disorders, myelodisplasia, acute myeloid leukemias, neoplasms of precursor B and T cells and neoplasms derived of mature B, T and NK cells. A better understanding of molecular genetic changes and results achieved with innovative therapeutic approaches in these groups of diseases requires constant reassessment of the classifications, supporting the major changes discussed here, including interesting comments from literature1, 3-5.

  4. Multi-drug resistance in a canine lymphoid cell line due to increased P-glycoprotein expression, a potential model for drug-resistant canine lymphoma

    NARCIS (Netherlands)

    Zandvliet, M; Teske, E; Schrickx, J A

    2014-01-01

    Canine lymphoma is routinely treated with a doxorubicin-based multidrug chemotherapy protocol, and although treatment is initially successful, tumor recurrence is common and associated with therapy resistance. Active efflux of chemotherapeutic agents by transporter proteins of the ATP-Binding Casset

  5. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Science.gov (United States)

    2010-01-01

    ... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing cell... hepatitis, the test is inconclusive and may be repeated. (B) If at least 19 of the 20 vaccinates do...

  6. Characterization and Comparison of Cancer Stem Cells in Human and Canine Glioma Cell Lines

    Directory of Open Access Journals (Sweden)

    Thomas Clements

    2012-01-01

    Full Text Available Gliomas are among the most common and malignantforms of primary brain tumors that occur naturally inhumans. They represent about 33% of brain tumorsand 80% of malignant brain tumors. Gliomas alsospontaneously arise in specific breeds in the canine family.Canine gliomas are histologically similar to human gliomaand have similar presentation and response to treatmentin the clinic. A comparison of canine and human gliomascould prove to be invaluable, because the acceptedrodent model has limitations when testing therapies andidentifying targets. Our goal is to obtain global proteinexpression and metabolic profiles of different classificationand grades of human and canine glioma, in order toidentify and compare the tumor survival strategies in bothsystems. Toward this end, we harvested and cultured cellsfrom a naturally occurring grade-3 oligodendrogliomatumor that was isolated from a canine patient at the PurdueUniversity Veterinary Teaching Hospital. Similar to cellsfrom human glioma, these cells formed neurosphereswhen cultured in serum free media in the presence of FGFand EGF. The cells were also sensitive to plating densityand oxygen concentrations.This work was supported by the National Institutes ofHealth, National Cancer Institute R25CA128770 CancerPrevention Internship Program administered by theOncological Sciences Center and the Discovery LearningResearch Center at Purdue University. This work wasalso supported by Showalter Research Foundation and aCollege of Technology Seed Grant.

  7. Pharmacologic inhibition of MEK signaling prevents growth of canine hemangiosarcoma

    Science.gov (United States)

    Andersen, Nicholas J.; Nickoloff, Brian J.; Dykema, Karl J.; Boguslawski, Elissa A.; Krivochenitser, Roman I.; Froman, Roe E.; Dawes, Michelle J.; Baker, Laurence H.; Thomas, Dafydd G.; Kamstock, Debra A.; Kitchell, Barbara E.; Furge, Kyle A.; Duesbery, Nicholas S.

    2013-01-01

    Angiosarcoma (AS) is a rare neoplasm of endothelial origin that has limited treatment options and poor five-year survival. As a model for human AS, we studied primary cells and tumorgrafts derived from canine hemangiosarcoma (HSA), which is also an endothelial malignancy with similar presentation and histology. Primary cells isolated from HSA showed constitutive ERK activation. The MEK inhibitor CI-1040 reduced ERK activation and the viability of primary cells derived from visceral, cutaneous, and cardiac HSA in vitro. HSA-derived primary cells were also sensitive to sorafenib, an inhibitor of B-Raf and multi-receptor tyrosine kinases. In vivo, CI-1040 or PD0325901 decreased the growth of cutaneous cell-derived xenografts and cardiac-derived tumorgrafts. Sorafenib decreased tumor size in both in vivo models, although cardiac tumorgrafts were more sensitive. In human AS, we noted that 50% of tumors stained positively for phosphorylated ERK1/2 and that the expression of several MEK-responsive transcription factors was up-regulated. Our data showed that MEK signaling is essential for the growth of HSA in vitro and in vivo and provided evidence that the same pathways are activated in human AS. This indicates that MEK inhibitors may form part of an effective therapeutic strategy for the treatment of canine HSA or human AS, and it highlights the utility of spontaneous canine cancers as a model of human disease. PMID:23804705

  8. Analysis of EGFR and HER-2 expressions in ductal carcinomas in situ in canine mammary glands

    Directory of Open Access Journals (Sweden)

    I.L.D. Silva

    2014-06-01

    Full Text Available Biomolecular evidence has shown that ductal carcinoma in situ (DCIS may develop into invasive carcinoma of the canine mammary gland, and mutations in proto-oncogenes HER2 and EGFR; two members of the family of epidermal growth factor receptors, may be involved in this process. The purpose of this study was the characterization of the immunohistochemical expression of the EGFR and HER2 proteins in the process of neoplastic transformation, supposedly present in ductal carcinomas in situ in canine mammary glands. Fifteen cases of DCIS were evaluated, with a higher expression of HER2 and EGFR being observed in low-grade carcinomas when compared with high-grade neoplasms, and with a high positive statistical correlation in the latter. Results suggest that aggressive tumors tend to lose the expression of EGFR and HER2 simultaneously. The loss of the expression of these markers may be related to the process of neoplastic progression in canine mammary tumors.

  9. Histocompatibility and Hematopoietic Transplantation in the Zebrafish

    Directory of Open Access Journals (Sweden)

    Jill L. O. de Jong

    2012-01-01

    Full Text Available The zebrafish has proven to be an excellent model for human disease, particularly hematopoietic diseases, since these fish make similar types of blood cells as humans and other mammals. The genetic program that regulates the development and differentiation of hematopoietic cells is highly conserved. Hematopoietic stem cells (HSCs are the source of all the blood cells needed by an organism during its lifetime. Identifying an HSC requires a functional assay, namely, a transplantation assay consisting of multilineage engraftment of a recipient and subsequent serial transplant recipients. In the past decade, several types of hematopoietic transplant assays have been developed in the zebrafish. An understanding of the major histocompatibility complex (MHC genes in the zebrafish has lagged behind transplantation experiments, limiting the ability to perform unbiased competitive transplantation assays. This paper summarizes the different hematopoietic transplantation experiments performed in the zebrafish, both with and without immunologic matching, and discusses future directions for this powerful experimental model of human blood diseases.

  10. The anti-canine distemper virus activities of ex vivo-expanded canine natural killer cells.

    Science.gov (United States)

    Park, Ji-Yun; Shin, Dong-Jun; Lee, Soo-Hyeon; Lee, Je-Jung; Suh, Guk-Hyun; Cho, Duck; Kim, Sang-Ki

    2015-04-17

    Natural killer (NK) cells play critical roles in induction of antiviral effects against various viruses of humans and animals. However, few data on NK cell activities during canine distemper virus (CDV) infections are available. Recently, we established a culture system allowing activation and expansion of canine non-B, non-T, large granular NK lymphocytes from PBMCs of normal dogs. In the present study, we explored the ability of such expanded NK cells to inhibit CDV infection in vitro. Cultured CD3-CD5-CD21- NK cells produced large amounts of IFN-γ, exhibited highly upregulated expression of mRNAs encoding NK-cell-associated receptors, and demonstrated strong natural killing activity against canine tumor cells. Although the expanded NK cells were dose-dependently cytotoxic to both normal and CDV-infected Vero cells, CDV infection rendered Vero cells more susceptible to NK cells. Pretreatment with anti-CDV serum from hyperimmunized dogs enhanced the antibody-dependent cellular cytotoxicity (ADCC) of NK cells against CDV-infected Vero cells. The culture supernatants of NK cells, added before or after infection, dose-dependently inhibited both CDV replication and development of CDV-induced cytopathic effects (CPEs) in Vero cells. Anti-IFN-γ antibody neutralized the inhibitory effects of NK cell culture supernatants on CDV replication and CPE induction in Vero cells. Such results emphasize the potential significance of NK cells in controlling CDV infection, and indicate that NK cells may play roles both during CDV infection and in combating such infections, under certain conditions. PMID:25680810

  11. Imaging of complications from hematopoietic stem cell transplant

    Directory of Open Access Journals (Sweden)

    Tarun Pandey

    2014-01-01

    Full Text Available Stem cell transplant has been the focus of clinical research for a long time given its potential to treat several incurable diseases like hematological malignancies, diabetes mellitus, and neuro-degenerative disorders like Parkinson disease. Hematopoietic stem cell transplantation (HSCT is the oldest and most widely used technique of stem cell transplant. HSCT has not only been used to treat hematological disorders including hematological malignancies, but has also been found useful in treamtent of genetic, immunological, and solid tumors like neuroblastoma, lymphoma, and germ cell tumors. In spite of the rapid advances in stem cell technology, success rate with this technique has not been universal and many complications have also been seen with this form of therapy. The key to a successful HSCT therapy lies in early diagnosis and effective management of complications associated with this treatment. Our article aims to review the role of imaging in diagnosis and management of stem cell transplant complications associated with HSCT.

  12. Anti-influenza neuraminidase inhibitor oseltamivir phosphate induces canine mammary cancer cell aggressiveness.

    Science.gov (United States)

    de Oliveira, Joana T; Santos, Ana L; Gomes, Catarina; Barros, Rita; Ribeiro, Cláudia; Mendes, Nuno; de Matos, Augusto J; Vasconcelos, M Helena; Oliveira, Maria José; Reis, Celso A; Gärtner, Fátima

    2015-01-01

    Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x) expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness. PMID:25850034

  13. Anti-influenza neuraminidase inhibitor oseltamivir phosphate induces canine mammary cancer cell aggressiveness.

    Directory of Open Access Journals (Sweden)

    Joana T de Oliveira

    Full Text Available Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness.

  14. The role of the embryonic microenvironment in hematopoietic cell development

    NARCIS (Netherlands)

    E. Haak (Esther)

    2007-01-01

    textabstractThe adult hematopoietic system is comprised of a hierarchy of cells with the hematopoietic stem cell (HSC) at its foundation. HSCs give rise to progenitors that differentiate into mature hematopoietic cells, which perform the physiological functions of the hematopoietic system. The matur

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

    Science.gov (United States)

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

    2015-01-01

    In the present study, 13 clinical cases of canine mammary adenocarcinoma were evaluated in order to understand the effect of Tarantula cubensis extract (TCE) on tumor tissue. Punch biopsies were taken from the tumors before treatment with TCE. Subcutaneous injections of TCE were administered three times at weekly intervals (3 mL per dog). Between days 7 and 10 after the third injection, the tumor masses were extirpated by complete unilateral mastectomy. Pre- and post-treatment tumor tissues were immunohistochemically assessed. The expression of B-cell lymphoma 2 (Bcl-2) was found to be higher in pre-treatment compared to post-treatment tissues (p 0.05). The apoptotic index was determined to be low before treatment and increased during treatment. These results suggest that TCE may be effective for controlling the local growth of canine mammary adenocarcinoma by regulating apoptosis. PMID:25549212

  16. Ultra-estrutura dos mastócitos de diferentes tipos histológicos de mastocitoma em cães Mast cell ultrastructure in different types of canine mast cell tumor

    Directory of Open Access Journals (Sweden)

    F.A.R. Sueiro

    2002-06-01

    Full Text Available Este trabalho teve por objetivo estudar as diferenças ultraestruturais de mastócitos neoplásicos de diferentes tipos histológicos de mastocitoma em cães, usando microscopia eletrônica de transmissão Os resultados mostraram que o núcleo e os grânulos citoplasmáticos são as estruturas mais indicadas para se avaliar o grau de anaplasia celular e o estádio de indiferenciação do tumor.The objective of this work was study the ultrastructural differences among the different histologic types of mast cell tumors in dogs collected in vivo. The ultrastructural analyses showed that the nuclei and cytoplasmic granules characteristics are the best structures to be appointed on evaluating the undifferentiation stage of this tumor.

  17. Molecular mechanisms underlying adhesion and migration of hematopoietic stem cells

    OpenAIRE

    Sahin, Aysegul Ocal; Buitenhuis, Miranda

    2012-01-01

    Hematopoietic stem cell transplantation is the most powerful treatment modality for a large number of hematopoietic malignancies, including leukemia. Successful hematopoietic recovery after transplantation depends on homing of hematopoietic stem cells to the bone marrow and subsequent lodging of those cells in specific niches in the bone marrow. Migration of hematopoietic stem cells to the bone marrow is a highly regulated process that requires correct regulation of the expression and activit...

  18. Canine Oral Eosinophilic Granuloma Treated with Electrochemotherapy

    Directory of Open Access Journals (Sweden)

    Matías Nicolás Tellado

    2014-01-01

    Full Text Available A case of a canine oral eosinophilic granuloma in a 14-year-old female crossbred is described. The dog was presented with a history of ptyalism, halitosis, local pain, decreased appetite, and blood staining noted on food and water bowls. Clinical, hematologic, and biochemical examinations, abdominal ultrasonography, and 3-view chest radiographs were performed, and no metastases were found. Histopathologic examination of two 6 mm punch biopsies from the oral lesion revealed the presence of eosinophilic granulomatous lesions in the submucosa. After treatment with corticosteroids and wide spectrum antibiotics no significant changes in clinical signs and lesion size were observed. Electrochemotherapy (ECT, a novel tumor treatment routinely used for cutaneous and subcutaneous tumors in human patients in the European Union since 2006, was used to treat the eosinophilic granuloma. The procedure was performed under general anesthesia, followed by intravenous administration of bleomycin. Six weeks after treatment a complete response with disappearance of the mass and improvement of clinical signs were observed.

  19. Canine Butterfly Glioblastomas: A Neuroradiological Review

    Science.gov (United States)

    Rossmeisl, John H.; Clapp, Kemba; Pancotto, Theresa E.; Emch, Samantha; Robertson, John L.; Debinski, Waldemar

    2016-01-01

    In humans, high-grade gliomas may infiltrate across the corpus callosum resulting in bihemispheric lesions that may have symmetrical, winged-like appearances. This particular tumor manifestation has been coined a “butterfly” glioma (BG). While canine and human gliomas share many neuroradiological and pathological features, the BG morphology has not been previously reported in dogs. Here, we describe the magnetic resonance imaging (MRI) characteristics of BG in three dogs and review the potential differential diagnoses based on neuroimaging findings. All dogs presented for generalized seizures and interictal neurological deficits referable to multifocal or diffuse forebrain disease. MRI examinations revealed asymmetrical (2/3) or symmetrical (1/3), bihemispheric intra-axial mass lesions that predominantly affected the frontoparietal lobes that were associated with extensive perilesional edema, and involvement of the corpus callosum. The masses displayed heterogeneous T1, T2, and fluid-attenuated inversion recovery signal intensities, variable contrast enhancement (2/3), and mass effect. All tumors demonstrated classical histopathological features of glioblastoma multiforme (GBM), including glial cell pseudopalisading, serpentine necrosis, microvascular proliferation as well as invasion of the corpus callosum by neoplastic astrocytes. Although rare, GBM should be considered a differential diagnosis in dogs with an MRI evidence of asymmetric or symmetric bilateral, intra-axial cerebral mass lesions with signal characteristics compatible with glioma.

  20. CANINE BUTTERFLY GLIOBLASTOMAS: A NEURORADIOLOGICAL REVIEW

    Directory of Open Access Journals (Sweden)

    John Henry Rossmeisl

    2016-05-01

    Full Text Available In humans, high-grade gliomas may infiltrate across the corpus callosum resulting in bihemispheric lesions that may have symmetrical, winged-like appearances. This particular tumor manifestation has been coined a ‘butterfly’ glioma (BG. While canine and human gliomas share many neuroradiological and pathological features, the BG morphology has not been previously reported in dogs. Here we describe the magnetic resonance imaging (MRI characteristics of BG in three dogs, and review the potential differential diagnoses based on neuroimaging findings. All dogs presented with generalized seizures and interictal neurological deficits referable to multifocal or diffuse forebrain disease. MRI examinations revealed asymmetrical (2/3 or symmetrical (1/3, bihemispheric intra-axial mass lesions that predominantly affected the frontoparietal lobes and associated with extensive perilesional edema, and involvement of the corpus callosum. The masses displayed heterogeneous T1, T2, and FLAIR signal intensities, variable contrast enhancement (2/3, and mass effect. All tumors demonstrated classical histopathological features of glioblastoma (GBM including glial cell pseudopalisading, serpentine necrosis, microvascular proliferation, as well as invasion of the corpus callosum by neoplastic astrocytes. Although rare, GBM should be considered a differential diagnosis in dogs with MRI evidence of asymmetric or symmetric bilateral, intra-axial cerebral mass lesions with signal characteristics compatible with glioma.

  1. Current developments in canine genetics.

    Science.gov (United States)

    Marschall, Yvonne; Distl, Ottmar

    2010-01-01

    In recent years, canine genetics had made huge progress. In 1999 the first complete karyotype and ideogram of the dog was published. Several linkage and RH maps followed. Using these maps, sets of microsatellite markers for whole genome scans were compiled. In 2003 the sequencing of the DNA of a female Boxer began. Now the second version of the dog genome assembly has been put online, and recently, a microchip SNP array became available. Parallel to these developments, some causal mutations for different traits have been identified. Most of the identified mutations were responsible for monogenic canine hereditary diseases. With the tools available now, it is possible to use the advantages of the population structure of the various dog breeds to unravel complex genetic traits. Furthermore, the dog is a suitable model for the research of a large number of human hereditary diseases and particularly for cancer genetics, heart and neurodegenerative diseases. There are some examples where it was possible to benefit from the knowledge of canine genetics for human research. The search for quantitative trait loci (QTL), the testing of candidate genes and genome-wide association studies can now be performed in dogs. QTL for skeletal size variations and for canine hip dysplasia have been already identified and for these complex traits the responsible genes and their possible interactions can now be identified. PMID:20690545

  2. Prognostic markers of canine pyometra

    OpenAIRE

    M.C. Sant'Anna; L.G.P. Giordano; K.K.M.C. Flaiban; Muller, E.E.; M.I.M. Martins

    2014-01-01

    The pyometra is a disease that affects middle age and elderly female dogs during diestrus. Hormonal, microbiological, biochemical and hematological aspects are well described. However, few studies have evaluated the role of each in the prognosis of canine pyometra. The aim of this study was to identify markers associated with clinical worsening of dogs with pyometra. We prospectively evaluated 80 dogs with pyometra tre...

  3. Surgical innovations in canine gonadectomy

    NARCIS (Netherlands)

    Van Goethem, Bart

    2016-01-01

    In this thesis some recent technological developments in human surgery are evaluated for their potential use in veterinary medicine by introducing them as surgical innovations for canine gonadectomy. Barbed sutures achieve wound apposition without surgical knot tying and thus avoid knot-associated n

  4. PARASITIC INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Isidro Jarque

    2016-07-01

    Full Text Available Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However, they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients.

  5. Parasitic Infections in Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Jarque, Isidro; Salavert, Miguel; Pemán, Javier

    2016-01-01

    Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients. PMID:27413527

  6. Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model

    Energy Technology Data Exchange (ETDEWEB)

    Kane, Jonathan [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States); Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Krueger, Sarah A.; Dilworth, Joshua T.; Torma, John T.; Wilson, George D.; Marples, Brian [Radiation Oncology, William Beaumont Health System, Royal Oak, Michigan (United States); Madlambayan, Gerard J., E-mail: madlamba@oakland.edu [Department of Biological Sciences, Oakland University, Rochester, Michigan (United States)

    2013-12-01

    Purpose: To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model. Methods and Materials: Lewis lung carcinoma tumors were established in C57BL/6 mice and irradiated with 30 Gy given as 2 fractions over 2 days. Tumors were imaged with positron emission tomography/computed tomography (PET/CT) and measured daily with digital calipers. The HSPC and myelomonocytic cell content was assessed via immunofluorescent staining and flow cytometry. Functionality of tumor-associated HSPCs was verified in vitro using colony-forming cell assays and in vivo by rescuing lethally irradiated C57BL/6 recipients. Results: Irradiation significantly reduced tumor volumes and tumor regrowth rates compared with nonirradiated controls. The number of CD133{sup +} HSPCs present in irradiated tumors was higher than in nonirradiated tumors during all stages of regrowth. CD11b{sup +} counts were similar. PET/CT imaging and growth rate analysis based on standardized uptake value indicated that HSPC recruitment directly correlated to the extent of regrowth and intratumor cell activity after irradiation. The BM-derived tumor-associated HSPCs successfully formed hematopoietic colonies and engrafted irradiated mice. Finally, targeted treatment with a small animal radiation research platform demonstrated localized HSPC recruitment to defined tumor subsites exposed to radiation. Conclusions: Hypofractionated irradiation resulted in a pronounced and targeted recruitment of BM-derived HSPCs, possibly as a mechanism to promote tumor regrowth. These data indicate for the first time that radiation therapy regulates HSPC content within regrowing tumors.

  7. Central nervous system tumors

    International Nuclear Information System (INIS)

    Central nervous system (CNS) tumors are relatively common in veterinary medicine, with most diagnoses occurring in the canine and feline species. Numerous tumor types from various cells or origins have been identified with the most common tumors being meningiomas and glial cell tumors. Radiation therapy is often used as an aid to control the clinical signs associated with these neoplasms. In general, these tumors have a very low metastatic potential, such that local control offers substantial benefit. Experience in veterinary radiation oncology would indicate that many patients benefit from radiation treatment. Current practice indicates the need for computed tomography or magnetic resonance imaging studies. These highly beneficial studies are used for diagnosis, treatment planning, and to monitor treatment response. Improvements in treatment planning and radiation delivered to the tumor, while sparing the normal tissues, should improve local control and decrease potential radiation related problems to the CNS. When possible, multiple fractions of 3 Gy or less should be used. The tolerance dose to the normal tissue with this fractionation schedule is 50 to 55 Gy. The most common and serious complications of radiation for CNS tumors is delayed radiation myelopathy and necrosis. Medical management of the patient during radiation therapy requires careful attention to anesthetic protocols, and medications to reduce intracranial pressure that is often elevated in these patients. Canine brain tumors have served as an experimental model to test numerous new treatments. Increased availability of advanced imaging modalities has spawned increased detection of these neoplasms. Early detection of these tumors with appropriate aggressive therapy should prove beneficial to many patients

  8. Generation of axolotl hematopoietic chimeras

    Directory of Open Access Journals (Sweden)

    David Lopez

    2015-02-01

    Full Text Available Wound repair is an extremely complex process that requires precise coordination between various cell types including immune cells.  Unfortunately, in mammals this usually results in scar formation instead of restoration of the original fully functional tissue, otherwise known as regeneration.  Various animal models like frogs and salamanders are currently being studied to determine the intracellular and intercellular pathways, controlled by gene expression, that elicit cell proliferation, differentiation, and migration of cells during regenerative healing.  Now, the necessary genetic tools to map regenerative pathways are becoming available for the axolotl salamander, thus allowing comparative studies between scarring and regeneration.  Here, we describe in detail three methods to produce axolotl hematopoietic cell-tagged chimeras for the study of hematopoiesis and regeneration.

  9. Short Stat5-interacting peptide derived from phospholipase C-β3 inhibits hematopoietic cell proliferation and myeloid differentiation.

    Directory of Open Access Journals (Sweden)

    Hiroki Yasudo

    Full Text Available Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to various hematopoietic malignancies including myeloproliferative neoplasm (MPN. Our recent study found that phospholipase C (PLC-β3 is a novel tumor suppressor involved in MPN, lymphoma and other tumors. Stat5 activity is negatively regulated by the SH2 domain-containing protein phosphatase SHP-1 in a PLC-β3-dependent manner. PLC-β3 can form the multimolecular SPS complex together with SHP-1 and Stat5. The close physical proximity of SHP-1 and Stat5 brought about by interacting with the C-terminal segment of PLC-β3 (PLC-β3-CT accelerates SHP-1-mediated dephosphorylation of Stat5. Here we identify the minimal sequences within PLC-β3-CT required for its tumor suppressor function. Two of the three Stat5-binding noncontiguous regions, one of which also binds SHP-1, substantially inhibited in vitro proliferation of Ba/F3 cells. Surprisingly, an 11-residue Stat5-binding peptide (residues 988-998 suppressed Stat5 activity in Ba/F3 cells and in vivo proliferation and myeloid differentiation of hematopoietic stem/progenitor cells. Therefore, this study further defines PLC-β3-CT as the Stat5- and SHP-1-binding domain by identifying minimal functional sequences of PLC-β3 for its tumor suppressor function and implies their potential utility in the control of hematopoietic malignancies.

  10. SNP Array in Hematopoietic Neoplasms: A Review

    Science.gov (United States)

    Song, Jinming; Shao, Haipeng

    2015-01-01

    Cytogenetic analysis is essential for the diagnosis and prognosis of hematopoietic neoplasms in current clinical practice. Many hematopoietic malignancies are characterized by structural chromosomal abnormalities such as specific translocations, inversions, deletions and/or numerical abnormalities that can be identified by karyotype analysis or fluorescence in situ hybridization (FISH) studies. Single nucleotide polymorphism (SNP) arrays offer high-resolution identification of copy number variants (CNVs) and acquired copy-neutral loss of heterozygosity (LOH)/uniparental disomy (UPD) that are usually not identifiable by conventional cytogenetic analysis and FISH studies. As a result, SNP arrays have been increasingly applied to hematopoietic neoplasms to search for clinically-significant genetic abnormalities. A large numbers of CNVs and UPDs have been identified in a variety of hematopoietic neoplasms. CNVs detected by SNP array in some hematopoietic neoplasms are of prognostic significance. A few specific genes in the affected regions have been implicated in the pathogenesis and may be the targets for specific therapeutic agents in the future. In this review, we summarize the current findings of application of SNP arrays in a variety of hematopoietic malignancies with an emphasis on the clinically significant genetic variants.

  11. The point of WHO classification of tumors of hematopoietic and lymphold tissues(2008)%2008年版"世界卫生组织造血及淋巴组织肿瘤分类"指要

    Institute of Scientific and Technical Information of China (English)

    曹履先

    2009-01-01

    In introduced the 4th edition(2008)of WHO classification of tumors of haematopoietic and lymphoid tissues.They are divided into 12 columns,which includes myeloproliferative neoplasms;myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDDFRA,PDDFRB or FGFR1;myelodysplastic/myeloproliferative neoplasms;myelodysplastic syndromes;acute myeloid leukemia(AML)and related precursor neoplasms;acute leukemia of ambiguous lineage;precursor lymphoid neoplasms;mature Bcell neoplasms;mature T-cell and NK-cell neoplasms;Hodgkin lymphoma;histocytic and dendritic cell neoplasms;post-transplant lymphoproliferative disorders(PTLD).Accroding to the progression of the molecular biology,the new classifications combines a lot of the new knowledge with gene, chromosome,immunophenotypes,morphology,histocytology et al.The chronic myeloproliferative disorders changes into myeloproliferative neoplasms(MPN),mastocytosis included in this column of MPN.There are three subdivisions in the column of myeloid and lymphoid neoplasms with eosinophilia and abnormalities of genes.Refractory anemia with ring sideroblasts associated with marked thrombocytosis(RARS-T)in the column of MDS/MPN.In the column of MDS,MDS in children is added.Myeloid sarcoma,Down syndrome with myeloid proliferation and blastic plasmacytoid dendritic cell neoplasm were added in the column of AML and related precursor neoplasms.Acute leukemia of ambiguous lineage includes 6 kinds neoplasms.Precursor lymphoid neoplasms (B & T cells)includes leukemias and lymphomas,the bone marrow lymphoblasts>25% is defined as leukemia(no lower limit 20% as AML).Mature B-cell(39 neoplasms),T/NK cell neoplasms(22 neoplasms),Hodgkin lymphoma (6 neoplasms),histocytic and dendritic cell neoplasms (7 neoplasms).Post transplant lymphoproliferative disorders(PTLD)forms a new colunlns(5 neoplasms).%2008年第4版"世界卫生组织造血及淋巴组织肿瘤分类"把该类肿瘤分列为12个项目,对分子生物学进展结合较

  12. Natural killer cells in non-hematopoietic malignancies.

    Science.gov (United States)

    Desbois, Mélanie; Rusakiewicz, Sylvie; Locher, Clara; Zitvogel, Laurence; Chaput, Nathalie

    2012-01-01

    Natural killer (NK) cells belong to the innate immune system and were initially described functionallywise by their spontaneous cytotoxic potential against transformed or virus-infected cells. A delicate balance between activating and inhibiting receptors regulates NK cell tolerance. A better understanding of tissue resident NK cells, of NK cell maturation stages and migration patterns has evolved allowing a thoughtful evaluation of their modus operandi. While evidence has been brought up for their relevance as gate keepers in some hematopoietic malignancies, the role of NK cells against progression and dissemination of solid tumors remains questionable. Hence, many studies pointed out the functional defects of the rare NK cell infiltrates found in tumor beds and the lack of efficacy of adoptively transferred NK cells in patients. However, several preclinical evidences suggest their anti-metastatic role in a variety of mouse tumor models. In the present review, we discuss NK cell functions according to their maturation stage and environmental milieu, the receptor/ligand interactions dictating tumor cell recognition and recapitulate translational studies aimed at deciphering their prognostic or predictive role against human solid malignancies. PMID:23269924

  13. BNCT of canine osteosarcoma

    International Nuclear Information System (INIS)

    A dog was diagnosed with osteosarcoma (8x6x5cm) in the right wing of ilium by radiography, radionuclide scintigraphy and histological study of biopsy material. The treatment plan was as follows: γ-therapy in combination with chemotherapy; prevention of hematogenous pulmonary metastases by the transfusion of 130 ml of allogenic marrow from a healthy donor; administration of 11.4g 10B-boronphenylalanine into the right iliac artery; resection of the right iliac wing with the osteosarcoma lesion; neutron irradiation (MEPhI Reactor) of the bone fragment (dose on healthy osteocytes - 15±4 Gy (W), on tumor - 50±9 Gy (W); reimplantation and fixation of the fragment; three courses of adjuvant chemotherapy. The doses were determined in full-scale calculations of the reactor radiation fields with a model of the bone under the code RADUGA. The 10B concentration (μg/g) in the bone was: normal tissue - 9±3, tumor - 28±5. In 24 hours post operation the dog was able to walk using the treated limb, and 6 months later it moved freely. The patient has been under observation for 30 months. The results of the research demonstrate complete cure. The use of similar treatment plans improves the therapeutic efficiency of BNCT. (author)

  14. BAF180 regulates cellular senescence and hematopoietic stem cell homeostasis through p21.

    Science.gov (United States)

    Lee, Hyemin; Dai, Fangyan; Zhuang, Li; Xiao, Zhen-Dong; Kim, Jongchan; Zhang, Yilei; Ma, Li; You, M James; Wang, Zhong; Gan, Boyi

    2016-04-12

    BAF180 (also called PBRM1), a subunit of the SWI/SNF complex, plays critical roles in the regulation of chromatin remodeling and gene transcription, and is frequently mutated in several human cancers. However, the role of mammalian BAF180 in tumor suppression and tissue maintenance in vivo remains largely unknown. Here, using a conditional somatic knockout approach, we explored the cellular and organismal functions of BAF180 in mouse. BAF180 deletion in primary mouse embryonic fibroblasts (MEFs) triggers profound cell cycle arrest, premature cellular senescence, without affecting DNA damage response or chromosomal integrity. While somatic deletion of BAF180 in adult mice does not provoke tumor development, BAF180 deficient mice exhibit defects in hematopoietic system characterized by progressive reduction of hematopoietic stem cells (HSCs), defective long-term repopulating potential, and hematopoietic lineage developmental aberrations. BAF180 deletion results in elevated p21 expression in both MEFs and HSCs. Mechanistically, we showed that BAF180 binds to p21 promoter, and BAF180 deletion enhances the binding of modified histones associated with transcriptional activation on p21 promoter. Deletion of p21 rescues cell cycle arrest and premature senescence in BAF180 deficient MEFs, and partially rescues hematopoietic defects in BAF180 deficient mice. Together, our study identifies BAF180 as a critical regulator of cellular senescence and HSC homeostasis, which is at least partially regulated through BAF180-mediated suppression of p21 expression. Our results also suggest that senescence triggered by BAF180 inactivation may serve as a failsafe mechanism to restrain BAF180 deficiency-associated tumor development, providing a conceptual framework to further understand BAF180 function in tumor biology.

  15. Comparative Aspects of Molecular Mechanisms of Drug Resistance through ABC Transporters and Other Related Molecules in Canine Lymphoma

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    Hirotaka Tomiyasu

    2015-08-01

    Full Text Available The most important causes of treatment failure in canine lymphoma include intrinsic or acquired drug resistance. Thus, elucidation of molecular mechanisms of drug resistance is essential for the establishment of better treatment alternatives for lymphoma patients. The overexpression of drug transporters is one of the most intensively studied mechanisms of drug resistance in many tumors. In canine lymphoma, it has also been shown that the overexpression of drug efflux pumps such as P-glycoprotein is associated with drug-resistant phenotypes. Canine lymphoma has many pathological similarities to human non-Hodgkin’s lymphoma, and they also share similar molecular mechanisms of drug resistance. We have previously demonstrated the association of the overexpression of drug transporters with drug resistance and indicated some molecular mechanisms of the regulation of these transporters’ expressions in canine and human lymphoid tumor cells. However, it has also been indicated that other known or novel drug resistance factors should be explored to overcome drug resistance in lymphoma. In this review, we summarize the recent findings on the molecular mechanisms of drug resistance and possible strategies to develop better treatment modalities for canine lymphoma from the comparative aspects with human lymphoid tumors.

  16. Surgical innovations in canine gonadectomy

    OpenAIRE

    Van Goethem, Bart

    2016-01-01

    In this thesis some recent technological developments in human surgery are evaluated for their potential use in veterinary medicine by introducing them as surgical innovations for canine gonadectomy. Barbed sutures achieve wound apposition without surgical knot tying and thus avoid knot-associated negative consequences (lengthy placement, impaired wound healing around bulky knots, and the effect of unsightly knots on cosmetics). A study in 9 dogs found that celiotomy closure was easily achiev...

  17. Genome Sequence of Canine Herpesvirus.

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    Konstantinos V Papageorgiou

    Full Text Available Canine herpesvirus is a widespread alphaherpesvirus that causes a fatal haemorrhagic disease of neonatal puppies. We have used high-throughput methods to determine the genome sequences of three viral strains (0194, V777 and V1154 isolated in the United Kingdom between 1985 and 2000. The sequences are very closely related to each other. The canine herpesvirus genome is estimated to be 125 kbp in size and consists of a unique long sequence (97.5 kbp and a unique short sequence (7.7 kbp that are each flanked by terminal and internal inverted repeats (38 bp and 10.0 kbp, respectively. The overall nucleotide composition is 31.6% G+C, which is the lowest among the completely sequenced alphaherpesviruses. The genome contains 76 open reading frames predicted to encode functional proteins, all of which have counterparts in other alphaherpesviruses. The availability of the sequences will facilitate future research on the diagnosis and treatment of canine herpesvirus-associated disease.

  18. Alkylation and Carbamylation Effects of Lomustine and Its Major Metabolites and MGMT Expression in Canine Cells

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    Thushara Chakkath

    2015-04-01

    Full Text Available DNA Alkylation is thought to be the reason for the efficacy of lomustine while carbamylation has been implicated as the cause for the side effects seen with lomustine treatment such as hepatotoxicity. In the alkylation study we show that lomustine and its metabolites form similar levels of the DNA adducts N7 hydroxyethylguanine and O6 hydroxyethyldeoxyguanosine. In terms of carbamylation, lomustine showed greater extent of carbamylation in the canine hepatocytes and lymphoma cell lines. The DNA repair enzyme O6 methylguanine DNA methyltransferase (MGMT causes resistance of tumor cells to bifunctional nitrosourea, like lomustine. There is no data available regarding MGMT expression/activity in canine cells or tissues. Our study shows that there is low MGMT activity in the canine lymphoid cell line 17–71 while the GL-1 cells did not show any detectable enzyme activity or mRNA expression. The MGMT enzyme activity measured in canine hepatocytes is about 250–350 fmol/mg protein as compared to about 90 fmol/mg protein in 17–71 cells. We also show that MGMT mRNA expression in 17–71 cells and canine hepatocytes positively correlates with its enzyme activity in these cells.

  19. Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

    International Nuclear Information System (INIS)

    Human hemangiosarcoma (HSA) tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes. Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF)-A, basic fibroblast growth factors (bFGF), flt-1 and flk-1 (receptors of VEGF-A), FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR), using canine-specific primer sets. Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF) was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the other tumors. We established 6 xenograft canine HSA

  20. Bullous pemphigoid after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kato, Keisuke; Koike, Kazutoshi; Kobayashi, Chie; Iijima, Shigeruko; Hashimoto, Takashi; Tsuchida, Masahiro

    2015-06-01

    Bullous pemphigoid (BP) is an autoimmune skin disorder characterized by subepidermal blisters due to deposit of autoantibody against dermal basement membrane protein. It has been reported that BP can occur after allogeneic hematopoietic stem cell transplantation (HSCT). We describe a patient with BP having autoantibody against BP180 after unrelated-donor HSCT against T lymphoblastic leukemia. The patient was treated with steroid leading to complete resolution of BP, but T lymphoblastic leukemia progressed rapidly after steroid hormone treatment. Given that immunosuppressant may reduce graft-versus-tumor effect, immunomodulatory agents such as nicotinamide and tetracycline, erythromycin, and immunoglobulin may be appropriate as soon as typical blister lesions are seen after HSCT. PMID:26113316

  1. Immunological Basis of Bone Marrow Failure after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Masouridi-Levrat, Stavroula; Simonetta, Federico; Chalandon, Yves

    2016-01-01

    Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells. We next summarize the current knowledge about the contribution of inflammatory mediators to the development of PGF. In situations of chronic inflammation complicating allo-HSCT, such as graft-versus-host disease or infections, PGF seems to be essentially the result of a sustained impairment of hematopoietic stem cells (HSC) self-renewal and proliferation caused by inflammatory mediators, such as interferon-γ (IFN-γ) and tumor necrosis factor-α, and of induction of apoptosis through the Fas/Fas ligand pathway. Interestingly, the production of inflammatory molecules leads to a non-MHC restricted, bystander inhibition of hematopoiesis, therefore, representing a promising target for immunological interventions. Finally, we discuss immune-mediated impairment of bone marrow microenvironment as a potential mechanism hampering hematopoietic recovery. Better understanding of immunological mechanisms responsible for BMF syndromes after allo-HSCT may lead to the development of more efficient immunotherapeutic interventions. PMID:27695456

  2. Control of AC133/CD133 and impact on human hematopoietic progenitor cells through nucleolin.

    Science.gov (United States)

    Bhatia, S; Reister, S; Mahotka, C; Meisel, R; Borkhardt, A; Grinstein, E

    2015-11-01

    AC133 is a prominent surface marker of CD34+ and CD34- hematopoietic stem/progenitor cell (HSPC) subsets. AC133+ HSPCs contain high progenitor cell activity and are capable of hematopoietic reconstitution. Furthermore, AC133 is used for prospective isolation of tumor-initiating cells in several hematological malignancies. Nucleolin is a multifunctional factor of growing and cancer cells, which is aberrantly active in certain hematological neoplasms, and serves as a candidate molecular target for cancer therapy. Nucleolin is involved in gene transcription and RNA metabolism and is prevalently expressed in HSPCs, as opposed to differentiated hematopoietic tissue. The present study dissects nucleolin-mediated activation of surface AC133 and its cognate gene CD133, via specific interaction of nucleolin with the tissue-dependent CD133 promoter P1, as a mechanism that crucially contributes to AC133 expression in CD34+ HSPCs. In mobilized peripheral blood (MPB)-derived HSPCs, nucleolin elevates colony-forming unit (CFU) frequencies and enriches granulocyte-macrophage CFUs. Furthermore, nucleolin amplifies long-term culture-initiating cells and also promotes long-term, cytokine-dependent maintenance of hematopoietic progenitor cells. Active β-catenin, active Akt and Bcl-2 levels in MPB-derived HSPCs are nucleolin-dependent, and effects of nucleolin on these cells partially rely on β-catenin activity. The study provides new insights into molecular network relevant to stem/progenitor cells in normal and malignant hematopoiesis. PMID:26183533

  3. Effects of carnosine on cyclophosphamide-induced hematopoietic suppression in mice.

    Science.gov (United States)

    Xu, Meng; He, Rong-Rong; Zhai, Yu-Jia; Abe, Keiichi; Kurihara, Hiroshi

    2014-01-01

    Cyclophosphamide is one of the most widely used chemotherapeutic agents in treating cancers. Chemotherapy drug-induced oxidative stress produces side effects. The severity of myelosuppression increases with a high dose of cyclophosphamide. Chicken soup or chicken essence, a traditional Chinese aliment, is a popular health supplement for patients with cancers or other diseases in Asia. As a major functional component of chicken meat extract, carnosine (beta-alanyl-L-histidine), a dipeptide of the amino acids beta-alanine and histidine, has been shown to have strong antioxidant activities. In the present study, we investigated the effects of carnosine on hematopoietic suppression in mice treated with cyclophosphamide. As expected, we found that cyclophosphamide administration (with a single dose of 150 mg/kg) induced a rapid (within 24 hours) and severe hematopoietic suppression in mice. We further showed that carnosine administration (100 mg/kg/day or 200 mg/kg/day for continuous seven days) could substantially improve suppressed hematopoietic functions and accelerate the recovery of leukocyte counts, bone marrow spontaneous proliferation, colony stimulating activity (CSA) in serum, and production of endogenous cytokines such as interleukin-3 (IL-3) and stem cell factor (SCF). These results indicate that carnosine has the potential to promote the recovery from hematopoietic suppression induced by cyclophosphamide. Our data suggest that carnosine holds a potential in clinical application to minimize the side effects induced by chemotherapeutic agents such as cyclophosphamide and thus will substantially improve the overall anti-tumor effects of the standard chemotherapies. PMID:24467540

  4. Nodular Epiescleritis Granulomatous Canine. Case Report

    Directory of Open Access Journals (Sweden)

    Camilo Guarín Patarroyo

    2011-12-01

    Full Text Available Granulomatous epiescleritis nodular disease in canines is a very unusual presentation that affects or external fibrous tunic of the eyeball and conjunctiva, which was an increase similar to a unilateral or bilateral tumor. Suspected immune-mediated disease due to lack of identification of an etiologic agent and the response to treatment with immunosuppressive drugs (Couto, 1992. The ideal therapy is the application of steroids via intralesional, topical or systemic, or other immunosuppressants such as cyclosporine and azathioprine; it is still advisable to apply antibiotic is the ideal combination of tetracycline and neomycin (Gilger & Whitley, 1999. The diagnostic method of episcleritis is made by histopathology, which is evident in changes similar to chronic granulomatous inflammation. Are claiming a racial bias in Alsatian, Shepherd Collie Shetland Shepherd, Coker Spaniel, Rottweiler and Labrador Retriever (Gough & Thomas, 2004. The following case is a report of a nodular epiescleritis affecting the cornea, sclera, and the corneoscleral limbus, which describes the diagnosis, signology and treatment.

  5. Advance in hematopoietic stem cells transplantation for leukemia

    Institute of Scientific and Technical Information of China (English)

    HUANG Xiao-jun

    2008-01-01

    @@ During the past 50 years, intensive studies into the characteristics of hematopoietic stem cell transplantation immunology and the emergence of new immunosuppressant and anti-infective drugs have significantly improved the clinical result of hematopoietic stem cell transplantation (HSCT).

  6. uPAR EXPRESSION IN CANINE NORMAL PROSTATE AND WITH PROLIFERATIVE DISORDERS

    Directory of Open Access Journals (Sweden)

    Mariana Rodrigues Faleiro

    2013-06-01

    Full Text Available Prostatic lesions such as prostatic intraepithelial neoplasia (PIN and proliferative inflammatory atrophy (PIA are studied in human and canine species due to their malignance potential. The plasminogen activator (PA system has been suggested to play a central role in cell adhesion, angiogenesis, inflammation, and tumor invasion. The urokinase-type plasminogen activator receptor (uPAR is a component of the PA, with a range of expression in tumor and stromal cells. In this study, uPAR expression in both canine normal prostates and with proliferative disorders (benign prostatic hyperplasia-BPH, proliferative inflammatory atrophy-PIA, prostatic intraepithelial neoplasia-PIN, and carcinoma-PC was evaluated by immunohistochemistry in a tissue microarray (TMA slide to establish the role of this enzyme in extracellular matrix (ECM remodeling and in the processes of tissue invasion. A total of 298 cores and 355 diagnoses were obtained, with 36 (10.1% normal prostates, 46 (13.0% with BPH, 128 (36.1% with PIA, 74 (20.8% with PIN and 71 (20.0% with PC. There is variation in the expression of uPAR in canine prostate according to the lesion, with lower expression in normal tissue and with BPH, and higher expression in tissue with PIA, PIN and PC. The high expression of uPAR in inflammatory and neoplastic microenvironment indicates increased proteolytic activity in canine prostates with PIA, PIN, and PC.

  7. Intrinsic Radiosensitivity and Cellular Characterization of 27 Canine Cancer Cell Lines.

    Science.gov (United States)

    Maeda, Junko; Froning, Coral E; Brents, Colleen A; Rose, Barbara J; Thamm, Douglas H; Kato, Takamitsu A

    2016-01-01

    Canine cancer cell lines have progressively been developed, but are still underused resources for radiation biology research. Measurement of the cellular intrinsic radiosensitivity is important because understanding the difference may provide a framework for further elucidating profiles for prediction of radiation therapy response. Our studies have focused on characterizing diverse canine cancer cell lines in vitro and understanding parameters that might contribute to intrinsic radiosensitivity. First, intrinsic radiosensitivity of 27 canine cancer cell lines derived from ten tumor types was determined using a clonogenic assay. The 27 cell lines had varying radiosensitivities regardless tumor type (survival fraction at 2 Gy, SF2 = 0.19-0.93). In order to understand parameters that might contribute to intrinsic radiosensitivity, we evaluated the relationships of cellular radiosensitivity with basic cellular characteristics of the cell lines. There was no significant correlation of SF2 with S-phase fraction, doubling time, chromosome number, ploidy, or number of metacentric chromosomes, while there was a statistically significant correlation between SF2 and plating efficiency. Next, we selected the five most radiosensitive cell lines as the radiosensitive group and the five most radioresistant cell lines as the radioresistant group. Then, we evaluated known parameters for cell killing by ionizing radiation, including radiation-induced DNA double strand break (DSB) repair and apoptosis, in the radiosensitive group as compared to the radioresistant group. High levels of residual γ-H2AX foci at the sites of DSBs were present in the four out of the five radiosensitive canine cancer cell lines. Our studies suggested that substantial differences in intrinsic radiosensitivity exist in canine cancer cell lines, and radiation-induced DSB repair was related to radiosensitivity, which is consistent with previous human studies. These data may assist further investigations

  8. 9 CFR 113.306 - Canine Distemper Vaccine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... distemper virus, each of five canine distemper susceptible ferrets shall be injected with a sample of...

  9. Canine and feline parasitic zoonoses in China

    Directory of Open Access Journals (Sweden)

    Chen Jia

    2012-07-01

    Full Text Available Abstract Canine and feline parasitic zoonoses have not been given high priority in China, although the role of companion animals as reservoirs for zoonotic parasitic diseases has been recognized worldwide. With an increasing number of dogs and cats under unregulated conditions in China, the canine and feline parasitic zoonoses are showing a trend towards being gradually uncontrolled. Currently, canine and feline parasitic zoonoses threaten human health, and cause death and serious diseases in China. This article comprehensively reviews the current status of major canine and feline parasitic zoonoses in mainland China, discusses the risks dogs and cats pose with regard to zoonotic transmission of canine and feline parasites, and proposes control strategies and measures.

  10. Prevalência das dermatopatias não-tumorais em cães do município de Santa Maria, Rio Grande do Sul (2005-2008 Prevalence of non-tumorous canine dermatopathies in dogs from the municipality of Santa Maria, Rio Grande do Sul, Brazil (2005-2008

    Directory of Open Access Journals (Sweden)

    Tatiana M. Souza

    2009-02-01

    prevalence of non-tumorous canine dermatopathies affecting dogs from the municipality of Santa Maria, Rio Grande do Sul, Brazil. From March 2005 to June de 2008, the authors followed-up canine dermatological cases from two sources: those referred to the Dermatology Sector of the Veterinary Teaching Hospital at the Universidade Federal de Santa Maria and those from a private practice. During this period 480 dogs with dermatological problems were examined; in 393 (81.9% it was possible to establish a definitive diagnosis and in 87 (18.1% the diagnosis was inconclusive. Four hundred and twenty four primary diagnosis and 78 secondary diagnosis were performed in the 393 dogs with conclusive diagnosis, totaling 502 diagnosis. The distribution of the diagnosis according to the categories of diagnosed dermatopathies was as follows: Allergic (190/502 [37.8%], bacterial (103/502 [20.5%], parasitic (97/502 [19.3%], environmental (28/502 [5,6%], mycotic (20/502 [4.0%], endocrine (13/502 [2.6%], keratinization disturbances (11/502 [2.2%], psychogenic (9/502 [1.8%], acquired alopecias (6/502 [1.2%], autoimmune (6/502 [1.2%], inherited (6/502 [1.2%], pigmentary disturbances (1/502 [0.2%], nutritional (1/502 [0.2%], and sundry conditions (11/502 [2.2%]. In general, the ten most frequently diagnosed non-tumorous dermatopathies in decreasing order of frequency were: Atopy, flea bite allergic dermatitis, bacterial folliculitis, demodectic mange, deep bacterial folliculitis/furunculosis, sarcoptic mange, myiasis, food allergy, traumatic pyoderma, and Malassezia dermatitis. These 10 conditions together made up approximately for three quarters of all canine skin diseases diagnosed in the current study.

  11. Long-term in vivo provision of antigen-specific T cell immunity by programming hematopoietic stem cells

    Science.gov (United States)

    Yang, Lili; Baltimore, David

    2005-03-01

    A method to genetically program mouse hematopoietic stem cells to develop into functional CD8 or CD4 T cells of defined specificity in vivo is described. For this purpose, a bicistronic retroviral vector was engineered that efficiently delivers genes for both and chains of T cell receptor (TCR) to hematopoietic stem cells. When modified cell populations were used to reconstruct the hematopoietic lineages of recipient mice, significant percentages of antigen-specific CD8 or CD4 T cells were observed. These cells expressed normal surface markers and responded to peptide antigen stimulation by proliferation and cytokine production. Moreover, they could mature into memory cells after peptide stimulation. Using TCRs specific for a model tumor antigen, we found that the recipient mice were able to partially resist a challenge with tumor cells carrying the antigen. By combining cells modified with CD8- and CD4-specific TCRs, and boosting with dendritic cells pulsed with cognate peptides, complete suppression of tumor could be achieved and even tumors that had become established would regress and be eliminated after dendritic cell/peptide immunization. This methodology of "instructive immunotherapy" could be developed for controlling the growth of human tumors and attacking established pathogens.

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

    Science.gov (United States)

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

    2013-04-15

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

  13. Three-dimensional magnetic resonance reconstruction images before and after surgical therapy of spontaneous canine brain tumors Imagens de reconstrução tri-dimensional por ressonância magnética antes e depois de tratamento cirúrgico de tumores cerebrais espontâneos caninos

    Directory of Open Access Journals (Sweden)

    Julio Carlos Canola

    2007-08-01

    Full Text Available Specific software was used for reconstruction of spontaneous intracranial tumor volume from magnetic resonance images (MRI in three dogs. Histopathologically confirmed meningioma, cystic meningioma, and choroid plexus tumors were evaluated before and after surgery. The software allowed the whole-volume segmentation of the skin, brain, tumor, edema, and cyst. Manipulation of the three-dimensional images (3D allowed visualization of all anatomical structures, aided clinical understanding, surgical planning, and treatment monitoring.Um programa de computador específico foi utilizado para reconstrução do volume tumoral intracraniano espontâneo por imagens de ressonância magnética (IRM em três cães. Tumores histopatologicamente confirmados como meningioma, meningioma cístico e tumor do plexo coróide foram avaliados antes e após cirurgia. O programa de computador permitiu a segmentação por completo da pele, do cérebro, do tumor, do edema e do cisto. A manipulação das imagens tridimensionais permitiu a visibilização de todas as estruturas anatômicas, além da compreensão clínica, do planejamento cirúrgico e da monitorização do tratamento.

  14. Human hematopoietic cell culture, transduction, and analyses

    DEFF Research Database (Denmark)

    Bonde, Jesper; Wirthlin, Louisa; Kohn, Donald B;

    2008-01-01

    This unit provides methods for introducing genes into human hematopoietic progenitor cells. The Basic Protocol describes isolation of CD34(+) cells, transduction of these cells with a retroviral vector on fibronectin-coated plates, assaying the efficiency of transduction, and establishing long......-term cultures. Support protocols describe methods for maintenance of vector-producing fibroblasts (VPF) and supernatant collection from these cells, screening medium components for the ability to support hematopoietic cell growth, and establishing colonies from long-term cultures. Other protocols provide PCR...

  15. Alpha-1-antitrypsin studies: canine serum and canine surfactant protein

    International Nuclear Information System (INIS)

    Canine serum alpha-1-antitrypsin was isolated by gel filtration and affinity chromatography and characterized by polyacrylamide gel electrophoresis and immunoelectrophoresis. Measurement of the trypsin inhibitory capacity of the separated protein indicated a ninefold concentration of functional trypsin inhibitor during the isolation procedure. Electrophoresis demonstrated the presence of a single protein with alpha-globulin mobility and a molecular weight near that of human alpha-1-antitrypsin. The trypsin inhibitory capacity of pulmonary surfactant protein from five Beagle dogs was measured, related to total surfactant protein concentration, and compared with similar measurements on whole serum from the same animals. Results indicated a variable concentration of trypsin inhibitor in the canine pulmonary surfactant protein. However, the concentration in the surfactant protein was always significantly higher than that in the corresponding serum sample. Preliminary experiments designed to separate the trypsin inhibitory fraction(s) from the other surfactant proteins by gel filtration chromatography indicated that the trypsin inhibitor was probably a single protein with a molecular weight near that of alpha-1-antitrypsin. (U.S.)

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

    Directory of Open Access Journals (Sweden)

    Julia Beck

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

  17. Clinical and serological response of wild dogs (Lycaon pictus) to vaccination against canine distemper, canine parvovirus infection and rabies

    OpenAIRE

    J. Van Heerden; J. Bingham; M. Van Vuuren; R.E.J. Burroughs; E. Stylianides

    2002-01-01

    Wild dogs Lycaon pictus (n = 8) were vaccinated 4 times against canine distemper (n = 8) (initially with inactivated and subsequently with live attenuated strains of canine distemper) and canine parvovirus infection (n = 8) over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use ...

  18. Cardiac Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J.; Llanos-Gómez, Juan M.; Cabello-Rodríguez, Ana I.; Ramos-López, María

    2016-01-01

    Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called “sanctuaries,” are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass. PMID:27642531

  19. Unrelated hematopoietic stem cell registry and the role of the Hematopoietic Stem Cell Bank

    OpenAIRE

    Beom, Su-Hee; Kim, Eung Jo; Kim, Miok; Kim, Tai-Gyu

    2016-01-01

    Background The hematopoietic stem cell bank has been actively recruiting registrants since 1994. This study systematically reviews its operations and outcomes over the last 20 years. Methods Retrospective data on a total of 47,711 registrants were reviewed. Relevant data were processed using PASW Statistics for Windows, version 18.0. Results As of 2013, the Korean Network for Organ Sharing database contained 265,307 registrants. Of these, 49,037 (18%) registrants committed to hematopoietic ce...

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

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    Farruk M. Lutful Kabir

    2015-12-01

    Full Text Available Breast cancer represents the second most frequent neoplasm in humans and sexually intact female dogs after lung and skin cancers, respectively. Many similar features in human and dog cancers including, spontaneous development, clinical presentation, tumor heterogeneity, disease progression and response to conventional therapies have supported development of this comparative model as an alternative to mice. The highly conserved similarities between canine and human genomes are also key to this comparative analysis, especially when compared to the murine genome. Studies with canine mammary tumor (CMT models have shown a strong genetic correlation with their human counterparts, particularly in terms of altered expression profiles of cell cycle regulatory genes, tumor suppressor and oncogenes and also a large group of non-coding RNAs or microRNAs (miRNAs. Because CMTs are considered predictive intermediate models for human breast cancer, similarities in genetic alterations and cancer predisposition between humans and dogs have raised further interest. Many cancer-associated genetic defects critical to mammary tumor development and oncogenic determinants of metastasis have been reported and appear to be similar in both species. Comparative analysis of deregulated gene sets or cancer signaling pathways has shown that a significant proportion of orthologous genes are comparably up- or down-regulated in both human and dog breast tumors. Particularly, a group of cell cycle regulators called cyclin-dependent kinase inhibitors (CKIs acting as potent tumor suppressors are frequently defective in CMTs. Interestingly, comparative analysis of coding sequences has also shown that these genes are highly conserved in mammals in terms of their evolutionary divergence from a common ancestor. Moreover, co-deletion and/or homozygous loss of the INK4A/ARF/INK4B (CDKN2A/B locus, encoding three members of the CKI tumor suppressor gene families (p16/INK4A, p14ARF and p15

  1. Prognostic markers of canine pyometra

    Directory of Open Access Journals (Sweden)

    M.C. Sant'Anna

    2014-12-01

    Full Text Available The pyometra is a disease that affects middle age and elderly female dogs during diestrus. Hormonal, microbiological, biochemical and hematological aspects are well described. However, few studies have evaluated the role of each in the prognosis of canine pyometra. The aim of this study was to identify markers associated with clinical worsening of dogs with pyometra. We prospectively evaluated 80 dogs with pyometra treated surgically. Group 1 consisted of dogs that were discharged within 48 hours after surgery and Group 2 consisted of those who required prolonged hospitalization or died. The findings of hematological, biochemical and blood lactate levels were compared between groups and variables such as bacterial multidrug resistance, systemic inflammatory response syndrome (SIRS, hyperlactatemia and increased creatinine were analyzed through the dispersion of frequencies between groups. Among the variables studied, the presence of SIRS and elevated serum creatinine >2.5mg/mL were effective in predicting the worsening of the disease and can be used as prognostic markers of canine pyometra.

  2. Hematopoiesis and hematopoietic organs in arthropods.

    Science.gov (United States)

    Grigorian, Melina; Hartenstein, Volker

    2013-03-01

    Hemocytes (blood cells) are motile cells that move throughout the extracellular space and that exist in all clades of the animal kingdom. Hemocytes play an important role in shaping the extracellular environment and in the immune response. Developmentally, hemocytes are closely related to the epithelial cells lining the vascular system (endothelia) and the body cavity (mesothelia). In vertebrates and insects, common progenitors, called hemangioblasts, give rise to the endothelia and blood cells. In the adult animal, many differentiated hemocytes seem to retain the ability to proliferate; however, in most cases investigated closely, the bulk of hemocyte proliferation takes place in specialized hematopoietic organs. Hematopoietic organs provide an environment where undifferentiated blood stem cells are able to self-renew, and at the same time generate offspring that differentiate into different blood cell types. Hematopoiesis in vertebrates, taking place in the bone marrow, has been subject to intensive research by immunologists and stem cell biologists. Much less is known about blood cell formation in invertebrate animals. In this review, we will survey structural and functional properties of invertebrate hematopoietic organs, with a main focus on insects and other arthropod taxa. We will then discuss similarities, at the molecular and structural level, that are apparent when comparing the development of blood cells in hematopoietic organs of vertebrates and arthropods. Our comparative review is intended to elucidate aspects of the biology of blood stem cells that are more easily missed when focusing on one or a few model species. PMID:23319182

  3. Autonomous behavior of hematopoietic stem cells

    NARCIS (Netherlands)

    Kamminga, LM; Akkerman, [No Value; Weersing, E; Ausema, A; Dontje, B; Van Zant, G; de Haan, G

    2000-01-01

    Objective. Mechanisms that affect the function of primitive hematopoietic stem cells with long-term proliferative potential remain largely unknown. Here we assessed whether properties of stem cells are cell-extrinsically or cell-autonomously regulated. Materials and Methods. We developed a model in

  4. Hematopoietic stem cell transplantation in multiple sclerosis

    DEFF Research Database (Denmark)

    Rogojan, C; Frederiksen, J L

    2009-01-01

    Intensive immunosuppresion followed by hematopoietic stem cell transplantation (HSCT) has been suggested as potential treatment in severe forms of multiple sclerosis (MS). Since 1995 ca. 400 patients have been treated with HSCT. Stabilization or improvement occurred in almost 70% of cases at least...

  5. Hematopoietic stem cell transplantation for infantile osteopetrosis

    NARCIS (Netherlands)

    Orchard, Paul J.; Fasth, Anders L.; Le Rademacher, Jennifer L.; He, Wensheng; Boelens, Jaap Jan; Horwitz, Edwin M.; Al-Seraihy, Amal; Ayas, Mouhab; Bonfim, Carmem M.; Boulad, Farid; Lund, Troy; Buchbinder, David K.; Kapoor, Neena; OBrien, Tracey A.; Perez, Miguel A Diaz; Veys, Paul A.; Eapen, Mary

    2015-01-01

    We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HL

  6. Cellular memory and, hematopoietic stem cell aging

    NARCIS (Netherlands)

    Kamminga, Leonie M.; de Haan, Gerald

    2006-01-01

    Hematopoietic stem cells (HSCs) balance self-renewal and differentiation in order to sustain lifelong blood production and simultaneously maintain the HSC pool. However, there is clear evidence that HSCs are subject to quantitative and qualitative exhaustion. In this review, we briefly discuss sever

  7. In Vitro Action of Flavonoids in the Canine Malignant Histiocytic Cell Line DH82

    OpenAIRE

    Gabriel Silva; Ana Lúcia Fachin; Beleboni, Renê de O; Suzelei C. França; Mozart Marins

    2013-01-01

    Cancer is commonly diagnosed in dogs over the age of 10 and is a leading cause of death due to the lack of effective drugs. Flavonoids possess antioxidant, anti-inflammatory and anticarcinogenic properties and have been studied as chemopreventive agents in human cancer therapy. However, the literature on dogs is sparse. In this study, we analyzed the effect of nine flavonoids on cell viability, DNA damage and topoisomerase IIa/IIb gene expression in a canine tumor cell line (DH82). Apigenin, ...

  8. Modulation of carbohydrate residues in regenerative nodules and neoplasms of canine and feline pancreas.

    OpenAIRE

    Skutelsky, E.; Alroy, J.; Ucci, A. A.; Carpenter, J.L.; Moore, F. M.

    1987-01-01

    The glycoconjugates of regenerative acinar cells, acinic cell carcinomas, islet cell tumors, and normal canine and feline pancreas were studied. The authors used biotinylated lectins as probes and avidin-biotin-peroxidase complex as visualant to identify and to compare the distribution of carbohydrate residues on paraffin sections from 74 cases. The findings demonstrate a difference in the staining pattern between normal acinar, islet, and ductal cells in each species and small differences in...

  9. Anti-Influenza Neuraminidase Inhibitor Oseltamivir Phosphate Induces Canine Mammary Cancer Cell Aggressiveness

    OpenAIRE

    Joana T de Oliveira; Santos, Ana L.; Catarina Gomes; Rita Barros; Cláudia Ribeiro; Nuno Mendes; de Matos, Augusto J.; M. Helena Vasconcelos; Maria José Oliveira; Celso A Reis; Fátima Gärtner

    2015-01-01

    Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA0...

  10. Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis.

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    Takahiro Teshima

    Full Text Available Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD, which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1, which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2, which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX, an 11HSD inhibitor, on the healthy dog's pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH, and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing's disease.

  11. Mesenchymal stem cells with rhBMP-2 inhibits the growth of canine osteosarcoma cells

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    Grassi Rici Rose

    2012-02-01

    Full Text Available Abstract Background The bone morphogenetic proteins (BMPs belong to a unique group of proteins that includes the growth factor TGF-β. BMPs play important roles in cell differentiation, cell proliferation, and inhibition of cell growth. They also participate in the maturation of several cell types, depending on the microenvironment and interactions with other regulatory factors. Depending on their concentration gradient, the BMPs can attract various types of cells and act as chemotactic, mitogenic, or differentiation agents. BMPs can interfere with cell proliferation and the formation of cartilage and bone. In addition, BMPs can induce the differentiation of mesenchymal progenitor cells into various cell types, including chondroblasts and osteoblasts. The aim of this study was to analyze the effects of treatment with rhBMP-2 on the proliferation of canine mesenchymal stem cells (cMSCs and the tumor suppression properties of rhBMP-2 in canine osteocarcoma (OST cells. Osteosarcoma cell lines were isolated from biopsies and excisions of animals with osteosarcoma and were characterized by the Laboratory of Biochemistry and Biophysics, Butantan Institute. The mesenchymal stem cells were derived from the bone marrow of canine fetuses (cMSCs and belong to the University of São Paulo, College of Veterinary Medicine (FMVZ-USP stem cell bank. After expansion, the cells were cultured in a 12-well Transwell system; cells were treated with bone marrow mesenchymal stem cells associated with rhBMP2. Expression of the intracytoplasmic and nuclear markers such as Caspase-3, Bax, Bad, Bcl-2, Ki-67, p53, Oct3/4, Nanog, Stro-1 were performed by flow citometry. Results We evaluated the regenerative potential of in vitro treatment with rhBMP-2 and found that both osteogenic induction and tumor regression occur in stem cells from canine bone marrow. rhBMP-2 inhibits the proliferation capacity of OST cells by mechanisms of apoptosis and tumor suppression mediated by p

  12. Extrusion processing : effects on dry canine diets

    NARCIS (Netherlands)

    Tran, Q.D.

    2008-01-01

    Keywords: Extrusion, Canine diet, Protein, Lysine, Starch gelatinization, Palatability, Drying. Extrusion cooking is a useful and economical tool for processing animal feed. This high temperature, short time processing technology causes chemical and physical changes that alter the nutritional and

  13. Triple bone labeling of canine mandibles

    DEFF Research Database (Denmark)

    Pinholt, E M; Kwon, P H

    1990-01-01

    Fluorescence microscopy was used for evaluation of new bone formation in 16 canine mandibles augmented with hydroxylapatite (HA) granules. Three fluorochromes were injected at different time intervals during therapeutic radiation treatment. Oxytetracycline, DCAF, and alizarin-complexone were give...

  14. The relationship between basal and luminal cytokeratins with histopathologic characteristics of canine mammary gland cancer.

    Science.gov (United States)

    Eivani, D; Mortazavi, P

    2016-01-01

    Neoplasia occurs mostly in mammary glands in female dogs and mammary gland cancer is one of the causes of death in these animals cytokeratins are one of the most important of tumor markers for identification of tumor prognosis. In this study, 120 canine malignant tumor samples of mammary glands were studied. From each sample, a section was taken for hematoxylin-eosin staining and two sections for immunohistochemical staining of markers CK5/6 and CK7. Histopathology slides was evaluated by light microscope. The results show that the presence of markers CK7 and CK5/6 had no significant relationship with tumor grade and type (pmammary gland tumors. PMID:27487499

  15. Canine babesiosis: from molecular taxonomy to control

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    Irwin Peter J

    2009-03-01

    Full Text Available Abstract Canine babesiosis is a clinically significant emerging vector-borne disease caused by protozoan haemoparasites. This review article considers recent literature pertaining to the taxonomic classification of Babesia and Theileria species affecting dogs and the geographical distribution of these parasites. The diagnosis of canine babesiosis by traditional, molecular and serological methods is reviewed, together with recent advances in our understanding of the pathophysiology of piroplasmosis, and of the treatment and prevention of this disease.

  16. [Nonsurgical endodontic treatment of an invaginated canine].

    Science.gov (United States)

    Fernández Guerrero, F; Miñana Laliga, R; Bullon Fernandez, P

    1989-01-01

    We present a case of a maxillary canine with a dens invaginatus treated successfully. The patient had pain, swelling and a sinus tract coming from the inmature apex of the canine. The canals were enlarged and cleaned and the main canal was filled with Calcium Hydroxide to allow the root development. Seven months later, the patient was asymptomatic and the tooth was obturated with guttapercha. One year later it was confirm the success in the treatment. PMID:2638021

  17. Systemic inflammarory response in canine pyometra

    OpenAIRE

    Fransson, Boel

    2003-01-01

    Research efforts have focused mainly on the hormonal aspects of canine pyometra for more than 6 decades. However, this disease is often manifested as systemic illness in response to the bacterial uterine infection. Studies I-II were undertaken to clarify bacteriological aspects of canine pyometra; i.e. the origin of the infecting bacteria, the infecting bacteria’s impact on severity of the systemic illness and the presence of bacterial endotoxin in the systemic circulation. Study I, a bacteri...

  18. [Nonsurgical endodontic treatment of an invaginated canine].

    Science.gov (United States)

    Fernández Guerrero, F; Miñana Laliga, R; Bullon Fernandez, P

    1989-01-01

    We present a case of a maxillary canine with a dens invaginatus treated successfully. The patient had pain, swelling and a sinus tract coming from the inmature apex of the canine. The canals were enlarged and cleaned and the main canal was filled with Calcium Hydroxide to allow the root development. Seven months later, the patient was asymptomatic and the tooth was obturated with guttapercha. One year later it was confirm the success in the treatment.

  19. Treatment modalities of palatal impacted canines

    OpenAIRE

    Dimova, Cena; Papakoca, Kiro; Ristoska, Sonja; Kovacevska, Ivona

    2012-01-01

    Introduction: The orthodontic treatment of impacted maxillary canine remains a challenge to today’s clinicians. The treatment of this clinical entity usually involves surgical exposure of the impacted tooth, followed by orthodontic traction to guide and align it into the dental arch. The impacted palatal canine requires a combination of both treatment modalities: orthodontic management and oral surgical treatment. Two types of approach are commonly used: simple exposure, or exposure with brac...

  20. Proliferative histiocytic disorders of canine skin.

    Science.gov (United States)

    Middleton, D J

    1997-06-01

    Proliferative histiocytic disorders of canine skin present a clinical spectrum from the innocuous self-limiting solitary dermal lesion of cutaneous histiocytoma, through the recurrent deep dermal nodules of cutaneous histiocytosis to the generally fatal condition of Bernese Mountain Dogs termed systemic histiocytosis, in which visceral involvement is commonly encountered. Immunocytochemical characterization of the constituent histiocytic cells and accompanying lymphoid infiltrate using canine species specific reagents has elucidated considerably the mechanism by which these conditions exhibit their various biologic behaviours.

  1. Central nervous system tumors: Radiologic pathologic correlation and diagnostic approach

    Directory of Open Access Journals (Sweden)

    Ishita Pant

    2015-01-01

    Full Text Available Objective: This study was conducted to formulate location-wise radiologic diagnostic algorithms and assess their concordance with the final histopathological diagnosis so as to evaluate their utility in a rural setting where only basic facilities are available. Materials and Methods: A retrospective analysis to assess the concordance of radiology (primarily MRI with final histopathology report was done. Based on the most common incidence of tumor location and basic radiology findings, diagnostic algorithms were prepared. Results: For supratentorial intraaxial parenchymal location concordance was seen in all high-grade astrocytomas, low- and high-grade oligodendrogliomas, metastatic tumors, primitive neuroectodermal tumors, high-grade ependymomas, neuronal and mixed neuro-glial tumors and tumors of hematopoietic system. Lowest concordance was seen in low-grade astrocytomas. In the supratentorial intraaxial ventricular location, agreement was observed in choroid plexus tumors, ependymomas, low-grade astrocytomas and meningiomas; in the supratentorial extraaxial location, except for the lack of concordance in the only case of metastatic tumor, concordance was observed in meningeal tumors, tumors of the sellar region, tumors of cranial and paraspinal nerves; the infratentorial intraaxial parenchymal location showed agreement in low- as well as high-grade astrocytomas, metastatic tumors, high-grade ependymoma, embryonal tumors and hematopoietic tumors; in the infratentorial intraaxial ventricular location, except for the lack of concordance in one case of low-grade astrocytoma and two cases of medulloblastomas, agreement was observed in low- and high-grade ependymoma; infratentorial extraaxial tumors showed complete agreement in all tumors of cranial and paraspinal nerves, meningiomas, and hematopoietic tumors. Conclusion: A location-based approach to central nervous system (CNS tumors is helpful in establishing an appropriate differential diagnosis.

  2. Despre babesioza canină

    Directory of Open Access Journals (Sweden)

    Andrei Nanu

    2016-06-01

    Full Text Available The objective of this bibliographic essay, addressed both to veterinary clinicians and researchers, is to bring to mind the disease in terms of etiology, clinical manifestations and therapeutic and prophylactic management, as well as to remind the issues arising from recent researches. Depending on the virulence of the parasite species, body's immune response and therapeutic management approached, the plateau of disease evolution can be quite wide - from a favorable prognosis to a lethal outcome of the animal. The complexity of the pathogenic mechanism in babesiosis is due to soluble parasite antigens (SPA which, according to recent studies, have been obtained in vitro and then used as immunological product in disease prevention. Producing a vaccine against canine babesiosis with parasite antigens of local strains could play an important role to prevent the clinical expression of this disease in Romania.

  3. Environmental contamination by canine geohelminths.

    Science.gov (United States)

    Traversa, Donato; Frangipane di Regalbono, Antonio; Di Cesare, Angela; La Torre, Francesco; Drake, Jason; Pietrobelli, Mario

    2014-01-01

    Intestinal nematodes affecting dogs, i.e. roundworms, hookworms and whipworms, have a relevant health-risk impact for animals and, for most of them, for human beings. Both dogs and humans are typically infected by ingesting infective stages, (i.e. larvated eggs or larvae) present in the environment. The existence of a high rate of soil and grass contamination with infective parasitic elements has been demonstrated worldwide in leisure, recreational, public and urban areas, i.e. parks, green areas, bicycle paths, city squares, playgrounds, sandpits, beaches. This review discusses the epidemiological and sanitary importance of faecal pollution with canine intestinal parasites in urban environments and the integrated approaches useful to minimize the risk of infection in different settings. PMID:24524656

  4. Biomarkers in canine parvovirus enteritis.

    Science.gov (United States)

    Schoeman, J P; Goddard, A; Leisewitz, A L

    2013-07-01

    Canine parvovirus (CPV) enteritis has, since its emergence in 1978, remained a common and important cause of morbidity and mortality in young dogs. The continued incidence of parvoviral enteritis is partly due to the virus' capability to evolve into more virulent and resistant variants with significant local gastrointestinal and systemic inflammatory sequelae. This paper reviews current knowledge on historical-, signalment-, and clinical factors as well as several haematological-, biochemical- and endocrine parameters that can be used as diagnostic and prognostic biomarkers in CPV enteritis. These factors include season of presentation, purebred nature, bodyweight, vomiting, leukopaenia, lymphopaenia, thrombocytopaenia, hypercoagulability, hypercortisolaemia, hypothyroxinaemia, hypoalbuminaemia, elevated C-reactive protein and tumour necrosis factor, hypocholesterolaemia and hypocitrullinaemia. Factors contributing to the manifestations of CPV infection are multiple with elements of host, pathogen, secondary infections, underlying stressors and environment affecting severity and outcome. The availability of several prognosticators has made identification of patients at high risk of death and their subsequent targeted management more rewarding.

  5. CANINE: a robotic mine dog

    Science.gov (United States)

    Stancil, Brian A.; Hyams, Jeffrey; Shelley, Jordan; Babu, Kartik; Badino, Hernán.; Bansal, Aayush; Huber, Daniel; Batavia, Parag

    2013-01-01

    Neya Systems, LLC competed in the CANINE program sponsored by the U.S. Army Tank Automotive Research Development and Engineering Center (TARDEC) which culminated in a competition held at Fort Benning as part of the 2012 Robotics Rodeo. As part of this program, we developed a robot with the capability to learn and recognize the appearance of target objects, conduct an area search amid distractor objects and obstacles, and relocate the target object in the same way that Mine dogs and Sentry dogs are used within military contexts for exploration and threat detection. Neya teamed with the Robotics Institute at Carnegie Mellon University to develop vision-based solutions for probabilistic target learning and recognition. In addition, we used a Mission Planning and Management System (MPMS) to orchestrate complex search and retrieval tasks using a general set of modular autonomous services relating to robot mobility, perception and grasping.

  6. A new method for rapid Canine retraction

    Directory of Open Access Journals (Sweden)

    "Khavari A

    2001-06-01

    Full Text Available Distraction osteogenesis method (Do in bone lengthening and rapid midpalatal expansion have shown the great ability of osteognic tissues for rapid bone formation under distraction force and special protocol with optimum rate of one millimeter per day. Periodontal membrane of teeth (PDM is the extension of periostium in the alveolar socked. Orthodontic force distracts PDM fibers in the tension side and then bone formation will begin.Objects: Rapid retraction of canine tooth into extraction space of first premolar by DO protocol in order to show the ability of the PDM in rapid bone formation. The other objective was reducing total orthodontic treatment time of extraction cases.Patients and Methods: Tweleve maxillary canines in six patients were retracted rapidly in three weeks by a custom-made tooth-born appliance. Radiographic records were taken to evaluate the effects of heavy applied force on canine and anchorage teeth.Results: Average retraction was 7.05 mm in three weeks (2.35 mm/week. Canines rotated distal- in by mean 3.5 degrees.Anchorage loss was from 0 to 0.8 mm with average of 0.3 mm.Root resorption of canines was negligible, and was not significant clinically. Periodontium was normal after rapid retraction. No hazard for pulp vitality was observed.Discussion: PDM responded well to heavy distraction force by Do protocol. Rapid canine retraction seems to be a safe method and can considerabely reduce orthodontic time.

  7. Gene expression alterations during HGF-induced dedifferentiation of a renal tubular epithelial cell line (MDCK) using a novel canine DNA microarray.

    Science.gov (United States)

    Balkovetz, Daniel F; Gerrard, Edward R; Li, Shixiong; Johnson, David; Lee, James; Tobias, John W; Rogers, Katherine K; Snyder, Richard W; Lipschutz, Joshua H

    2004-04-01

    Hepatocyte growth factor (HGF) elicits a broad spectrum of biological activities, including epithelial cell dedifferentiation. One of the most widely used and best-studied polarized epithelial cell lines is the Madin-Darby canine kidney (MDCK) cell line. Here, we describe and validate the early response of polarized monolayers of MDCK cells stimulated with recombinant HGF using a novel canine DNA microarray designed to query 12,473 gene sequences. In our survey, eight genes previously implicated in the HGF signaling pathway were differentially regulated, demonstrating that the system was responsive to HGF. Also identified were 117 genes not previously known to be involved in the HGF pathway. The results were confirmed by real-time PCR or Western blot analysis for 38 genes. Of particular interest were the large number of differentially regulated genes encoding small GTPases, proteins involved in endoplasmic reticulum translation, proteins involved in the cytoskeleton, the extracellular matrix, and the hematopoietic and prostaglandin systems.

  8. Hematopoietic Stem Cell–Derived Cancer–Associated Fibroblasts Are Novel Contributors to the Pro-Tumorigenic Microenvironment

    Directory of Open Access Journals (Sweden)

    Lindsay T. McDonald

    2015-05-01

    Full Text Available Targeting the tumor microenvironment is critical toward improving the effectiveness of cancer therapeutics. Cancer-associated fibroblasts (CAFs are one of the most abundant cell types of the tumor microenvironment, playing an important role in tumor progression. Multiple origins for CAFs have been proposed including resident fibroblasts, adipocytes, and bone marrow. Our laboratory previously identified a novel hematopoietic stem cell (HSC origin for CAFs; however, the functional roles of HSC-derived CAFs (HSC-CAFs in tumor progression have not yet been examined. To test the hypothesis that HSC-CAFs promote tumor progression through contribution to extracellular matrix (ECM and paracrine production of pro-angiogenic factors, we developed a method to isolate HSC-CAFs. HSC-CAFs were profiled on the basis of their expression of hematopoietic and fibroblastic markers in two murine tumor models. Profiling revealed production of factors associated with ECM deposition and remodeling. Functional in vivo studies showed that co-injection of HSC-CAFs with tumor cells resulted in increased tumor growth rate and significantly larger tumors than tumor cells alone. Immunohistochemical studies revealed increased blood vessel density with co-injection, demonstrating a role for HSC-CAFs in tumor vascularization. Mechanistic in vitro studies indicated that HSC-CAFs play a role in producing vascular endothelial growth factor A and transforming growth factor–β1 in endothelial tube formation and patterning. In vitro and in vivo findings suggest that HSC-CAFs are a critical component of the tumor microenvironment and suggest that targeting the novel HSC-CAF may be a promising therapeutic strategy.

  9. Three-dimensional canine loop for management of buccally erupted canines

    Directory of Open Access Journals (Sweden)

    Praveen Mehrotra

    2015-01-01

    Full Text Available Maxillary canines are known as the cornerstones of mouth. They are considered to be important for esthetics and for functional occlusion. Any disturbance in the eruption process leading to an aberrant position will hamper esthetics as well as function. Orthodontic tooth movement of total buccally blocked-out canine is usually difficult as it is related with the problems of severe crowding, midline deviation, involvement of long root movement and risk of gingival recession. Such conditions can be treated orthodontically in various ways, but this clinical innovation helps to correct the buccally placed canines into the arch with a precise control of the canine in all the Three-dimensions (3D of space as well as providing maximum comfort to the patient by placing the canine loop on the palatal surface of the tooth, reducing soreness on the labial mucosa. It can be easily fabricated and activated at chairside for either simultaneous or sequential control in 3D.

  10. Emprego do cell block de agarose como método complementar no diagnóstico citológico de tumores mamários caninos Employment of cell block of agarose as additional method in the cytological diagnosis of canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Diogo Sousa Zanoni

    2013-03-01

    Full Text Available Os tumores mamários são neoplasias comuns em diversas espécies, sendo os processos oncológicos de maior incidência em cães. A elevada frequência e agressividade desses processos justificam a busca de métodos diagnósticos e prognósticos rápidos, de custo reduzido e menor invasividade, visando a uma abordagem cirúrgica e terapêutica adequada. O presente estudo avaliou a adequação da utilização da técnica de cell block de agarose como método diagnóstico complementar aos esfregaços tradicionais no diagnóstico desses processos. Para tanto, foram obtidas 51 amostras citológicas de tumores mamários de 30 cadelas que passaram por excisão tumoral no HOVET-UMESP, comparando-se os resultados obtidos a partir dos esfregaços, de cell blocks, e de sua associação (esfregaços cell blocks-1 com o diagnóstico histopatológico. Os melhores resultados foram obtidos mediante a associação dos métodos, reduzindo os resultados falso-negativos e elevando a correlação cito-histológica, reforçando a importância da citologia na rotina oncológica veterinária.The breast tumors are common neoplasms in several species, with high incidence in dogs. The high frequency and aggressiveness of these cases justifies the search for rapid, low cost and less invasive diagnostic methods, seeking for surgical approach and appropriate therapy. This study evaluated the appropriateness of the use of the agarose cell block technique as a diagnostic tool to complement traditional smears in the diagnosis of these processes. Therefore, it was obtained 51 samples from 30 dogs with breast tumors that underwent tumoral excision at the HOVET-UMESP, comparing the results obtained from smears, cell blocks, alone and in association (smears cell blocks-1, with the histopathologic diagnosis. The best results were obtained with the association of smears and cell block analysis, reducing the false negative results and increasing the cyto-histological correlation

  11. Calcification of multipotent prostate tumor endothelium.

    Science.gov (United States)

    Dudley, Andrew C; Khan, Zia A; Shih, Shou-Ching; Kang, Soo-Young; Zwaans, Bernadette M M; Bischoff, Joyce; Klagsbrun, Michael

    2008-09-01

    Solid tumors require new blood vessels for growth and metastasis, yet the biology of tumor-specific endothelial cells is poorly understood. We have isolated tumor endothelial cells from mice that spontaneously develop prostate tumors. Clonal populations of tumor endothelial cells expressed hematopoietic and mesenchymal stem cell markers and differentiated to form cartilage- and bone-like tissues. Chondrogenic differentiation was accompanied by an upregulation of cartilage-specific col2a1 and sox9, whereas osteocalcin and the metastasis marker osteopontin were upregulated during osteogenic differentiation. In human and mouse prostate tumors, ectopic vascular calcification was predominately luminal and colocalized with the endothelial marker CD31. Thus, prostate tumor endothelial cells are atypically multipotent and can undergo a mesenchymal-like transition.

  12. Immunoselection techniques in hematopoietic stem cell transplantation.

    Science.gov (United States)

    Li Pira, Giuseppina; Biagini, Simone; Cicchetti, Elisabetta; Merli, Pietro; Brescia, Letizia Pomponia; Milano, Giuseppe Maria; Montanari, Mauro

    2016-06-01

    Hematopoietic Stem Cells Transplantation (HSCT) is an effective treatment for hematological and non-hematological diseases. The main challenge in autologous HSCT is purging of malignant cells to prevent relapse. In allogeneic HSCT graft-versus-host disease (GvHD) and opportunistic infections are frequent complications. Two types of graft manipulation have been introduced: the first one in the autologous context aimed at separating malignant cells from hematopoietic stem cells (HSC), and the second one in allogeneic HSCT aimed at reducing the incidence of GvHD and at accelerating immune reconstitution. Here we describe the manipulations used for cell purging in autologous HSCT or for T Cell Depletion (TCD) and T cell selection in allogeneic HSCT. More complex manipulations, requiring a Good Manufacturing Practice (GMP) facility, are briefly mentioned. PMID:27209628

  13. Recent advances in hematopoietic stem cell biology

    DEFF Research Database (Denmark)

    Bonde, Jesper; Hess, David A; Nolta, Jan A

    2004-01-01

    made recently in the field of stem cell biology, researchers now have improved tools to define novel populations of stem cells, examine them ex vivo using conditions that promote self-renewal, track them into recipients, and determine whether they can contribute to the repair of damaged tissues......PURPOSE OF REVIEW: Exciting advances have been made in the field of hematopoietic stem cell biology during the past year. This review summarizes recent progress in the identification, culture, and in vivo tracking of hematopoietic stem cells. RECENT FINDINGS: The roles of Wnt and Notch proteins...... in regulating stem cell renewal in the microenvironment, and how these molecules can be exploited in ex vivo stem cell culture, are reviewed. The importance of identification of stem cells using functional as well as phenotypic markers is discussed. The novel field of nanotechnology is then discussed...

  14. Proteomic cornerstones of hematopoietic stem cell differentiation

    DEFF Research Database (Denmark)

    Klimmeck, Daniel; Hansson, Jenny; Raffel, Simon;

    2012-01-01

    Regenerative tissues such as the skin epidermis, the intestinal mucosa or the hematopoietic system are organized in a hierarchical manner with stem cells building the top of this hierarchy. Somatic stem cells harbor the highest self-renewal activity and generate a series of multipotent progenitors...... which differentiate into lineage committed progenitors and subsequently mature cells. In this report, we applied an in-depth quantitative proteomic approach to analyze and compare the full proteomes of ex vivo isolated and FACS-sorted populations highly enriched for either multipotent hematopoietic stem....../progenitor cells (HSPCs, Lin(neg)Sca-1(+)c-Kit(+)) or myeloid committed precursors (Lin(neg)Sca-1(-)c-Kit(+)). By employing stable isotope dimethyl labeling and high-resolution mass spectrometry, more than 5,000 proteins were quantified. From biological triplicate experiments subjected to rigorous statistical...

  15. Exogenous endothelial cells as accelerators of hematopoietic reconstitution

    Directory of Open Access Journals (Sweden)

    Mizer J

    2012-11-01

    Full Text Available Abstract Despite the successes of recombinant hematopoietic-stimulatory factors at accelerating bone marrow reconstitution and shortening the neutropenic period post-transplantation, significant challenges remain such as cost, inability to reconstitute thrombocytic lineages, and lack of efficacy in conditions such as aplastic anemia. A possible means of accelerating hematopoietic reconstitution would be administration of cells capable of secreting hematopoietic growth factors. Advantages of this approach would include: a ability to regulate secretion of cytokines based on biological need; b long term, localized production of growth factors, alleviating need for systemic administration of factors that possess unintended adverse effects; and c potential to actively repair the hematopoietic stem cell niche. Here we overview the field of hematopoietic growth factors, discuss previous experiences with mesenchymal stem cells (MSC in accelerating hematopoiesis, and conclude by putting forth the rationale of utilizing exogenous endothelial cells as a novel cellular therapy for acceleration of hematopoietic recovery.

  16. Change in Erythropoietin Pharmacokinetics Following Hematopoietic Transplantation

    OpenAIRE

    Widness, JA; Schmidt, RL; Hohl, RJ; Goldman, FD; Al-Huniti, NH; Freise, KJ; Veng-Pedersen, P.

    2007-01-01

    Pre-clinical studies have demonstrated that bone marrow ablation has a profound effect in decreasing erythropoietin (EPO) elimination. The study’s objective was to determine in humans if EPO pharmacokinetics (PKs) are perturbed following bone marrow ablation. EPO PK studies were performed in eight subjects, aged 4 to 61 years, undergoing fully myeloablative hematopoietic stem cell transplantation. Serial PK studies using intravenous injection of recombinant human EPO (92±2.0 U/kg) (mean±SEM) ...

  17. Autologous tumor cell lysate-loaded dendritic cells and cytokine-induced killer cells in combination with autologous hematopoietic stem cell transplatation in the treatment of refractory lymphoma%负载自体肿瘤抗原的DC-CIK细胞联合自体造血干细胞移植治疗难治性淋巴瘤的临床研究

    Institute of Scientific and Technical Information of China (English)

    苏毅; 邵文军; 闵敏; 李莉; 陈健; 范方教; 易海; 付利; 刘阳阳; 邓涛; 孙浩平; 孙薏; 钟国成

    2009-01-01

    目的 观察负载自体肿瘤抗原的DE-CIK细胞联合自体造血干细胞移植治疗难治性淋巴瘤的疗效.方法 选取难治性淋巴瘤35例,采用MAC预处理方案,用自体淋巴瘤抗原致敏DC-CIK细胞,于移植预处理后5-10d,将DC-CIK细胞回输给患者.结果 35例难治性淋巴瘤中,29例完全缓解(82.86%),4例部分缓解(14.43%),移植过程中死亡2例(5.71%)(均死于严重混合性感染).所有完全缓解和部分缓解病例均随访3-49个月:4名部分缓解患者分别于移植后3、6、10、13个月后病情进展死亡;完全缓解患者中有3人于移植后11、17、20个月再次复发死亡;现存活26例.结论 负载自体肿瘤抗原的DC-CIK细胞联合自体造血千细胞移植治疗难治性淋巴瘤高于单纯自体外周血造血干细胞的疗效,且无明显毒副作用.%Objective To study the efficacy and side effect of autologons tumor cell lysate-loaded DC-CIK plus autologous hematopoietic stem cell transplantation in the treatment of refractory lymphoma.Methods Thirty-five cases of refractory lymphoma were recruited,lymphoma antigen-pulsed autologous DE-CIK cells were infused 5-10 days after the MAC conditioning regimen.Results Out of the 35 Cases,complete remission Was achieved in 29(82.8%),partial remission in 4(14.4%).Two patients died during transplantation due to severe mixed infections,with a transplant-related mortality rate of 5.7%.All cases of complete remission and partial remission were followed-up for 3-49 months,4 cases with partial remission died 3,6,10,13 months after transplantation.Three cases with complete remission relapsed 11,17,20 months after transplantation.and the other 26 cases survived until now.Conclusion Autologous tumor cell lysate-loaded DE-CIK combined with autologous hematopoietic stem cell transplantation in the treatment of refractory lymphoma is safe and effective.

  18. Genotoxic sensitivity of the developing hematopoietic system.

    Science.gov (United States)

    Udroiu, Ion; Sgura, Antonella

    2016-01-01

    Genotoxic sensitivity seems to vary during ontogenetic development. Animal studies have shown that the spontaneous mutation rate is higher during pregnancy and infancy than in adulthood. Human and animal studies have found higher levels of DNA damage and mutations induced by mutagens in fetuses/newborns than in adults. This greater susceptibility could be due to reduced DNA repair capacity. In fact, several studies indicated that some DNA repair pathways seem to be deficient during ontogenesis. This has been demonstrated also in murine hematopoietic stem cells. Genotoxicity in the hematopoietic system has been widely studied for several reasons: it is easy to assess, deals with populations cycling also in the adults and may be relevant for leukemogenesis. Reviewing the literature concerning the application of the micronucleus test (a validated assay to assess genotoxicity) in fetus/newborns and adults, we found that the former show almost always higher values than the latter, both in animals treated with genotoxic substances and in those untreated. Therefore, we draw the conclusion that the genotoxic sensitivity of the hematopoietic system is more pronounced during fetal life and decreases during ontogenic development. PMID:27036061

  19. Prostaglandin E2 regulates hematopoietic stem cell

    International Nuclear Information System (INIS)

    Prostaglandin E2 (PGE2) is a bioactive lipid molecule produced by cyclooxygenase (COX), which plays an important role on hematopoiesis. While it can block differentiation of myeloid progenitors but enhance proliferation of erythroid progenitors. Recent research found that PGE2 have the effects on hematopoietic stem cell (HSC) function and these effects were independent from effects on progenitor cells. Exposure of HSC cells to PGE2 in vitro can increase homing efficiency of HSC to the murine bone marrow compartment and decrease HSC apoptosis, meanwhile increase long-term stem cell engraftment. In-vivo treatment with PGE2 expands short-term HSC and engraftment in murine bone marrow but not long-term HSC.In addition, PGE2 increases HSC survival after radiation injury and enhance hematopoietic recovery, resulting maintains hematopoietic homeostasis. PGE2 regulates HSC homeostasis by reactive oxygen species and Wnt pathway. Clinical beneficial of 16, 16-dimethyl-prostaglandin E2 treatment to enhance engraftment of umbilical cord blood suggest important improvements to therapeutic strategies. (authors)

  20. Canine distemper virus detection in asymptomatic and non vaccinated dogs

    OpenAIRE

    Del Puerto, Helen L; Vasconcelos, Anilton C.; Luciana Moro; Fabiana Alves; Braz, Gissandra F; Almir S. Martins

    2010-01-01

    A quantitative real time polymerase chain reaction (PCR) revealed canine distemper virus presence in peripheral blood samples from asymptomatic and non vaccinated dogs. Samples from eleven domestic dogs with no signs of canine distemper and not vaccinated at the month of collection were used. Canine distemper virus vaccine samples in VERO cells were used as positive controls. RNA was isolated with Trizol®, and treated with a TURBO DNA-free kit. Primers were designed for canine distemper virus...

  1. Selenium supplementation in patients undergoing hematopoietic stem cell transplantation: effects on pro-inflammatory cytokines levels

    OpenAIRE

    Daeian, Nesa; Radfar, Mania; Jahangard-Rafsanjani, Zahra; Hadjibabaie, Molouk; Ghavamzadeh, Ardeshir

    2014-01-01

    Background Pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) play an important role in the development of hematopoietic stem cell transplantation (HSCT) complications. We explored the effect of Selenium as an antioxidant and anti-inflammatory agent on pro-inflammatory cytokines levels in HSCT candidates. Findings Plasma concentrations of TNF-α, IL-1β and IL-6 were measured in 74 patients from a double-blind, randomized, p...

  2. Constitutive phosphorylation of the mTORC2/Akt/4E-BP1 pathway in newly derived canine hemangiosarcoma cell lines

    Directory of Open Access Journals (Sweden)

    Murai Atsuko

    2012-07-01

    Full Text Available Abstract Background Canine hemangiosarcoma (HSA is a malignant tumor with poor long-term prognosis due to development of metastasis despite aggressive treatment. The phosphatidyl-inositol-3 kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR pathway is involved in its endothelial pathologies; however, it remains unknown how this pathway plays a role in canine HSA. Here, we characterized new canine HSA cell lines derived from nude mice-xenografted canine HSAs and investigated the deregulation of the signaling pathways in these cell lines. Results Seven canine HSA cell lines were established from 3 xenograft canine HSAs and showed characteristics of endothelial cells (ECs, that is, uptake of acetylated low-density lipoprotein and expression of canine-specific CD31 mRNA. They showed varied morphologies and mRNA expression levels for VEGF-A, bFGF, HGF, IGF-I, EGF, PDGF-B, and their receptors. Cell proliferation was stimulated by these growth factors and fetal bovine serum (FBS in 1 cell line and by FBS alone in 3 cell lines. However, cell proliferation was not stimulated by growth factors and FBS in the remaining 3 cell lines. Phosphorylated p44/42 Erk1/2 was increased by FBS stimulation in 4 cell lines. In contrast, phosphorylation of Akt at Ser473, mTOR complex 1 (mTORC1 at Ser2448, and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1 at Ser65 was high in serum-starved condition and not altered by FBS stimulation in 6 cell lines, despite increased phosphorylation of these residues in normal canine ECs. This suggested that the mTORC2/Akt/4E-BP1 pathway was constitutively activated in these 6 canine HSA cell lines. After cell inoculation into nude mice, canine HSA tumors were formed from 4 cell lines and showed Akt and 4E-BP1 phosphorylation identical to the parental cell lines. Conclusions Our findings suggest that the present cell lines may be useful tools for investigating the role of the mTORC2/Akt/4E-BP1 pathway in

  3. Elevated Krüppel-like factor 4 transcription factor in canine mammary carcinoma

    Directory of Open Access Journals (Sweden)

    Yeh Kun-Tu

    2011-10-01

    Full Text Available Abstract Background Krüppel-like factors (KLFs are critical regulators of biological and physiological systems and have been extensively studied for their roles in cell proliferation, differentiation and survival in the context of cancer. Among the KLFs, KLF4 is highly expressed in human breast cancers and plays an oncogenic role. The present study examined the expression of KLF4 and assessed its significance in canine mammary carcinoma. Results Immunohistochemistry was employed to investigate the expression of KLF4 in 142 cases of canine mammary tumor. 75 of the 142 (52.8% cases were histologically confirmed as mammary carcinoma. Quantification of immunohistochemistry was carried out using Quick score which multiply the staining intensity by the percentage of positive cells. High KLF4 expression was identified in 44 of the 75 (59% dogs with mammary carcinoma and none in the benign cases. High KLF4 expression occurred only in the tumor cells and not the adjacent normal cells in mammary carcinoma (P Conclusions KLF4 is highly and frequently expressed in canine mammary carcinoma and correlates with a more aggressive phenotype.

  4. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper...

  5. Canine hypothyroidism. A diagnostic challenge?

    International Nuclear Information System (INIS)

    Hypothyroidism is one of the most common endocrinopathies in dogs. Clinical symptoms and hematological and biochemical parameters lead to a first suspicion. To confirm diagnosis can be challenging, however. Determination of total serum T4 concentration is accepted as the primary screening test for the disease, and low serum T4 concentrations are intuitively suggestive of hypothyroidism. However it is well known that low T4 concentrations are frequently encountered in euthyroid dogs with various nonthyroidal diseases and in dogs receiving certain pharmacologic agents. Since assessment of endogenous TSH (canine TSH) using current canine TSH assays shows normal values in a high percentage of hypothyroid dogs (up to 40%), its diagnostic value is only limited. The TSH-stimulation test can still be recognized as the gold standard for the diagnosis of hypothyroidism in dogs. Determination of circulating T4 concentration before and 6 hours after the administration of exogenous TSH (recombinant human TSH, Thyrogen registered) provides an assessment of the functional reserve capacity of the thyroid gland with minimal change in post-TSH T4 concentration, compared with the basal concentration, expected in dogs with hypothyroidism. Also this test can be influenced by nonthyroidal illness and by medications known to affect thyroid function. This suppressing influence seems to be less pronounced using a higher dose of TSH. Therefore, to improve the discriminatory power of the TSH stimulation test to differentiate between euthyroid-sick and primary hypothyroidism, the higher dose should be used in cases in which testing cannot be delayed. More recently, ultrasonography and scintigraphy have been used for the diagnosis of primary hypothyroidism. Using ultrasonography, a sensitivity of 98% was reported if size and echogenicity of the gland were combined. However, specificity was as low as 77%. and care must be taken when measuring the gland because of a relatively high interobserver

  6. Establishment and characterization of a canine xenograft model of inflammatory mammary carcinoma.

    Science.gov (United States)

    Camacho, L; Peña, L; González Gil, A; Cáceres, S; Díez, L; Illera, J C

    2013-12-01

    Canine inflammatory mammary cancer (IMC) and human inflammatory breast cancer (IBC) are the most aggressive form of mammary/breast cancer. Both species naturally develop it, sharing epidemiological, clinical and histological characteristics. Thus, IMC has been suggested as a model to study the human disease. We have developed the first IMC xenograft model in SCID mice. Xenografts reproduced the histological features from the primary tumor, were highly aggressive and showed dermal tumor emboli, distinctive hallmarks of IMC/IBC. This model was hormone receptors positive and HER2 negative. Our findings showed that estrogens and androgens are locally produced in tissues. Factors related to tumor vascularization showed positive expression and xenografts with the highest expression of all analyzed vascular factors had the highest rate of tumor proliferation. The role of steroid hormones and the angio/lymphangiogenic properties found in this model, provide additional knowledge for future interventions in the diagnosis, treatment and prevention of the disease.

  7. Transmigration of mandibular canine – case report

    International Nuclear Information System (INIS)

    Transmigration is a phenomenon of movement of an unerupted tooth in the bone across the midline. This anomaly is not often found. Transmigration is more prevalent in females than in males, and more often encountered in the mandible than maxilla, it affects mostly canines. The aim of this study was to present a case report of a mandibular canine transmigration in a patient aged 12. Intraoral examination determined hypodontia of right second premolar and delayed eruption of left second premolar in maxilla, as well as persistent deciduous teeth: right second molar, left canine and second molar. The patient was referred for a Cone-Beam CT examination, which allowed precise visualization of the transmigrating canine as well as ruled out resorption of roots of mandibular incisors. The treatment with a maxillary fixed orthodontic appliance was finished after obtaining a satisfactory result. Proper alignment of the incisors in the anterior-posterior plane and correct midline position were accepted by the patient. Transmigrating canine after consultation with the surgeon was designed to further radiological observation

  8. Hematopoietic specification from human pluripotent stem cells: current advances and challenges toward de novo generation of hematopoietic stem cells.

    Science.gov (United States)

    Slukvin, Igor I

    2013-12-12

    Significant advances in cellular reprogramming technologies and hematopoietic differentiation from human pluripotent stem cells (hPSCs) have already enabled the routine production of multiple lineages of blood cells in vitro and opened novel opportunities to study hematopoietic development, model genetic blood diseases, and manufacture immunologically matched cells for transfusion and cancer immunotherapy. However, the generation of hematopoietic cells with robust and sustained multilineage engraftment has not been achieved. Here, we highlight the recent advances in understanding the molecular and cellular pathways leading to blood development from hPSCs and discuss potential approaches that can be taken to facilitate the development of technologies for de novo production of hematopoietic stem cells.

  9. Canine treatment with SnET2 for photodynamic therapy

    Science.gov (United States)

    Frazier, Donita L.; Milligan, Andrew J.; Vo-Dinh, Tuan; Morgan, Alan R.; Overholt, Bergein F.

    1990-07-01

    Photodynamic therapy is a treatment technique that utilizes the photoactived species of a drug to destroy tumor tissue. To be successful, the drug must localize in tumor tissue preferentially over normal tissue and must be activated by light of a specific wavelength. Currently the only drug to be approved for clinical use is Heinatoporphyrin Derivative (HpD) although a series of new drugs are being developed for use in the near future. One of the drugs belongs to a class called purpurins which display absorp-' tions between 630-711 nm. Along with several other investigators, we are currently exploring the characteristics of a specific purpurin (SnET2) in normal and tumorous canine tissue. The use of this compound has demonstrated increased tumor control rates in spontaneous dog tumors. Preliminary pharmacokinetic studies have been performed on 6 normal beagle dogs. SnET2 (2 mg/kg) was injected intravenously over 10 minutes and blood was collected at 5, 15, 30, 45 minutes and at 1, 2, 4, 8, 12 and 24 hours following administration for determination of drug concentration and calculation of pharinacokinetic parameters. Skin biopsies were collected at 1, 4, 8, 12 and 24 hours. Dogs were euthanized at 24 hours and tissues (liver, kidney muscle, esophagus, stomach, duodenum, jejunum, ileura, colon, adrenal gland, thyroid, heart, lung, urinary bladder, prostate, pancreas, eye, brain) were collected for drug raeasurement. Drug was shown to persist in liver and kidney for a prolonged period of time coiapared to other tissues. Knowledge of the pharmacokinetic properties of the drug will greatly add to the ability to treat patients with effective protocols.

  10. Composite mandibular allografts in canines

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To evaluate the feasibility of transplanting composite mandibular allografts to repair large mandibular defects. Methods: Three composite mandibular transplantation models were established. The first model consisted of hemimandible with the attached teeth, muscle and skin, and oral mucosa. The second model was transplanted in the same way with the first one excluding oral mucosa and some teeth, and third one excluding the oral mucosa and all dental crowns. Fourteen transplanting operations were performed in canines. Cyclosporine A and methylprednisone were given for immunosuppression. Results: The composite mandibular organs had an effective and closed return circuit. Transplantation of vascularized allograft of mandibular compound organs was feasible. Two longest time survivors of 67 d and 76 d were in the third model group. Cyclosporine A was successful in suppressing rejection of transplanted composite allograft and prolonging survival time of transplantation models. Conclusions: The composite mandibular allografts were available with large block of living composite tissue,and helpful in restoration of appearance and function for severe mandibular defects.

  11. Canine malignant peripheral nerve sheath tumor involving nerve roots of the third lumbar spinal cord segmentTumor maligno da bainha de nervo periférico envolvendo raízes nervosas do terceiro segmento medular lombar em um cão

    Directory of Open Access Journals (Sweden)

    Elisângela Olegário da Silva

    2012-12-01

    Full Text Available Malignant peripheral nerve sheath tumors (MPNST involving spinal nerve roots are uncommon in dogs. A nine-year old, intact, mixed-breed dog, demonstrated clinical signs of incoordination in the pelvic limbs and micturition for approximately one week. Clinical examination revealed proprioceptive deficits and bilateral patellar hyperreflexia. During exploratory celiotomy a mass was observed adhered to the lumbar vertebral segments. Medical therapy was initiated, but neurological signs were progressive, and the owner opted for euthanasia. Gross examination showed that the mass in the abdominal cavity was attached to the lumbar segments L3 and L4, causing bone lysis in L3, but showed no tumor invasion into the spinal canal. Microscopic features were characterized by prominent proliferation of ovoid and fusiform cells with poorly defined cytoplasm arranged in interlacing bundles and concentric whorls. The cells were embedded in a delicate to moderate collagenous stroma and moderate anisokariose and high mitotic activity were noted. The immunohistochemical assay showed positive staining for GFAP, S-100 protein and vimentin, and negative staining for factor VIII, ?-actin and citokeratine. The definitive diagnosis of malignant peripheral nerve sheath tumor was made on the basis of the histological and immunohistochemical findings. Tumores malignos da bainha de nervo periférico (TMBNP em raízes nervosas espinhais são incomuns em cães. Relata-se o caso de um cão, sem raça definida, nove anos de idade, não castrado, com histórico de incoordenação em membros pélvicos e retenção urinária há aproximadamente uma semana. Ao exame clínico constatou-se déficit proprioceptivo e hiperreflexia patelar bilaterais. Durante a celiotomia exploratória constatou-se uma massa intensamente vascularizada e aderida aos segmentos vertebrais lombares. Estabeleceu-se plano terapêutico e o animal foi tratado com fluidoterapia, anti-inflamatório e analg

  12. Human Placenta Is a Potent Hematopoietic Niche Containing Hematopoietic Stem and Progenitor Cells throughout Development

    NARCIS (Netherlands)

    C. Robin (Catherine); K. Bollerot (Karine); S.C. Mendes (Sandra); E. Haak (Esther); M. Crisan (Mihaela); F. Cerisoli (Francesco); I. Lauw (Ivoune); P. Kaimakis (Polynikis); R.J.J. Jorna (Ruud); M. Vermeulen (Mark); M.H. Kayser (Manfred); R. van der Linden (Reinier); P. Imanirad (Parisa); M.M.A. Verstegen (Monique); H. Nawaz-Yousaf (Humaira); N. Papazian (Natalie); E.A.P. Steegers (Eric); T. Cupedo (Tom); E.A. Dzierzak (Elaine)

    2009-01-01

    textabstractHematopoietic stem cells (HSCs) are responsible for the life-long production of the blood system and are pivotal cells in hematologic transplantation therapies. During mouse and human development, the first HSCs are produced in the aorta-gonad-mesonephros region. Subsequent to this emerg

  13. Polycomb-group proteins in hematopoietic stem cell regulation and hematopoietic neoplasms

    NARCIS (Netherlands)

    Radulovic, V.; de Haan, G.; Klauke, K.

    2013-01-01

    The equilibrium between self-renewal and differentiation of hematopoietic stem cells is regulated by epigenetic mechanisms. In particular, Polycomb-group (PcG) proteins have been shown to be involved in this process by repressing genes involved in cell-cycle regulation and differentiation. PcGs are

  14. Canine and feline nasal neoplasia.

    Science.gov (United States)

    Malinowski, Christine

    2006-05-01

    Dogs and cats of our society have outgrown their status as merely pets and are now considered our close companions and even family members. This shift in their roles has led to pet owners seeking improved preventative medicine for their four-legged friends. Subsequently, dogs and cats are living longer lives than ever before and developing more old-age-related diseases. One of the most devastating diseases of older animals is cancer. Once a veterinarian has detected cancer in a pet, pet owners seek advice on their next course of action. This article is intended to provide concise information regarding the diagnosis and treatment of intranasal tumors of the dog and cat. This article outlines the forms of nasal tumors that are the most common, the recommended imaging and biopsy techniques to diagnose the tumor, and the most appropriate treatments of them. PMID:16711615

  15. Evolving concepts on the microenvironmental niche for hematopoietic stem cells.

    NARCIS (Netherlands)

    Raaijmakers, M.G.P.; Scadden, D.T.

    2008-01-01

    PURPOSE OF REVIEW: The hematopoietic stem cell niche is critical for the maintenance and proliferation of hematopoietic stem cells and, as such, is not only essential for steady-state hematopoiesis but may also be relevant to hematologic disease. The present review discusses recent advances in the u

  16. Binding of VEGF-A to canine cancer cells with preferential expression of VEGFR1

    Directory of Open Access Journals (Sweden)

    Antonella Borgatti,

    2014-01-01

    Full Text Available Aim: Despite encouraging results in syngeneic and xenografts cancer models with various inhibitors of vascular endothelial growth factor (VEGF or its receptors (VEGFRs, beneficial effects have not been consistently translated to the clinic, underscoring the need to develop strategies that go beyond the inhibition of these targets. The purpose of this study was to generate data to support the hypothesis that VEGF may be used as “bait” to selectively deliver therapeutics to VEGFR-expressing cancer cells. Materials and Methods: VEGFR1 and VEGFR2 expression was characterized using real time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR in canine hemangiosarcoma (Grace-HSA, Emma-HSA, melanoma (TLM-1, and thyroid adenocarcinoma (CTAC cell lines. TLM-1 and Grace-HSA were identified as representative cell lines that selectively expressed high levels of VEGFR1. Flow cytometry was performed to examine binding of a single VEGF molecule (biotinylated VEGFA and avidin conjugated to fluorescein isothiocyanate (FITC by these chemoresistant cell lines. Results: RT-qPCR showed that canine tumor cells can preferentially express VEGFR1 over VEGFR2. Both TLM-1 and Grace-HSA cell lines, which represent VEGFR1-expressing tumors, showed specific binding to VEGF-A and this binding was competitively inhibited by anti-VEGF antibody. Conclusions: Cells preferentially expressing VEGFR1 can be targeted with a single VEGF molecule and these ligand-receptor pairs are well suited for targeting cytotoxic molecules in various canine tumor cells. Further studies are needed to develop strategies to selectively deliver therapeutics through VEGF-VEGFRs binding into VEGFR-expressing tumors.

  17. Treatment of pulmonary metastatic tumors in mice using lentiviral vector-engineered stem cells

    OpenAIRE

    Zhang, X.; Zhao, P; Kennedy, C; Chen, K.; Wiegand, J; Washington, G; Marrero, L; Cui, Y.

    2007-01-01

    Active cancer immunotherapy relies on functional tumor-specific effector T lymphocytes for tumor elimination. Dendritic cells (DCs), as most potent antigen-presenting cells, have been popularly employed in clinical and experimental tumor treatments. We have previously demonstrated that lentiviral vector-mediated transgene delivery to DC progenitors, including bone marrow cells and hematopoietic stem cells, followed by transplantation supports systemic generation of great numbers of tumor anti...

  18. Tooth fractures in canine clinical practice

    International Nuclear Information System (INIS)

    Tooth fractures constitute a considerable fraction of all tooth diseases. Out of the 5,370 dogs treated during four years, 492 were presented with dental problems and 28.3 % of the latter were treated for tooth fractures. Canines were the most frequently affected teeth (38.8 %), followed by premolars (33.1 %), incisors (25.9 %), and molars (2.2 %), 55.4 % of the patients with canine and incisor fractures being large breed dogs. Fractures of premolars (mostly of 108, 208) were divided evenly irrespective of breed or body size. Nonsurgical endodontic treatment yielded good therapeutic results in most cases, but repeated treatment was necessary in some patients

  19. A Study of Transmigrated Canine in an Indian Population

    Science.gov (United States)

    Sharma, Gaurav; Nagpal, Archna

    2014-01-01

    Aim. The purpose of this study was to investigate the prevalence of transmigrated canines in a north Indian population and association with gender, side, associated pathologies, and dental anomalies. Subjects and methods. The prospective study consisted of panoramic radiographs of 3000 patients from two dental colleges in north India. The panoramic radiographs were screened for radiographically identified position of the transmigrated tooth, retained canine, and other coexisting dental anomalies. Results. The overall prevalence of transmigrated canines (15 mandibular and 5 maxillary) was 0.66%. The prevalence of mandibular transmigrated canine was 0.5% and maxillary transmigrated canine was 0.16%. All the transmigrated canines were unilateral. The age range was 15–53 years (average age 24.1 years) and there were 12 males (60%) and 8 females (40%). Type 1 mandibular canine transmigration was the commonest type found in our study (10 cases), followed by types 2 and 4 (2 cases each) and 1 case of type 5 transmigration. Conclusion. The prevalence of transmigrated canines in the north Indian population was 0.66% and no gender predilection was evident. The transmigrated canines have a low complication rate (10.0%) and no correlation with other dental anomalies was found. Type 3 canine is the rarest form of mandibular canine transmigration. PMID:27433532

  20. Hematopoietic potential cells in skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    Atsushi Asakura

    2007-01-01

    @@ During mouse embryogenesis,the formation of primi-tive hematopoiesis begins in the yolk sac on embryonic day 7.5(E7.5).Thereafter,definitive hematopoietic stem cell(HSC)activity is first detectable in the aorta-gonad-mesonephros(AGM)region on E10,followed by fetal liver and yolk sac.Subsequently,the fetal liver by E12 becomes the main tissue for definitive hematopoiesis.At a later time,HSC population in the fetal liver migrates to the bone marrow,which becomes the maior site of he-matopoiesis throughout normal adult life[1].

  1. Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times

    Directory of Open Access Journals (Sweden)

    Rao Nagesha AS

    2009-09-01

    Full Text Available Abstract Background Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS. Results The 32 tumors were classified into two prognostic groups based on survival time (ST. They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months and long survivors (dogs with better prognosis: surviving 6 months or longer. Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans. Conclusion A molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the

  2. WT1 Peptide Cancer Vaccine for Patients with Hematopoietic Malignancies and Solid Cancers

    Directory of Open Access Journals (Sweden)

    Yoshihiro Oka

    2007-01-01

    Full Text Available Wild-type Wilms' tumor gene WT1 is expressed at a high level in hematopoietic malignancies including acute leukemia, chronic myelogenous leukemia, and myelodysplastic syndromes, as well as in various kinds of solid cancers. Human cytotoxic T lymphocytes (CTLs, which could specifically lyse WT1-expressing tumor cells with HLA class I restriction, were generated in vitro. It was also demonstrated that mice immunized with the WT1 peptide rejected challenges by WT1-expressing cancer cells and survived with no signs of autoaggression to normal organs that physiologically expressed WT1. Furthermore, we and others detected IgM and IgG WT1 antibodies in patients with hematopoietic malignancies, indicating that the WT1 protein was highly immunogenic, and that immunoglobulin class-switch-inducing, WT1-specific, cellular immune responses were elicited in these patients. CD8+ WT1-specific CTLs were also detected in peripheral blood or tumor-draining lymph nodes of cancer patients. These results provided us with the rationale for elicitation of CTL responses targeting the WT1 product for cancer immunotherapy. On the basis of these findings, we performed a phase I clinical trial of a WT1 peptide cancer vaccine for the patients with malignant neoplasms. These results strongly suggested that the WT1 peptide cancer vaccine had efficacy in the clinical setting because clinical responses, including reduction of leukemic blast cells or regression of tumor masses, were observed after the WT1 vaccination in patients with hematopoietic malignancies or solid cancers. The power of a tumor-associated-antigen (TAA-derived cancer vaccine may be enhanced in combination with stronger adjuvants, helper peptide, molecular-target-based drugs, or some chemotherapy drugs, such as gemcitabine, which has been revealed to suppress regulartory T-cell function. In contrast, reduction of WT1 peptide dose may be needed for the treatment of patients with hematological stem cell diseases

  3. Epigenetic regulation of hematopoietic stem cell aging

    International Nuclear Information System (INIS)

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging

  4. Radiation response of human hematopoietic cells

    International Nuclear Information System (INIS)

    The radiosensitivity and capacity to accumulate and repair sub-lethal damage has been studied in hematopoietic cell lines of human origin and in stem cells derived from blood and bone narrow of normal human donors. The results were analysed in terms of the linear quadratic and multitarget models. For the cell lines intrinsic radiosensitivity varied widely with D/sub o/'s ranging from 0.53 to 1.39 Gy. Five of the cell lines showed same capacity to accumulate sub-lethal damage and in three of these survival was enhanced by dose fractionation or reduction of dose rate. Among the cell lines of leukemic origin, several did not conform in one or more respects with the highly radiosensitive and repair deficient model associated with hematopoietic cells. There was no apparent correlation between radiation response and the phenotype (myeloid, lymphoid or undifferentiated) of the cell lines studied. Variability of radiation response and in some cases an unpredicted degree of radioresistance and capacity to repair sub-lethal damage has now been demonstrated for both cultured and primary explants of human leukemic cells. These observations have implications for the design of Total Body Irradiation protocols for use prior to bone narrow transplant

  5. The biology of hematopoietic stem cells.

    Science.gov (United States)

    Szilvassy, Stephen J

    2003-01-01

    Rarely has so much interest from the lay public, government, biotechnology industry, and special interest groups been focused on the biology and clinical applications of a single type of human cell as is today on stem cells, the founder cells that sustain many, if not all, tissues and organs in the body. Granting organizations have increasingly targeted stem cells as high priority for funding, and it appears clear that the evolving field of tissue engineering and regenerative medicine will require as its underpinning a thorough understanding of the molecular regulation of stem cell proliferation, differentiation, self-renewal, and aging. Despite evidence suggesting that embryonic stem (ES) cells might represent a more potent regenerative reservoir than stem cells collected from adult tissues, ethical considerations have redirected attention upon primitive cells residing in the bone marrow, blood, brain, liver, muscle, and skin, from where they can be harvested with relative sociological impunity. Among these, it is arguably the stem and progenitor cells of the mammalian hematopoietic system that we know most about today, and their intense study in rodents and humans over the past 50 years has culminated in the identification of phenotypic and molecular genetic markers of lineage commitment and the development of functional assays that facilitate their quantitation and prospective isolation. This review focuses exclusively on the biology of hematopoietic stem cells (HSCs) and their immediate progeny. Nevertheless, many of the concepts established from their study can be considered fundamental tenets of an evolving stem cell paradigm applicable to many regenerating cellular systems. PMID:14734085

  6. Epigenetic regulation of hematopoietic stem cell aging

    Energy Technology Data Exchange (ETDEWEB)

    Beerman, Isabel, E-mail: isabel.beerman@childrens.harvard.edu [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States); Rossi, Derrick J. [Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 (United States); Department of Pediatrics, Harvard Medical School, Boston, MA 02115 (United States); Program in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children' s Hospital, MA 02116 (United States)

    2014-12-10

    Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks – DNA methylation and histone modifications – but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging.

  7. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  8. Experimental Forelimb Allotransplantation in Canine Model

    Science.gov (United States)

    2016-01-01

    As reconstructive transplantation is gaining popularity as a viable alternative for upper limb amputees, it is becoming increasingly important for plastic surgeons to renew surgical skills and knowledge of this area. Forelimb allotransplantation research has been performed previously in rodent and swine models. However, preclinical canine forelimb allotransplantation studies are lacking in the literature. The purpose of this paper is to provide an overview of the surgical skills necessary to successfully perform forelimb transplantation in canines as a means to prepare for clinical application. A total of 18 transplantation operations on canines were performed. The recipient limb was shortened at the one-third proximal forearm level. The operation was performed in the following order: bones (two reconstructive plates), muscles and tendons (separately sutured), nerves (median, ulnar, and radial nerve), arteries (two), and veins (two). The total mean time of transplantation was 5 hours ± 30 minutes. All of the animals that received transplantation were treated with FK-506 (tacrolimus, 2 mg/kg) for 7 days after surgery. Most allografts survived with perfect viability without vascular problems during the early postoperative period. The canine forelimb allotransplantation model is well qualified to be a suitable training model for standard transplantation and future research work. PMID:27597952

  9. Seroprevalence of Canine Distemper Virus in Cats

    OpenAIRE

    Ikeda, Yasuhiro; Nakamura, Kazuya; Miyazawa, Takayuki; Chen, Ming-Chu; Kuo, Tzong-Fu; Lin, James A; Mikami, Takeshi; Kai, Chieko; TAKAHASHI, Eiji

    2001-01-01

    A seroepidemiological survey of canine distemper virus (CDV) infection in Asian felids revealed that the prevalence of antibodies varied depending on region and, in some cases, exposure to dogs. The serologic pattern in cats with antibodies indicated that they had likely been exposed to field strains rather than typical CDV vaccine strains.

  10. Canine Distemper Outbreak in Rhesus Monkeys, China

    OpenAIRE

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang; Hu, Rongliang

    2011-01-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People’s Republic of China. Approximately 10,000 animals were infected (25%–60% disease incidence); 5%–30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain.

  11. Experimental Forelimb Allotransplantation in Canine Model.

    Science.gov (United States)

    Hong, Sa-Hyeok; Eun, Seok-Chan

    2016-01-01

    As reconstructive transplantation is gaining popularity as a viable alternative for upper limb amputees, it is becoming increasingly important for plastic surgeons to renew surgical skills and knowledge of this area. Forelimb allotransplantation research has been performed previously in rodent and swine models. However, preclinical canine forelimb allotransplantation studies are lacking in the literature. The purpose of this paper is to provide an overview of the surgical skills necessary to successfully perform forelimb transplantation in canines as a means to prepare for clinical application. A total of 18 transplantation operations on canines were performed. The recipient limb was shortened at the one-third proximal forearm level. The operation was performed in the following order: bones (two reconstructive plates), muscles and tendons (separately sutured), nerves (median, ulnar, and radial nerve), arteries (two), and veins (two). The total mean time of transplantation was 5 hours ± 30 minutes. All of the animals that received transplantation were treated with FK-506 (tacrolimus, 2 mg/kg) for 7 days after surgery. Most allografts survived with perfect viability without vascular problems during the early postoperative period. The canine forelimb allotransplantation model is well qualified to be a suitable training model for standard transplantation and future research work. PMID:27597952

  12. Overexpression of vimentin in canine prostatic carcinoma

    DEFF Research Database (Denmark)

    Rodrigues, M M P; Rema, A; Gärtner, F;

    2011-01-01

    is associated with the invasive phenotype of human prostate cancer cells. The aim of the present study was to characterize immunohistochemically the expression of vimentin by canine prostatic carcinomas. Primary carcinomas and metastatic tumour foci both showed vimentin expression. This finding suggests...

  13. Canine specific ELISA for coagulation factor VII

    DEFF Research Database (Denmark)

    Knudsen, Tom; Kjelgaard-Hansen, Mads; Tranholm, Mikael;

    2011-01-01

    available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable...

  14. Canine notoedric mange: a case report.

    Science.gov (United States)

    Leone, Federico

    2007-04-01

    Notoedric mange is a cutaneous ectoparasitic disease of cats caused by Notoedres cati, a mite belonging to the Sarcoptidae family. The disease occurs in felids, occasionally in other mammals and in humans. The canine form, even if cited by some authors, has never been documented. This report describes for the first time a case of notoedric mange in a dog.

  15. Canine retraction with J hook headgear.

    Science.gov (United States)

    Ayala Perez, C; de Alba, J A; Caputo, A A; Chaconas, S J

    1980-11-01

    Several methods have been described for accomplishing distal movement of canines without losing posterior anchorage. An accepted method in canine retraction is the use of headgear with J hooks. Since it incorporates extraoral anchorage, it is most effective in maximum-anchorage cases. It was the purpose of this study to analyze the distribution of force transmitted to the alveolus and surrounding structures by means of photoelastic visualization, utilizing J hook headgear for maxillary canine retraction. A three-dimensional model representing a human skull was used. This model was constructed with different birefringent materials to simulate bone, teeth, and periodontal membranes. Three different vectors of force were applied representing high-, medium-, and low-pull headgear, which were placed at angles of 40, 20, and 0 degrees to the occlusal plane. The photoelastic analysis was made by means of a circular-transmission polariscope arrangement, and the photoelastic data were recorded photographically. The stress areas created by the three different vectors of force were associated with various degrees of canine tipping. This effect was greater with the low-pull force component than with the medium-pull traction. The high-pull headgear produced the least tipping tendency, being closer to a bodily movemment effect. Further, stresses were transmitted to deeper structures of the simulated facial bones; these regions were the frontozygomatic, zygomaticomaxillary, and zygomaticotemporal sutures.

  16. Oral features and dental health in Hurler Syndrome following hematopoietic stem cell transplantation.

    LENUS (Irish Health Repository)

    McGovern, Eleanor

    2012-02-01

    BACKGROUND: Hurler Syndrome is associated with a deficiency of a specific lysosomal enzyme involved in the degradation of glycosaminoglycans. Hematopoietic stem cell transplantation (HSCT) in early infancy is undertaken to help prevent the accumulation of glycosaminoglycans and improve organ function. AIM: To investigate the oral features and dental health of patients with Hurler Syndrome who have undergone successful HSCT. MATERIALS AND METHODS: Twenty-five patients (median age 8.6 years) post-HSCT (mean age 9.4 months) underwent oral assessment (mean of 7.5 years post-HSCT). RESULTS: Dental development was delayed. Numerous occlusal anomalies were noted including: open-bite, class III skeletal base, dental spacing, primary molar infra-occlusion and ectopic tooth eruption. Dental anomalies included hypodontia, microdontia, enamel defects, thin tapering canine crowns, pointed molar cusps, bulbous molar crowns and molar taurodontism. Tooth roots were usually short\\/blunted\\/spindle-like in permanent molars. The prevalence of dental caries was low in the permanent dentition (mean DMFT 0.7) but high in the primary dentition (mean dmft 2.4). Oral hygiene instruction with plaque and or calculus removal was indicated in 71% of those that were dentate. CONCLUSION: Patients with Hurler Syndrome post-HSCT are likely to have delayed dental development, a malocclusion, and dental anomalies, particularly hypodontia and microdontia.

  17. 18F-FDG Positron Emission Tomography – An Innovative Technique for the Diagnosis of a Canine Lameness

    OpenAIRE

    Mann, Kelly; Hart, Juliette; Duerr, Felix

    2016-01-01

    Introduction Positron emission tomography (PET) imaging with fluorine-18-fluorodeoxyglucose (18F-FDG) is widely known for its use in the diagnosis and tracking of primary and metastatic tumors via uptake and retention of the radiopharmaceutical by hypermetabolic cells. 18F-FDG is also used to study the normal physiology of glucose uptake, metabolism, and muscle activity during and after exercise. Background A pilot study adding PET imaging to the diagnostic evaluation of canine patients under...

  18. Canine visceral leishmaniasis in Sicily.

    Science.gov (United States)

    Orndorff, G R; Cooper, B A; Smith, W; Ryan, J R

    2000-01-01

    The Sicilian province of Catania is an active foci for human visceral leishmaniasis (VL) in the Mediterranean area. Approximately 10 to 15 cases of VL are diagnosed via hospital admissions each year in this community. Recently, an increase in VL case reporting by Sicilian physicians was noted, with 38 and 37 VL cases in 1996 and 1997, respectively. Before 1995, there were no reported VL cases among U.S. military personnel or their family members living in Sicily. However, since 1996, there have been four cases referred to Walter Reed Army Medical Center for diagnosis and treatment, all involving the children of personnel assigned to Naval Air Station Sigonella. Exposure histories for all infected individuals excluded exposure to Leishmania parasites outside of Sicily. All patients lived in areas where vectoring sandflies are present. All had dogs as family pets. To evaluate the level of infection among dogs owned by Navy personnel and their families, U.S. Navy Environmental and Preventive Medicine Unit 7, in a collaborative study with the U.S. Army Veterinary Clinic, Naval Air Station Sigonella, and the Walter Reed Army Institute of Research, performed clinical evaluation and serological testing of 50 dogs residing with U.S. personnel assigned to Naval Air Station Sigonella. The data indicate a high exposure rate to Leishmania (60% of the animals tested had elevated immunoglobulin M antibody levels) in the study population, suggesting that they were infected with Leishmania infantum. Distribution of seropositive dogs by sex was equal. Most of the dogs studied appeared to be in good health. However, inapparent infection of dogs, seen by Italian veterinarians, has been observed throughout all areas of Catania. Sandflies responsible for vectoring L. infantum were trapped in the same locations as the dogs sampled in this study. The level of subclinical infection was 75% among seropositive dogs. The overall level of canine infection observed was higher than expected

  19. Canine neoplasia and exposure to uranium mill tailings in Mesa County, Colorado

    International Nuclear Information System (INIS)

    A canine cancer registry was established for Mesa County, Colorado in order to collect material for a case control analysis of exposure to uranium tailings. Between 1979 and 1981, 212 cases of canine cancer were confirmed histologically. Based on the address provided at the time of diagnosis, 33 dogs (15.6%) lived in a house with some exposure to uranium tailings. A control group, comprised of dogs with a histologic diagnosis other than cancer, was stratified according to hospital and matched with cases on a 1:1 basis. No significant differences were noted with respect to exposure to uranium tailings for total cancers or cancers of specific sites including lymph node, breast, liver, testicle and bone. The overall estimated relative risk was 0.70 (95% CI 0.04 to 1.16). Canine population estimates were derived for Mesa County in order to develop crude incidence rates for the major types and sites of cancer. Crude rates were compared with those published previously for Alameda County, California and Tulsa County, Oklahoma. Mesa County rates for total cancer incidence, connective tissue tumors and non melanoma skin cancer were higher than those reported for Alameda County. When compared with Tulsa County, Mesa County rates for total cancer, breast cancer, melanoma and mastocytoma were lower than expected while rates for osteosarcoma, hemangiosarcoma and fibrosarcoma significantly exceeded expected values

  20. Vitamin D Receptor, Retinoid X Receptor, Ki-67, Survivin, and Ezrin Expression in Canine Osteosarcoma

    Directory of Open Access Journals (Sweden)

    John Davies

    2012-01-01

    Full Text Available Canine osteosarcoma (OS is an aggressive malignant bone tumor. Prognosis is primarily determined by clinical parameters. Vitamin D has been postulated as a novel therapeutic option for many malignancies. Upon activation, vitamin D receptors (VDRs combine with retinoid receptor (RXR forming a heterodimer initiating a cascade of events. Vitamin D's antineoplastic activity and its mechanism of action in OS remain to be clearly established. Expression of VDR, RXR, Ki-67, survivin, and ezrin was studied in 33 archived, canine OS specimens. VDR, RXR, survivin, and ezrin were expressed in the majority of cases. There was no statistically significant difference in VDR expression in relationship with tumor grade, type, or locations or animal breed, age, and/or sex. No significant association (p=0.316 between tumor grade and Ki-67 expression was found; in particular, no difference in Ki-67 expression between grades 2 and 3 OSs was found, while a negative correlation was noted between Ki-67 and VDR expression (ρ=−0.466, a positive correlation between survivin and RXR expression was found (p=0.374. A significant relationship exists between VDR and RXR expression in OSs and proliferative/apoptosis markers. These results establish a foundation for elucidating mechanisms by which vitamin D induces antineoplastic activity in OS.

  1. Prostaglandin E2 increases hematopoietic stem cell survival and accelerates hematopoietic recovery after radiation injury

    OpenAIRE

    Porter, Rebecca L.; Georger, Mary; Bromberg, Olga; McGrath, Kathleen E.; Frisch, Benjamin J.; Becker, Michael W.; Calvi, Laura M.

    2013-01-01

    Hematopoietic stem and progenitor cells (HSPCs), which continuously maintain all mature blood cells, are regulated within the marrow microenvironment. We previously reported that pharmacologic treatment of naïve mice with prostaglandin E2 (PGE2) expands HSPCs. However, the cellular mechanisms mediating this expansion remain unknown. Here we demonstrate that PGE2 treatment in naïve mice inhibits apoptosis of HSPCs without changing their proliferation rate. In a murine model of sub-lethal total...

  2. Experimental Limitations Using Reprogrammed Cells for Hematopoietic Differentiation

    Directory of Open Access Journals (Sweden)

    Katharina Seiler

    2011-01-01

    Full Text Available We review here our experiences with the in vitro reprogramming of somatic cells to induced pluripotent stem cells (iPSC and subsequent in vitro development of hematopoietic cells from these iPSC and from embryonic stem cells (ESC. While, in principle, the in vitro reprogramming and subsequent differentiation can generate hematopoietic cell from any somatic cells, it is evident that many of the steps in this process need to be significantly improved before it can be applied to human cells and used in clinical settings of hematopoietic stem cell (HSC transplantations.

  3. Effects of canine serum collected from dogs at different estrous cycle stages on in vitro nuclear maturation of canine oocytes.

    Science.gov (United States)

    Oh, Hyun Ju; Fibrianto, Yuda Heru; Kim, Min Kyu; Jang, Goo; Hossein, M Shamim; Kim, Hye Jin; Kang, Sung Keun; Lee, Byeong Chun; Hwang, Woo Suk

    2005-08-01

    Canine oocytes are ovulated at prophase of the first meiotic division and undergo maturation in the distal part of the oviduct for at least 48-72 h. Because of these differences from other domestic mammals, the efficiency of in vitro maturation (IVM) of canine oocyte is very low. The present study was conducted to evaluate the effects of canine serum on IVM of canine oocytes recovered from ovaries in various reproductive states (follicular, luteal or anestrous stages). Oocytes were recovered by mincing ovaries from bitches presented for ovariohysterectomy at various stages of the estrous cycle. Heat-inactivated canine serum was prepared with blood taken from dogs at the anestrous, estrous or diestrous stage of the estrous cycle as determined by progesterone concentration and vaginal cytology. Oocytes were cultured for 72 h in tissue culture medium (TCM)-199 supplemented with 10% canine anestrous, estrous or diestrous serum or fetal bovine serum (FBS) (experiment 1), or supplemented with 0 (control), 5%, 10% or 20% canine estrous serum (experiment 2). In experiment 1, IVM of oocytes collected at the follicular stage of the estrous cycle to metaphase II (MII) stage was higher (p < 0.05) with canine estrous serum (14.2%) than with canine anestrous (5.2%) or diestrous serum (6.3%), FBS (2.2%) or in the control (2.2%). In experiment 2, oocytes collected at the follicular stage of the estrous cycle cultured in TCM-199 with 10% canine estrous serum showed a higher maturation rate to MII stage (13.5%, p < 0.05) compared with those cultured with 5% (1.3% MII) or 20% canine estrous serum (5.1% MII) or the control (2.7% MII). In conclusion, our results demonstrate that supplementing culture medium with 10% canine estrous serum improves IVM of canine follicular stage oocytes. PMID:16261767

  4. Tritium contamination of hematopoietic stem cells alters long-term hematopoietic reconstitution

    International Nuclear Information System (INIS)

    Purpose: In vivo effects of tritium contamination are poorly documented. Here, we study the effects of tritiated Thymidine ([3H] Thymidine) or tritiated water (HTO) contamination on the biological properties of hematopoietic stem cells (HSC). Materials and methods: Mouse HSC were contaminated with concentrations of [3H] Thymidine ranging from 0.37-37.03 kBq/ml or of HTO ranging from 5-50 kBq/ml. The biological properties of contaminated HSC were studied in vitro after HTO contamination and in vitro and in vivo after [3H] Thymidine contamination. Results: Proliferation, viability and double-strand breaks were dependent on [3H] Thymidine or HTO concentrations used for contamination but in vitro myeloid differentiation of HSC was not affected by [3H] Thymidine contamination. [3H] Thymidine contaminated HSC showed a compromised long-term capacity of hematopoietic reconstitution and competition experiments showed an up to two-fold decreased capacity of contaminated HSC to reconstitute hematopoiesis. These defects were not due to impaired homing in bone marrow but to an initial decreased proliferation rate of HSC. Conclusion: These results indicate that contaminations of HSC with doses of tritium that do not result in cell death, induce short-term effects on proliferation and cell cycle and long-term effects on hematopoietic reconstitution capacity of contaminated HSC. (authors)

  5. Radiation/hyperthermia in canine hemangiopericytomas: A large animal model for therapeutic response

    International Nuclear Information System (INIS)

    X-irradiation followed by microwave induced hyperthermia resulted in a 91% objective response rate in 11 dogs with naturally occurring hemangiopericytomas. The authors used a novel statistical procedure to quantitatively evaluate the clinical behavior of locally invasive, non-metastatic tumors undergoing therapy for control of local disease. Utilizing a small sample size, the procedure demonstrated distribution of the data and classical parametric and non-parametric statistical methods, including setting confidence limits on the population mean and placing tolerance limits on a population percentage. Similarities of canine and human hemangiopericytomas were observed. Application of the statistical methods to human and animal trials were apparent

  6. Claudin-1, -3, -4 and -7 gene expression analyses in canine prostate carcinoma and mammary tissue derived cell lines.

    Science.gov (United States)

    Hammer, S C; Nagel, S; Junginger, J; Hewicker-Trautwein, M; Wagner, S; Heisterkamp, A; Ngezahayo, A; Nolte, I; Murua Escobar, H

    2016-01-01

    Claudins (CLDNs) are transmembrane proteins localised in the cell membrane of epithelial cells composing a structural and functional component of the tight junction protein complexes. In canine tumors deregulations of the CLDN expression patterns were described immunohistochemically. Targeting of claudin proteins has further been evaluated to establish novel therapeutic approaches by directed claudin binding. Precondition for the development of claudin targeting approaches in canine cells is the possibility to characterise claudin expression specifically and the availability of claudin positive cell lines. Herein PCR/qPCR assays were established allowing a rapid qualitative and quantitative characterisation of CLDN-1, -3, -4 and -7 gene expression in canine cell lines and tissues. Further commercially available antibodies were used to verify CLDN gene expression on protein level by Western blots. The developed assays were used to analyse six canine cell lines derived from mammary and prostate tissue for their CLDN-1, -3, -4 and -7 expressions. The canine cell line DT08/40 (prostate transitional cell carcinoma) was used for the establishment of specific CLDNs -1, -3, -4 and -7PCR/qPCR. The designed assays were verified by amplicon cloning and sequencing. Gene expressions were verified on protein level by Western blot. Additionally further cell lines were analysed for their CLDN-1, -3, -4 and -7 expression on mRNA and protein level (mammary derived cell lines: MTH53A (non-neoplastic), ZMTH3 (adenoma), MTH52C (carcinoma); prostate derived cell lines: DT08/46 and CT1258 (both adenocarcinoma).The screened cell lines showed expression for the CLDNs as follows: DT08/46 and DT08/40: CLDN-1, -3, -4 and -7 positive; CT1258: CLDN-1, -3, -4 and -7 negative; ZMTH3 and MTH52C: CLDN-1 and -7 positive, CLDN-3 and -4 negative; MTH53A: CLDN-1, -3 and -4 negative, CLDN-7 positive. Western blot analyses reflect the detected CLDN-1, -3, -4 and -7 expressions in the analysed cell

  7. Preimmunization of donor lymphocytes enhances antitumor immunity of autologous hematopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    Lymphopenia-induced homeostatic proliferation (HP) of T cells following autologous hematopoietic stem cell transplantation (HSCT) skews the T-cell repertoire by engaging tumor-associated antigens (TAAs), leading to an induction of antitumor immunity. Here, as the tumor-reactive lymphocytes preferentially proliferate during the condition of HP, we examined whether the priming of a donor lymphocytes to TAAs could enhance HP-induced antitumor immunity in autologous HSCT recipients. First, to examine whether the tumor-bearing condition of donor influences the antitumor effect of HSCT, the lymphocytes isolated from CT26 tumor-bearing mice were infused into lethally irradiated mice. The growth of tumors was substantially suppressed in the mice that received HSCT from a tumor-bearing donor compared with a naïve donor, suggesting that a fraction of donor lymphocytes from tumor-bearing mice are primed in response to TAAs and remain responsive upon transplantation. We previously reported that type I interferon (IFN) maturates the dendritic cells and promotes the priming of T cells. We then investigated whether the further priming of donor cells by IFN-α can strengthen the antitumor effect of HSCT. The intratumoral IFN-α gene transfer significantly increased the number of IFN-γ-positive lymphocytes in response to CT26 cells but not the syngeneic lymphocytes in donor mice. The infusion of primed donor lymphocytes markedly suppressed the tumor growth in recipient mice, and cured 64% of the treated mice. Autologous HSCT with the infusion of primed donor lymphocytes is a promising strategy to induce an effective antitumor immunity for solid cancers

  8. Combined orthodontic-surgical management of a transmigrated mandibular canine.

    Science.gov (United States)

    Cavuoti, Serena; Matarese, Giovanni; Isola, Gaetano; Abdolreza, Jamilian; Femiano, Felice; Perillo, Letizia

    2016-07-01

    The presence of an impacted mandibular canine is one of the most difficult challenges that an orthodontist will meet. Orthodontic treatment is planned on an individual basis after thoroughly considering the patient's overall facial and dentoskeletal characteristics; the duration, risks, and costs of treatment; patient preferences; and the orthodontist's experience. This article reports an orthodontic treatment of a boy, age 12.9 years, with an impacted mandibular canine in the permanent dentition that was successfully managed. Radiographic analysis indicated a transmigration of the mandibular right canine. The orthodontic treatment plan included extraction of the deciduous right canine followed by surgical exposure and ligation of the permanent canine. Eruption was properly guided, and the correct position of the tooth was achieved. This challenging treatment approach is described in detail, including the mechanics used to align the impacted canine. PMID:26502299

  9. The Neuropsychiatry of Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Mitchell R. Levy

    2006-06-01

    Full Text Available BACKGROUND AND OBJECTIVES: Regimens incorporating hematopoietic stem cell transplantation (HSCT have become widely utilized in disease treatments, particularly for cancer. These complex treatment programs also expose patients to central nervous system (CNS toxicities from chemotherapy, irradiation, infection, metabolic effects and immunosuppression. METHODS: Relevant recent medical literature from Medline and bibliographies in pertinent publications are reviewed with a focus on those cases and studies pertaining to neuropsychiatric effects of HSCT. RESULTS: High rates of neuropsychiatric sequelae occur on a continuum from acute to chronic. Adverse outcomes include focal CNS deficits and severe global manifestations such as seizures, encephalopathy and delirium. More graduated effects on cognition, energy and mood are frequently seen, impacting patient function. CONCLUSIONS: Additional research on neuropsychiatric outcomes and treatment interventions is needed in the HSCT setting. Risks for neuropsychiatric deficits should be part of an ongoing informed consent discussion among treating physicians, patients and families.

  10. Engineering Hematopoietic Stem Cells: Lessons from Development.

    Science.gov (United States)

    Rowe, R Grant; Mandelbaum, Joseph; Zon, Leonard I; Daley, George Q

    2016-06-01

    Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain elusive due to insufficient long-term self-renewal and inadequate differentiated progeny functionality. A cross-species approach involving zebrafish and mammalian systems offers complementary methodologies to improve understanding of native HSCs. Here, we discuss the role of conserved developmental timing processes in vertebrate hematopoiesis, highlighting how identification and manipulation of stage-specific factors that specify HSC developmental state must be harnessed to engineer HSCs for therapy. PMID:27257760

  11. 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.

  12. Canine oral biofilms: Cultural, molecular, and in vitro studies.

    OpenAIRE

    Elliott, D. R.

    2006-01-01

    The canine oral microbiota is poorly understood compared to that of humans. The aim of this work was to improve understanding of the canine oral microbiota. This was achieved by surveying the canine oral microbiota, determining coaggregation interactions between its members, and developing a laboratory microcosm. Bacteria were isolated from the dental plaque and saliva of dogs, and isolates were identified by comparative 16S rRNA gene sequencing. From 339 isolates, 84 phylotypes belonging to ...

  13. Portrait of a Canine Probiotic – from Gut to Gut

    OpenAIRE

    O'Mahony, D.; Murphy, K. Barry; MacSharry, J.; Boileau, T.; Sunvold, G.; Reinhart, G.; Kiely, B.; Shanahan, F; O'Mahony, L.

    2009-01-01

    Abstract The gastrointestinal environment is a complex interactive system involving the host, ingested dietary components, and numerous microbial species. We hypothesised that isolation and screening of Lactobacilli and Bifidobacteria adherent to healthy canine gastrointestinal tissue would yield strains with commensal activity in canines. The aims of this study were 1) to isolate a bank of commensal organisms from the canine gastrointestinal tract; 2) to screen these novel microbi...

  14. Validation of commercially available automated canine-specific immunoturbidimetric method for measuring canine C-reactive protein

    DEFF Research Database (Denmark)

    Hillström, Anna; Hagman, Ragnvi; Tvedten, Harold;

    2014-01-01

    with a human CRP assay previously validated for canine CRP determination. Samples from 40 healthy dogs were analyzed to establish a reference interval. RESULTS: Total imprecision was ..., there was good agreement between the validated human CRP assay and the new canine-specific assay. Healthy dogs had CRP concentrations that were less than the limit of quantification of the Gentian cCRP method (6.8 mg/L). CONCLUSIONS: The new canine-specific immunoturbidimetric CRP assay is a reliable and rapid......BACKGROUND: Measurement of C-reactive protein (CRP) is used for diagnosing and monitoring systemic inflammatory disease in canine patients. An automated human immunoturbidimetric assay has been validated for measuring canine CRP, but cross-reactivity with canine CRP is unpredictable. OBJECTIVE...

  15. Circulation and chemotaxis of fetal hematopoietic stem cells.

    OpenAIRE

    Christensen, Julie L.; Wright, Douglas E.; Wagers, Amy J.; Weissman, Irving L.

    2004-01-01

    The major site of hematopoiesis transitions from the fetal liver to the spleen and bone marrow late in fetal development. To date, experiments have not been performed to evaluate functionally the migration and seeding of hematopoietic stem cells (HSCs) during this period in ontogeny. It has been proposed that developmentally timed waves of HSCs enter the bloodstream only during distinct windows to seed the newly forming hematopoietic organs. Using competitive reconstitution assays to measure ...

  16. Breed predisposition to canine gastric carcinoma

    DEFF Research Database (Denmark)

    Seim-Wikse, Tonje; Jörundsson, Einar; Nødtvedt, Ane;

    2013-01-01

    Previous research has indicated a breed predisposition to gastric carcinoma in dogs. However, results to date are inconsistent since several studies have failed to prove such a predisposition. Better knowledge of breeds at risk could facilitate early detection of gastric carcinoma in dogs. The ai...... of the study was to retrospectively investigate the proportion and possible breed predisposition to canine gastric carcinoma using the Norwegian Canine Cancer Register for calculations of proportional morbidity ratios (PMRs) for the period 1998-2009.......Previous research has indicated a breed predisposition to gastric carcinoma in dogs. However, results to date are inconsistent since several studies have failed to prove such a predisposition. Better knowledge of breeds at risk could facilitate early detection of gastric carcinoma in dogs. The aim...

  17. Antigenic typing Polish isolates of canine parvovirus

    Energy Technology Data Exchange (ETDEWEB)

    Mizak, B. [National Veterinary Research Institute, Pulawy (Poland); Plucienniczak, A. [Polish Academy ofd Sciences. Microbiology and Virology Center, Lodz (Poland)

    1995-12-31

    Polish strains of canine parvovirus isolated between 1982 and 1993 were examined to determine the extent to which the virus has evolved antigenically and genetically over eleven years. Two CPV isolates obtained in Warsaw in 1982 and Pulawy in 1993, were examined using monoclonal antibody typing, restriction analysis and sequencing VP-2 protein gene. Five other isolates from Warsaw and Pulawy were tested with the panel of monoclonal antibodies specific to CPV-2, CPV-2a and common for canine parvovirus, feline panleukopenia virus and milk enteritis virus. Results of the studies demonstrated that all isolates tested represented CPV-2a antigenic type. Rapid antigenic strain replacement recorded by Parrish and Senda in the U.S.A and Japan was not confirmed in Poland. (author). 30 refs, 2 tabs.

  18. Coryneform bacteria associated with canine otitis externa

    DEFF Research Database (Denmark)

    Aalbæk, Bent; Bemis, David A.; Schjærff, Mette;

    2010-01-01

    This study aims to investigate the occurrence of coryneform bacteria in canine otitis externa. A combined case series and case-control study was carried out to improve the current knowledge on frequency and clinical significance of coryneform bacteria in samples from canine otitis externa. A total...... of 16 cases of otitis externa with involvement of coryneform bacteria were recorded at two referral veterinary hospitals in Denmark and the US, respectively. Coryneform bacteria were identified by partial 16S rRNA gene sequencing. Corynebacterium auriscanis was the most common coryneform species (10...... cases). Small colony variants of this species were also observed. Other coryneform isolates were identified as Corynebacterium amycolatum (3 cases), Corynebacterium freneyi (2 cases) and an Arcanobacterium-like species (1 case). The coryneform bacteria were in all cases isolated together with other...

  19. Aggressive Calcifying Epithelial Odontogenic Tumor of the Maxillary Sinus with Extraosseous Oral Mucosal Involvement: A Case Report

    OpenAIRE

    Vidya Rani; Mahaboob Kadar Masthan; Babu Aravindha; Sankari Leena

    2016-01-01

    Calcifying epithelial odontogenic tumors are benign odontogenic neoplasms whose occurrence in the maxillary sinus is rare. Maxillary tumors tend to be locally aggressive and may rapidly involve the surrounding vital structures. We report a case of a large calcifying epithelial odontogenic tumor of the maxilla, involving the maxillary sinus in a 48-year-old woman. The tumor was largely intraosseous. In the canine and first premolar regions, the loss of bone could be palpated but the oral mucos...

  20. Extrusion processing : effects on dry canine diets

    OpenAIRE

    Tran, Q.D.

    2008-01-01

    Keywords: Extrusion, Canine diet, Protein, Lysine, Starch gelatinization, Palatability, Drying. Extrusion cooking is a useful and economical tool for processing animal feed. This high temperature, short time processing technology causes chemical and physical changes that alter the nutritional and physical quality of the product. Effects of extrusion on the feed quality for other animals than pets have been well recognized. Our studies investigated to what extent extrusion and/or drying of a c...

  1. Cardiac troponin I levels in canine pyometra

    OpenAIRE

    Hagman Ragnvi; Lagerstedt Anne-Sofie; Fransson Boel A; Bergström Annika; Häggström Jens

    2007-01-01

    Abstract Background Myocardial injury may contribute to unexpected deaths due to pyometra. To detect myocardial damage, measurement of cardiac troponin I (cTnI) is currently the most sensitive and specific method. The aims of the present study were to evaluate presence of myocardial damage in canine pyometra by analysis of cTnI, to explore whether myocardial injury was associated with systemic inflammatory response syndrome (SIRS) and to evaluate whether other clinical or laboratory parameter...

  2. Microbiological and histopathological aspects of canine pyometra

    OpenAIRE

    Coggan, Jennifer Anne; Melville, Priscilla Anne; de Oliveira, Clair Motos; Faustino, Marcelo; Moreno, Andréa Micke; Benites, Nilson Roberti

    2008-01-01

    As pyometra is recognized as one of the main causes of disease and death in the bitch the purposes of this study were to evaluate microbiological and histopathological aspects of canine pyometra and to research the virulence factors of the E. coli isolates identifying possible risks to human health. The microbiological isolation from the intrauterine contents of 100 dogs with pyometra was carried out and the virulence factors in the E. coli strains were identified using PCR method. This study...

  3. Remote detection of explosives using trained canines

    International Nuclear Information System (INIS)

    Use of dogs is a search method which combines high probability of detection, speed of search, and low cost. It was concluded that the canine could be used for explosive screening of personnel, but that it was imperative that the dog be in a position remote from employees and employee traffic. A study was made of the design of booths and air flow for this purpose. Results of tests and conclusions are given and discussed

  4. Treatment of canine scabies with milbemycin oxime.

    Science.gov (United States)

    Miller, W H; de Jaham, C; Scott, D W; Cayatte, S M; Bagladi, M S; Buerger, R G

    1996-04-01

    The purpose of this study was to determine the efficacy of orally administered milbemycin oxime in the treatment of canine scabies. Forty dogs were treated. Mean drug dosage for all dogs was approximately 2 mg/kg body weight. Twenty-seven dogs received 3 doses separated by 7 d, and 13 dogs received 2 doses separated by 14 d. All dogs were clinically normal following treatment and no adverse reactions were detected.

  5. Induction of embryonic stem cells to hematopoietic cells in vitro

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In order to get hematopoietic cells from embryonic stem (ES) cells and to study development mechanisms of hematopoietic cells, the method of inducing embryonic stem cells to hematopoietic cells was explored by differenciating mouse ES cells and human embryonic cells in three stages. The differentiated cells were identified by flow cytometry, immunohistochemistry and Wright's staining. The results showed that embryoid bodies (EBs) could form when ES cells were cultured in the medium with 2-mercaptoethanol (2-ME). However, cytokines, such as stem cell factor (SCF), thrombopoietin (TPO), interleukin-3 (IL-3), interleukin-6 (IL-6), erythropoietin (EPO) and granular colony stimulating factor (G-CSF), were not helpful for forming EBs. SCF, TPO and embryonic cell conditional medium were useful for the differentiation of mouse EBs to hematopoietic progenitors. Eighty-six percent of these cells were CD34+ after 6-d culture. Hematopoietic progenitors differentiated to B lymphocytes when they were cocultured with primary bone marrow stroma cells in the DMEM medium with SCF and IL-6. 14 d later, most of the cells were CD34-CD38+. Wright's staining and immunohistochemistry showed that 80% of these cells were plasma-like morphologically and immunoglubolin positive. The study of hematopoietic cells from human embryonic cells showed that human embryonic cell differentiation was very similar to that of mouse ES cells. They could form EBs in the first stage and the CD34 positive cells account for about 48.5% in the second stage.

  6. Parathyroid hormone mediates hematopoietic cell expansion through interleukin-6.

    Directory of Open Access Journals (Sweden)

    Flavia Q Pirih

    Full Text Available Parathyroid hormone (PTH stimulates hematopoietic cells through mechanisms of action that remain elusive. Interleukin-6 (IL-6 is upregulated by PTH and stimulates hematopoiesis. The purpose of this investigation was to identify actions of PTH and IL-6 in hematopoietic cell expansion. Bone marrow cultures from C57B6 mice were treated with fms-like tyrosine kinase-3 ligand (Flt-3L, PTH, Flt-3L plus PTH, or vehicle control. Flt-3L alone increased adherent and non-adherent cells. PTH did not directly impact hematopoietic or osteoclastic cells but acted in concert with Flt-3L to further increase cell numbers. Flt-3L alone stimulated proliferation, while PTH combined with Flt-3L decreased apoptosis. Flt-3L increased blasts early in culture, and later increased CD45(+ and CD11b(+ cells. In parallel experiments, IL-6 acted additively with Flt-3L to increase cell numbers and IL-6-deficient bone marrow cultures (compared to wildtype controls but failed to amplify in response to Flt-3L and PTH, suggesting that IL-6 mediated the PTH effect. In vivo, PTH increased Lin(- Sca-1(+c-Kit(+ (LSK hematopoietic progenitor cells after PTH treatment in wildtype mice, but failed to increase LSKs in IL-6-deficient mice. In conclusion, PTH acts with Flt-3L to maintain hematopoietic cells by limiting apoptosis. IL-6 is a critical mediator of bone marrow cell expansion and is responsible for PTH actions in hematopoietic cell expansion.

  7. Microbial profile of canine persistent wound infections

    Directory of Open Access Journals (Sweden)

    A. Padhy

    2014-04-01

    Full Text Available Aim: To analyse the microbial profile of canine persistent wound infections. Materials and Methods: The total wound samples (n=172 taken from both traumatic (140 and post-surgical (32 persistent wounds in canines were processed for routine microbial isolation and identification during a period of 15 months. Results: Staphylococcus intermedius was found to be the predominant isolate from all types of wounds under study. It was followed by Staphylococcus aureus, Pseudomonas aeruginosa, E. coli, Pasteurella spp., Corynaebacterium spp. and Bacillus spp. From different traumatic wounds of dogs, S. intermedius (92/140=65.7% and from surgical wounds, P. aeruginosa (24/32=75% were found to be the predominant isolates recovered whereas the most commonly isolated bacterial genus in both traumatic and surgical wounds of dogs was Staphylococcus spp. Conclusion: Canine wounds are polymicrobial in nature. Hence proper microbial laboratory diagnosis and presence of multiple organisms in a wound are to be taken into consideration for effective treatment of persistent wound infections in dogs.

  8. Canine kobuviruses in diarrhoeic dogs in Italy.

    Science.gov (United States)

    Di Martino, Barbara; Di Felice, Elisabetta; Ceci, Chiara; Di Profio, Federica; Marsilio, Fulvio

    2013-09-27

    Canine kobuviruses (CaKVs) are newly recognized picornaviruses recently detected in dogs in the US. By molecular analysis of the whole genome, CaKV that appeared genetically closest to the murine kobuvirus (MuKV) and to the human Aichi virus (AiV), may be classified in the Kobuvirus genus as new genotype (CaKV type 1) within the species Aichivirus A. To date, there are no information on the epidemiology of these novel viruses in other continents. In this study, by screening a collection of 256 dog fecal samples either from diarrhoeic or asymptomatic animals, CaKV was identified in six specimens with an overall prevalence of 2.34% (6/256). All the positive dogs presented diarrhea and were found to be infected by CaKV alone or in mixed infections with canine coronavirus (CCoV) and/or canine parvovirus type 2 (CPV-2). By molecular analysis of the partial 3D gene, all the strains detected displayed a close relatedness with the CaKVs recently identified in the US. This study provides evidence that CaKVs circulate in diarrhoeic dogs in Italy and are not geographically restricted to the North American continent, where they were first signaled. PMID:23806200

  9. Cytodiagnostics of canine lymphomas - possibilities and limitations.

    Science.gov (United States)

    Sapierzyński, R; Kliczkowska-Klarowicz, K; Jankowska, U; Jagielski, D

    2016-01-01

    Malignant lymphomas are one of the most common malignant tumours occurring in dogs. The basic method of lymphoma diagnosis in human, as well as in canine oncology is histopathology supported by immunohistochemistry. It was suggested that in veterinary medicine excisional biopsy of lymph node and histopathology should be considered only where the cytologic diagnosis is equivocal or needs to be confirmed. There are at least three basic reasons for which cytological examination ought to be accepted as a sufficient and reliable diagnostic method for lymphoma in dogs. Firstly, most dog owners consider the fine-needle biopsy as an acceptable non-harmful method of sample collection. Secondly, an increasing number of studies recommend cytology as an accurate test for diagnosing and subtyping canine lymphoma. Finally, the vast majority of canine lymphoma subtypes belong to 4-5 categories characterized by a typical cytological picture. Immunocytochemical staining of cytological smears gives new diagnostic possibilities, such as detection of markers better characterizing given growth or a potential goal for target therapy in individual cases (for example inhibitors of platelet-derived growth factor). PMID:27487521

  10. Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Danilo Santana Alessio Franceschi

    2011-01-01

    Full Text Available Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.

  11. Regulation of hematopoiesis and the hematopoietic stem cell niche by Wnt signaling pathways

    Institute of Scientific and Technical Information of China (English)

    Michael J Nemeth; David M Bodine

    2007-01-01

    Hematopoietic stem cells (HSCs) are a rare population of cells that are responsible for life-long generation of blood cells of all lineages. In order to maintain their numbers, HSCs must establish a balance between the opposing cell fates of self-renewal (in which the ability to function as HSCs is retained) and initiation of hematopoietic differentiation. Multiple signaling pathways have been implicated in the regulation of HSC cell fate. One such set of pathways are those activated by the Wnt family of ligands. Wnt signaling pathways play a crucial role during embryogenesis and deregulation of these pathways has been implicated in the formation of solid tumors. Wnt signaling also plays a role in the regulation of stem cells from multiple tissues, such as embryonic, epidermal, and intestinal stem cells. However, the function of Wnt signaling in HSC biology is still controversial. In this review, we will discuss the basic characteristics of the adult HSC and its regulatory microenvironment, the "niche", focusing on the regulation of the HSC and its niche by the Wnt signaling pathways.

  12. Cytokine-Regulated GADD45G Induces Differentiation and Lineage Selection in Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Frederic B. Thalheimer

    2014-07-01

    Full Text Available The balance of self-renewal and differentiation in long-term repopulating hematopoietic stem cells (LT-HSC must be strictly controlled to maintain blood homeostasis and to prevent leukemogenesis. Hematopoietic cytokines can induce differentiation in LT-HSCs; however, the molecular mechanism orchestrating this delicate balance requires further elucidation. We identified the tumor suppressor GADD45G as an instructor of LT-HSC differentiation under the control of differentiation-promoting cytokine receptor signaling. GADD45G immediately induces and accelerates differentiation in LT-HSCs and overrides the self-renewal program by specifically activating MAP3K4-mediated MAPK p38. Conversely, the absence of GADD45G enhances the self-renewal potential of LT-HSCs. Videomicroscopy-based tracking of single LT-HSCs revealed that, once GADD45G is expressed, the development of LT-HSCs into lineage-committed progeny occurred within 36 hr and uncovered a selective lineage choice with a severe reduction in megakaryocytic-erythroid cells. Here, we report an unrecognized role of GADD45G as a central molecular linker of extrinsic cytokine differentiation and lineage choice control in hematopoiesis.

  13. An adenomatoid odontogenic tumor in disguise.

    Science.gov (United States)

    Dhirawani, Rajesh B; Pathak, Sanyog; Mallikaarjuna, K; Sharma, Ankit

    2016-01-01

    Adenomatoid odontogenic tumor (AOT) is a slowly growing benign tumor of the oral cavity. It accounts of 3-7% of all odontogenic tumors. It is seen to occur commonly in the anterior maxilla. The tumor is usually associated with an impacted tooth with maxillary canine being the most common tooth. AOT is seen in a younger group, especially below 20 years with a female preponderance. AOT occurs in two main variants: Central or intraosseous which is more common and second is peripheral which is rare. Radiologically, it represents as a radiolucent lesion with radiopaque foci usually an impacted or a supernumerary tooth. With a close clinical and radiographic resemblance to dentigerous cyst correct diagnosis and treatment is necessary. AOT being benign in nature requires a conservative management with enucleation. This is a case report of a 13-year-old girl with an AOT occurring in the anterior maxillary region. PMID:27461816

  14. Human Flt3L generates dendritic cells from canine peripheral blood precursors: implications for a dog glioma clinical trial.

    Directory of Open Access Journals (Sweden)

    Weidong Xiong

    Full Text Available BACKGROUND: Glioblastoma multiforme (GBM is the most common primary brain tumor in adults and carries a dismal prognosis. We have developed a conditional cytotoxic/immunotherapeutic approach using adenoviral vectors (Ads encoding the immunostimulatory cytokine, human soluble fms-like tyrosine kinase 3 ligand (hsFlt3L and the conditional cytotoxic molecule, i.e., Herpes Simplex Type 1- thymide kinase (TK. This therapy triggers an anti-tumor immune response that leads to tumor regression and anti-tumor immunological memory in intracranial rodent cancer models. We aim to test the efficacy of this immunotherapy in dogs bearing spontaneous GBM. In view of the controversy regarding the effect of human cytokines on dog immune cells, and considering that the efficacy of this treatment depends on hsFlt3L-stimulated dendritic cells (DCs, in the present work we tested the ability of Ad-encoded hsFlt3L to generate DCs from dog peripheral blood and compared its effects with canine IL-4 and GM-CSF. METHODOLOGY/PRINCIPAL FINDINGS: Our results demonstrate that hsFlT3L expressed form an Ad vector, generated DCs from peripheral blood cultures with very similar morphological and phenotypic characteristics to canine IL-4 and GM-CSF-cultured DCs. These include phagocytic activity and expression of CD11c, MHCII, CD80 and CD14. Maturation of DCs cultured under both conditions resulted in increased secretion of IL-6, TNF-alpha and IFN-gamma. Importantly, hsFlt3L-derived antigen presenting cells showed allostimulatory potential highlighting their ability to present antigen to T cells and elicit their proliferation. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that hsFlt3L induces the proliferation of canine DCs and support its use in upcoming clinical trials for canine GBM. Our data further support the translation of hsFlt3L to be used for dendritic cells' vaccination and gene therapeutic approaches from rodent models to canine patients and its future

  15. Tumor-altered dendritic cell function: implications for anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Kristian Michael Hargadon

    2013-07-01

    Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti-tumor

  16. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... parvovirus susceptible dogs (20 vaccinates and 5 controls) shall be used as test animals. Blood samples...

  17. Stroma and extracellular matrix proteins in canine tumours

    NARCIS (Netherlands)

    Mukaratirwa, Sydney

    2004-01-01

    In this thesis, studies on temporal and spatial changes in stromal cells and extracellular matrix (ECM) molecules in canine gastrointestinal (GIT) tumours and canine transmissible venereal (CTVT) tumours are described. The mechanisms involved in the phenotypic transformation of fibroblasts to myofib

  18. Canine evolution in sabretoothed carnivores: natural selection or sexual selection?

    Science.gov (United States)

    Randau, Marcela; Carbone, Chris; Turvey, Samuel T

    2013-01-01

    The remarkable elongated upper canines of extinct sabretoothed carnivorous mammals have been the subject of considerable speculation on their adaptive function, but the absence of living analogues prevents any direct inference about their evolution. We analysed scaling relationships of the upper canines of 20 sabretoothed feliform carnivores (Nimravidae, Barbourofelidae, Machairodontinae), representing both dirk-toothed and scimitar-toothed sabretooth ecomorphs, and 33 non-sabretoothed felids in relation to body size in order to characterize and identify the evolutionary processes driving their development, using the scaling relationships of carnassial teeth in both groups as a control. Carnassials display isometric allometry in both sabretooths and non-sabretooths, supporting their close relationship with meat-slicing, whereas the upper canines of both groups display positive allometry with body size. Whereas there is no statistical difference in allometry of upper canine height between dirk-toothed and scimitar-toothed sabretooth ecomorphs, the significantly stronger positive allometry of upper canine height shown by sabretooths as a whole compared to non-sabretooths reveals that different processes drove canine evolution in these groups. Although sabretoothed canines must still have been effective for prey capture and processing by hypercarnivorous predators, canine morphology in these extinct carnivores was likely to have been driven to a greater extent by sexual selection than in non-sabretooths. Scaling relationships therefore indicate the probable importance of sexual selection in the evolution of the hypertrophied sabretooth anterior dentition. PMID:23951334

  19. Canine evolution in sabretoothed carnivores: natural selection or sexual selection?

    Directory of Open Access Journals (Sweden)

    Marcela Randau

    Full Text Available The remarkable elongated upper canines of extinct sabretoothed carnivorous mammals have been the subject of considerable speculation on their adaptive function, but the absence of living analogues prevents any direct inference about their evolution. We analysed scaling relationships of the upper canines of 20 sabretoothed feliform carnivores (Nimravidae, Barbourofelidae, Machairodontinae, representing both dirk-toothed and scimitar-toothed sabretooth ecomorphs, and 33 non-sabretoothed felids in relation to body size in order to characterize and identify the evolutionary processes driving their development, using the scaling relationships of carnassial teeth in both groups as a control. Carnassials display isometric allometry in both sabretooths and non-sabretooths, supporting their close relationship with meat-slicing, whereas the upper canines of both groups display positive allometry with body size. Whereas there is no statistical difference in allometry of upper canine height between dirk-toothed and scimitar-toothed sabretooth ecomorphs, the significantly stronger positive allometry of upper canine height shown by sabretooths as a whole compared to non-sabretooths reveals that different processes drove canine evolution in these groups. Although sabretoothed canines must still have been effective for prey capture and processing by hypercarnivorous predators, canine morphology in these extinct carnivores was likely to have been driven to a greater extent by sexual selection than in non-sabretooths. Scaling relationships therefore indicate the probable importance of sexual selection in the evolution of the hypertrophied sabretooth anterior dentition.

  20. Application of biodynamic imaging for personalized chemotherapy in canine lymphoma

    Science.gov (United States)

    Custead, Michelle R.

    Biodynamic imaging (BDI) is a novel phenotypic cancer profiling technology which characterizes changes in cellular and subcellular motion in living tumor tissue samples following in vitro or ex vivo treatment with chemotherapeutics. The ability of BDI to predict clinical response to single-agent doxorubicin chemotherapy was tested in ten dogs with naturally-occurring non-Hodgkin's lymphomas (NHL). Pre-treatment tumor biopsy samples were obtained from all dogs and treated with doxorubicin (10 muM) ex vivo. BDI captured cellular and subcellular motility measures on all biopsy samples at baseline and at regular intervals for 9 hours following drug application. All dogs subsequently received treatment with a standard single-agent doxorubicin protocol. Objective response (OR) to doxorubicin and progression-free survival time (PFST) following chemotherapy were recorded for all dogs. The dynamic biomarkers measured by BDI were entered into a multivariate logistic model to determine the extent to which BDI predicted OR and PFST following doxorubicin therapy. The model showed that the sensitivity, specificity, and accuracy of BDI for predicting treatment outcome were 95%, 91%, and 93%, respectively. To account for possible over-fitting of data to the predictive model, cross-validation with a one-left-out analysis was performed, and the adjusted sensitivity, specificity, and accuracy following this analysis were 93%, 87%, and 91%, respectively. These findings suggest that BDI can predict, with high accuracy, treatment outcome following single-agent doxorubicin chemotherapy in a relevant spontaneous canine cancer model, and is a promising novel technology for advancing personalized cancer medicine.

  1. The canine papillomavirus and gamma HPV E7 proteins use an alternative domain to bind and destabilize the retinoblastoma protein.

    Directory of Open Access Journals (Sweden)

    Jingang Wang

    Full Text Available The high-risk HPV E6 and E7 proteins cooperate to immortalize primary human cervical cells and the E7 protein can independently transform fibroblasts in vitro, primarily due to its ability to associate with and degrade the retinoblastoma tumor suppressor protein, pRb. The binding of E7 to pRb is mediated by a conserved Leu-X-Cys-X-Glu (LXCXE motif in the conserved region 2 (CR2 of E7 and this domain is both necessary and sufficient for E7/pRb association. In the current study, we report that the E7 protein of the malignancy-associated canine papillomavirus type 2 encodes an E7 protein that has serine substituted for cysteine in the LXCXE motif. In HPV, this substitution in E7 abrogates pRb binding and degradation. However, despite variation at this critical site, the canine papillomavirus E7 protein still bound and degraded pRb. Even complete deletion of the LXSXE domain of canine E7 failed to interfere with binding to pRb in vitro and in vivo. Rather, the dominant binding site for pRb mapped to the C-terminal domain of canine E7. Finally, while the CR1 and CR2 domains of HPV E7 are sufficient for degradation of pRb, the C-terminal region of canine E7 was also required for pRb degradation. Screening of HPV genome sequences revealed that the LXSXE motif of the canine E7 protein was also present in the gamma HPVs and we demonstrate that the gamma HPV-4 E7 protein also binds pRb in a similar way. It appears, therefore, that the type 2 canine PV and gamma-type HPVs not only share similar properties with respect to tissue specificity and association with immunosuppression, but also the mechanism by which their E7 proteins interact with pRb.

  2. Hematopoietic stem cell characterization and isolation.

    Science.gov (United States)

    Rossi, Lara; Challen, Grant A; Sirin, Olga; Lin, Karen Kuan-Yin; Goodell, Margaret A

    2011-01-01

    Hematopoietic stem cells (HSCs) are defined by the capabilities of multi-lineage differentiation and long-term self-renewal. Both these characteristics contribute to maintain the homeostasis of the system and allow the restoration of hematopoiesis after insults, such as infections or therapeutic ablation. Reconstitution after lethal irradiation strictly depends on a third, fundamental property of HSCs: the capability to migrate under the influence of specific chemokines. Directed by a chemotactic compass, after transplant HSCs find their way to the bone marrow, where they eventually home and engraft. HSCs represent a rare population that primarily resides in the bone marrow with an estimated frequency of 0.01% of total nucleated cells. Separating HSCs from differentiated cells that reside in the bone marrow has been the focus of intense investigation for years. In this chapter, we will describe in detail the strategy routinely used by our laboratory to purify murine HSCs, by exploiting their antigenic phenotype (KSL), combined with the physiological capability to efficiently efflux the vital dye Hoechst 33342, generating the so-called Side Population, or SP.

  3. Apicotomy: surgical management of maxillary dilacerated or ankylosed canines.

    Science.gov (United States)

    Araújo, Eustáquio A; Araújo, Cristiana V; Tanaka, Orlando M

    2013-12-01

    This clinical article reports a technique, apicotomy, for managing dilacerated or ankylosed canines. The records of 3 patients successfully treated with apicotomy are presented. Orthodontists observe clinically significant incidences of impacted maxillary canines in their daily practices. Several procedures have been described to bring an ankylosed, impacted tooth into occlusion. Luxation is the most widely used solution, but there are risks involved with that approach, and the success rate is low. Surgical repositioning has also been used, but morbidity is high, and the aggressiveness of the procedure might also contraindicate it. Ankylosis might be related to the anatomic position of the canine's root apex and its adjacent anatomic structures. Apicotomy is a guided fracture of a canine root apex, followed by its orthodontic traction. It is a conservative surgical alternative for treating impacted canines with dilacerations or apical root ankylosis. PMID:24286914

  4. Morphology and immunoreactivity of canine and feline extramedullary plasmacytomas.

    Science.gov (United States)

    Mikiewicz, M; Otrocka-Domagała, I; Paździor-Czapula, K; Gesek, M

    2016-01-01

    The aim of the study was the evaluation of morphology and immunophenotype of canine (19 cases) and feline (7 cases) extramedullary plasmacytomas. Tumours, located in skin, oral cavity and spleen were surgically excised, fixed and processed for histopathology and immunohistochemistry (CD79α, CD18, proliferating cell nuclear antigen, metallothionein). Histologically, tumours were classified into mature, cleaved, asynchronous, polymorphous blastic, hyalin, or monomorphous blastic type. All evaluated tumours showed cytoplasmic expression of CD79α antigen. The expression of CD18 was observed in canine cutaneous and splenic tumours. In canine tumours expression of metallothionein was low to moderate, while in feline plasmacytomas - absent or low. In canine tumours, the mitotic index and proliferating cell nuclear antigen index were positively correlated with the expression of metallothionein. In feline tumours no correlation between mitotic index, proliferating cell nuclear antigen and metallothionein was found. This is the first study describing expression of metallothionein in canine and feline extramedullary plasmacytoma. PMID:27487508

  5. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    Directory of Open Access Journals (Sweden)

    Armando Vilchis-Ordoñez

    2015-01-01

    Full Text Available B-cell acute lymphoblastic leukemia (B-ALL is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNFα, IL-1β, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13+CD33+ population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow.

  6. [Benign odontogenic tumor in the lower jaw: A case report].

    Science.gov (United States)

    Bassetti, Renzo; Tomasetti, Patrick; Crameri, Manuel; Kuttenberger, Johannes

    2016-01-01

    Odontomas are classified within the group of odontogenic epithelial tumors with odontogenic ectomesenchyme with or without hard tissue formation. Together with ameloblastomas and keratocystic odontogenic tumors they are counted among the most common odontogenic tumors. Their growth is self-limiting and mostly, they are discovered accidentally as part of a x-ray examination. A common finding is that odontomas are associated with an unerupted permanent tooth. The aim of the present case report is to present the step-by-step procedure of a surgical odontoma removal in the lingual premolar/canine area of the lower jaw.

  7. In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells

    OpenAIRE

    Amabile, Giovanni; Welner, Robert S.; Nombela-Arrieta, Cesar; D'Alise, Anna Morena; Di Ruscio, Annalisa; Ebralidze, Alexander K.; Kraytsberg, Yevgenya; Ye, Min; Kocher, Olivier; Neuberg, Donna S.; Khrapko, Konstantin; Silberstein, Leslie E.; Tenen, Daniel G

    2013-01-01

    Human hematopoietic cells develop within human iPSC-derived teratomas in immunodeficient mice.Co-transplantation of OP9 stromal cells along with human iPSCs increases hematopoietic specification within teratomas.

  8. Hematopoietic organs of Manduca sexta and hemocyte lineages.

    Science.gov (United States)

    Nardi, James B; Pilas, Barbara; Ujhelyi, Elizabeth; Garsha, Karl; Kanost, Michael R

    2003-10-01

    Cells of the moth immune system are derived from organs that loosely envelop the four wing imaginal discs. The immune response in these insects is believed to depend on the activities of two main classes of hemocytes: plasmatocytes and granular cells. The fates of cells that arise from these hematopoietic organs have been followed by immunolabeling with plasmatocyte-specific and granular-cell-specific antibodies. Cells within each hematopoietic organ differ in their coherence and in their expression of two plasmatocyte-specific surface proteins, integrin and neuroglian. Within an organ there is no overlap in the expression of these two surface proteins; neuroglian is found on the surfaces of the coherent cells while integrin is expressed on cells that are losing coherence, rounding up, and dispersing. A granular-cell-specific marker for the protein lacunin labels the basal lamina that delimits each organ but only a small number of granular cells that lie on or near the periphery of the hematopoietic organ. When organs are cultured in the absence of hemolymph, all cells derived from hematopoietic organs turn out to immunolabel with the plasmatocyte-specific antibody MS13. The circulating plasmatocytes derived from hematopoietic organs have higher ploidy levels than the granular cells and represent a separate lineage of hemocytes. PMID:14551769

  9. Extraglandular and intraglandular vascularization of canine prostate.

    Science.gov (United States)

    Stefanov, Miroslav

    2004-03-01

    The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism.

  10. Enzyme-linked immunosorbent Assay for detecting of antibody to canine distemper virus

    OpenAIRE

    Sudarisman

    2006-01-01

    Serum neutralisation test (SNT) has been established for evaluating canine distemper vaccination, but until now SNT was rarely used due to the need for continuous tissue culture facilities and requires 3 days to perform. For detecting antibody to canine distemper virus, an enzyme-linked immunosorbent assay (ELISA) is relatively simple and rapid seroassay. ELISA for canine immunoglobulin (Ig) G antibodies to canine distemper virus (CDV) was developed by using Onderstepoort strain of canine dis...

  11. The Hematopoietic Stem Cell Niche—Home for Friend and Foe?

    OpenAIRE

    Daniela S Krause; Scadden, David T.; Preffer, Frederic I.

    2012-01-01

    The hematopoietic stem cell (HSC) niche is involved in the maintainance and regulation of quiescence, self-renewal and differentiation of hematopoietic stem cells and the fate of their progeny in mammals dealing with the daily stresses to the hematopoietic system. From the discovery that perturbations of the HSC niche can lead to hematopoietic disorders, we have now arrived at the prospect that the HSC niche may play a role in hematological malignancies and that this HSC niche may be a target...

  12. Creation of distal canine limb lymphedema

    Energy Technology Data Exchange (ETDEWEB)

    Chen, H.C.; Pribaz, J.J.; O' Brien, B.M.; Knight, K.R.; Morrison, W.A.

    1989-06-01

    A canine model of distal limb lymphedema was established in order to study the treatment of this condition by lymph node transfer. This model was more difficult to establish than whole-limb lymphedema. Significant edema was achieved by a combination of preoperative irradiation and circumferential removal of skin from the irradiated areas followed by removal of the contents of the popliteal fossa. Despite these measures, it was not possible to produce lymphedema in every case, possibly because of the presence of lymphaticovenous shunts and panvascular compensation mechanisms.

  13. Lactoferrin in canine sera: a pyometra study.

    Science.gov (United States)

    Bartoskova, A; Adlerova, L; Kudlackova, H; Leva, L; Vitasek, R; Faldyna, M

    2009-07-01

    The concentration of lactoferrin was measured in canine sera from groups of healthy male dogs as well as pregnant and non-pregnant female dogs and was compared with that of bitches with pyometra. Lactoferrin concentrations were higher in bitches with pyometra. The role of elevated lactoferrin concentrations in the suppression of lymphocyte activity was examined in sera from bitches with pyometra in a series of investigations. Although the sera from bitches with pyometra were capable of suppressing lymphocyte activity, lactoferrin was not found to be involved in this action. PMID:19754566

  14. Definition, Classification, and Pathophysiology of Canine Glaucoma.

    Science.gov (United States)

    Pizzirani, Stefano

    2015-11-01

    Glaucoma is a common ocular condition in humans and dogs leading to optic nerve degeneration and irreversible blindness. Primary glaucoma is a group of spontaneous heterogeneous diseases. Multiple factors are involved in its pathogenesis and these factors vary across human ethnic groups and canine breeds, so the clinical phenotypes are numerous and their classification can be challenging and remain superficial. Aging and oxidative stress are major triggers for the manifestation of disease. Multiple, intertwined inflammatory and biochemical cascades eventually alter cellular and extracellular physiology in the optic nerve and trabecular meshwork and lead to vision loss. PMID:26456751

  15. Enhancing T cell reconstitution after hematopoietic stem cell transplantation: a brief update of the latest trends

    Science.gov (United States)

    Zakrzewski, Johannes L.; Goldberg, Gabrielle L.; Smith, Odette M.; van den Brink, Marcel R.M.

    2009-01-01

    Hematopoietic stem cell transplantation (HSCT) is associated with a period of immune incompetence that particularly affects the T cell lineage. Strategies to enhance T cell reconstitution could significantly improve the survival of HSCT recipients by decreasing the incidence of fatal infectious complications and by enhancing graft-versus-tumor activity. In recent years, a variety of promising strategies have been established in preclinical models to improve T cell recovery in particular after allogeneic T cell-depleted HSCT, without aggravating graft-versus-host disease while preserving or even improving graft-versus-tumor activity. These therapies include treatment with keratinocyte growth factor (KGF), growth hormone (GH), LHRH agonists, interleukin 7 (IL-7) and interleukin 15 (IL-15). Thanks to the establishment of Notch-based culture systems, adoptive cellular therapies with T lineage-committed precursor cells have become feasible, since early T cell progenitors can now easily be generated in vitro in large quantities and have been proven to be very effective in enhancing T cell reconstitution and anti-tumor activity after allogeneic T cell-depleted HSCT. The translation of most of these strategies into clinical trials is likely and in some cases Phase I/II studies are already underway. PMID:17905611

  16. Hematopoietic stem cell transplantation for infantile osteopetrosis.

    Science.gov (United States)

    Orchard, Paul J; Fasth, Anders L; Le Rademacher, Jennifer; He, Wensheng; Boelens, Jaap Jan; Horwitz, Edwin M; Al-Seraihy, Amal; Ayas, Mouhab; Bonfim, Carmem M; Boulad, Farid; Lund, Troy; Buchbinder, David K; Kapoor, Neena; O'Brien, Tracey A; Perez, Miguel A Diaz; Veys, Paul A; Eapen, Mary

    2015-07-01

    We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HLA-mismatched unrelated donors. The median age at transplantation was 12 months. Busulfan and cyclophosphamide was the most common conditioning regimen. Long-term survival was higher after HLA-matched sibling compared to alternative donor transplantation. There were no differences in survival after HLA-mismatched related, HLA-matched unrelated, or mismatched unrelated donor transplantation. The 5- and 10-year probabilities of survival were 62% and 62% after HLA-matched sibling and 42% and 39% after alternative donor transplantation (P = .01 and P = .002, respectively). Graft failure was the most common cause of death, accounting for 50% of deaths after HLA-matched sibling and 43% of deaths after alternative donor transplantation. The day-28 incidence of neutrophil recovery was 66% after HLA-matched sibling and 61% after alternative donor transplantation (P = .49). The median age of surviving patients is 7 years. Of evaluable surviving patients, 70% are visually impaired; 10% have impaired hearing and gross motor delay. Nevertheless, 65% reported performance scores of 90 or 100, and in 17%, a score of 80 at last contact. Most survivors >5 years are attending mainstream or specialized schools. Rates of veno-occlusive disease and interstitial pneumonitis were high at 20%. Though allogeneic transplantation results in long-term survival with acceptable social function, strategies to lower graft failure and hepatic and pulmonary toxicity are urgently needed. PMID:26012570

  17. Hematopoietic stem cell transplantation for infantile osteopetrosis.

    Science.gov (United States)

    Orchard, Paul J; Fasth, Anders L; Le Rademacher, Jennifer; He, Wensheng; Boelens, Jaap Jan; Horwitz, Edwin M; Al-Seraihy, Amal; Ayas, Mouhab; Bonfim, Carmem M; Boulad, Farid; Lund, Troy; Buchbinder, David K; Kapoor, Neena; O'Brien, Tracey A; Perez, Miguel A Diaz; Veys, Paul A; Eapen, Mary

    2015-07-01

    We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HLA-mismatched unrelated donors. The median age at transplantation was 12 months. Busulfan and cyclophosphamide was the most common conditioning regimen. Long-term survival was higher after HLA-matched sibling compared to alternative donor transplantation. There were no differences in survival after HLA-mismatched related, HLA-matched unrelated, or mismatched unrelated donor transplantation. The 5- and 10-year probabilities of survival were 62% and 62% after HLA-matched sibling and 42% and 39% after alternative donor transplantation (P = .01 and P = .002, respectively). Graft failure was the most common cause of death, accounting for 50% of deaths after HLA-matched sibling and 43% of deaths after alternative donor transplantation. The day-28 incidence of neutrophil recovery was 66% after HLA-matched sibling and 61% after alternative donor transplantation (P = .49). The median age of surviving patients is 7 years. Of evaluable surviving patients, 70% are visually impaired; 10% have impaired hearing and gross motor delay. Nevertheless, 65% reported performance scores of 90 or 100, and in 17%, a score of 80 at last contact. Most survivors >5 years are attending mainstream or specialized schools. Rates of veno-occlusive disease and interstitial pneumonitis were high at 20%. Though allogeneic transplantation results in long-term survival with acceptable social function, strategies to lower graft failure and hepatic and pulmonary toxicity are urgently needed.

  18. SBR-Blood: systems biology repository for hematopoietic cells.

    Science.gov (United States)

    Lichtenberg, Jens; Heuston, Elisabeth F; Mishra, Tejaswini; Keller, Cheryl A; Hardison, Ross C; Bodine, David M

    2016-01-01

    Extensive research into hematopoiesis (the development of blood cells) over several decades has generated large sets of expression and epigenetic profiles in multiple human and mouse blood cell types. However, there is no single location to analyze how gene regulatory processes lead to different mature blood cells. We have developed a new database framework called hematopoietic Systems Biology Repository (SBR-Blood), available online at http://sbrblood.nhgri.nih.gov, which allows user-initiated analyses for cell type correlations or gene-specific behavior during differentiation using publicly available datasets for array- and sequencing-based platforms from mouse hematopoietic cells. SBR-Blood organizes information by both cell identity and by hematopoietic lineage. The validity and usability of SBR-Blood has been established through the reproduction of workflows relevant to expression data, DNA methylation, histone modifications and transcription factor occupancy profiles. PMID:26590403

  19. The Genetic Landscape of Hematopoietic Stem Cell Frequency in Mice

    Directory of Open Access Journals (Sweden)

    Xiaoying Zhou

    2015-07-01

    Full Text Available Prior efforts to identify regulators of hematopoietic stem cell physiology have relied mainly on candidate gene approaches with genetically modified mice. Here we used a genome-wide association study (GWAS strategy with the hybrid mouse diversity panel to identify the genetic determinants of hematopoietic stem/progenitor cell (HSPC frequency. Among 108 strains, we observed ∼120- to 300-fold variation in three HSPC populations. A GWAS analysis identified several loci that were significantly associated with HSPC frequency, including a locus on chromosome 5 harboring the homeodomain-only protein gene (Hopx. Hopx previously had been implicated in cardiac development but was not known to influence HSPC biology. Analysis of the HSPC pool in Hopx−/− mice demonstrated significantly reduced cell frequencies and impaired engraftment in competitive repopulation assays, thus providing functional validation of this positional candidate gene. These results demonstrate the power of GWAS in mice to identify genetic determinants of the hematopoietic system.

  20. Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation.

    Science.gov (United States)

    Goode, Debbie K; Obier, Nadine; Vijayabaskar, M S; Lie-A-Ling, Michael; Lilly, Andrew J; Hannah, Rebecca; Lichtinger, Monika; Batta, Kiran; Florkowska, Magdalena; Patel, Rahima; Challinor, Mairi; Wallace, Kirstie; Gilmour, Jane; Assi, Salam A; Cauchy, Pierre; Hoogenkamp, Maarten; Westhead, David R; Lacaud, Georges; Kouskoff, Valerie; Göttgens, Berthold; Bonifer, Constanze

    2016-03-01

    Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development. PMID:26923725

  1. Tumor vaccines

    International Nuclear Information System (INIS)

    Tumor vaccines have several potential advantages over standard anticancer regiments. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tumor vaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which immune tolerance exists. That is why the population of tumor-specific lymphocytes is represented by a small number of low-affinity T-lymphocytes that induce weak antitumor immune response. Simultaneously, tumors evolve many mechanisms to actively evade immune system, what makes them poorly immunogenic or even tolerogenic. Novel immunotherapeutic strategies are directed toward breaking immune tolerance to tumor antigens, enhancing immunogenicity of tumor vaccines and overcoming mechanisms of tumor escape. There are several approaches, unfortunately, all of them still far away from an ideal tumor vaccine that would reject a tumor. Difficulties in the activation of antitumor immune response by tumor vaccines have led to the development of alternative immunotherapeutic strategies that directly focus on effector mechanisms of immune system (adoptive tumor- specific T-lymphocyte transfer and tumor specific monoclonal antibodies). (author)

  2. Interaction of natural killer cells with neutrophils exerts a significant antitumor immunity in hematopoietic stem cell transplantation recipients.

    Science.gov (United States)

    Ueda, Ryosuke; Narumi, Kenta; Hashimoto, Hisayoshi; Miyakawa, Reina; Okusaka, Takuji; Aoki, Kazunori

    2016-01-01

    Autologous hematopoietic stem cell transplantation (HSCT) can induce a strong antitumor immunity by homeostatic proliferation (HP) of T cells and suppression of regulatory T cells following preconditioning-induced lymphopenia. However, the role of innate immunity including natural killer (NK) cells is still not understood. Here, first, we examined whether NK cells exert an antitumor effect after syngeneic HSCT in a murine colon cancer model. Flow cytometry showed that NK cells as well as T cells rapidly proliferated after HSCT, and the frequency of mature NK cells was increased in tumor during HP. Furthermore, NK cells undergoing HP were highly activated, which contributed to substantial tumor suppression. Then, we found that a large number of neutrophils accumulated in tumor early after syngeneic HSCT. It was recently reported that neutrophil-derived mediators modulate NK cell effector functions, and so we examined whether the neutrophils infiltrated in tumor are associated with NK cell-mediated antitumor effect. The depletion of neutrophils significantly impaired an activation of NK cells in tumor and increased the fraction of proliferative NK cells accompanied by a decrease in NK cell survival. The results suggested that neutrophils in tumor prevent NK cells from activation-induced cell death during HP, thus leading to a significant antitumor effect by NK cells. This study revealed a novel aspect of antitumor immunity induced by HSCT and may contribute to the development of an effective therapeutic strategy for cancer using HSCT.

  3. Cone beam computed tomography findings of impacted upper canines

    Energy Technology Data Exchange (ETDEWEB)

    Da Silva Santos, Ludmilla Mota [Dept. of Endodontics, Aracatuba Dental School, Paulista State University, Aracatuba(Brazil); Bastos, Luana Costa; Da Silva, Silvio Jose Albergaria; Campos, Paulo Sergio Flores [School of Dentistry, Federal University of Bahia, Salvador (Brazil); Oliveira Santos, Christiano [Dept. of Stomatology, Oral Public Health, and Forensic Dentistry, School of Dentistry, University of Sao Paulo, Ribeirao Preto (Brazil); Neves, Frederico Sampaio [Dept. of Oral Diagnosis, Piracicaba Dental School, State University of Campinas, Piracicaba (Brazil)

    2014-12-15

    To describe the features of impacted upper canines and their relationship with adjacent structures through three-dimensional cone-beam computed tomography (CBCT) images. Using the CBCT scans of 79 upper impacted canines, we evaluated the following parameters: gender, unilateral/bilateral occurrence, location, presence and degree of root resorption of adjacent teeth (mild, moderate, or severe), root dilaceration, dental follicle width, and presence of other associated local conditions. Most of the impacted canines were observed in females (56 cases), unilaterally (51 cases), and at a palatine location (53 cases). Root resorption in adjacent teeth and root dilaceration were observed in 55 and 47 impacted canines, respectively. In most of the cases, the width of the dental follicle of the canine was normal; it was abnormally wide in 20 cases. A statistically significant association was observed for all variables, except for root dilaceration (p=0.115) and the side of impaction (p=0.260). Root resorption of adjacent teeth was present in most cases of canine impaction, mostly affecting adjacent lateral incisors to a mild degree. A wide dental follicle of impacted canines was not associated with a higher incidence of external root resorption of adjacent teeth.

  4. Cone beam computed tomography findings of impacted upper canines

    International Nuclear Information System (INIS)

    To describe the features of impacted upper canines and their relationship with adjacent structures through three-dimensional cone-beam computed tomography (CBCT) images. Using the CBCT scans of 79 upper impacted canines, we evaluated the following parameters: gender, unilateral/bilateral occurrence, location, presence and degree of root resorption of adjacent teeth (mild, moderate, or severe), root dilaceration, dental follicle width, and presence of other associated local conditions. Most of the impacted canines were observed in females (56 cases), unilaterally (51 cases), and at a palatine location (53 cases). Root resorption in adjacent teeth and root dilaceration were observed in 55 and 47 impacted canines, respectively. In most of the cases, the width of the dental follicle of the canine was normal; it was abnormally wide in 20 cases. A statistically significant association was observed for all variables, except for root dilaceration (p=0.115) and the side of impaction (p=0.260). Root resorption of adjacent teeth was present in most cases of canine impaction, mostly affecting adjacent lateral incisors to a mild degree. A wide dental follicle of impacted canines was not associated with a higher incidence of external root resorption of adjacent teeth.

  5. BURDEN OF ABNORMAL HEMATOPOIETIC CLONE IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodys plastic syndromes (MDS).Methods The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor ( TNF), CD4 + and CD8 + T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed.Results The clone burden of MDS patients was 67.4% ± 36. 2%. MDS clone burden positively correlated with bone marrow blasts (r=0.483, P<0.05), negatively with hemoglobin level (r=-0.445, P<0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (>50%) and low clone burden (≤50%) groups were 7.78%±5.51% and 3.45%±3.34%, 56.06±14. 28 g/L and 76.40±24.44 g/L, (1.82±0.48)×1012/L and (2. 32±0.66)×1012/L, respectively (all P <0.05). CD4 + T lymphocytes of MDS patients and normal controls were (0. 274±0.719)×109/L and (0.455±0.206)×109/L, respectively (P<0.05). CD8 ± T lymphocytes of MDS patients and normal controls were (0.240±0.150)×109/L and (0.305 ±0.145)×109/L, respectively. The serum level of interleukin-2 of MDS patients (6.29±3.58 ng/mL) was significantly higher than normal control (3.11±1.40ng/mL, P<0.05). The serum level of TNF of MDS patients and normal control group were 2.42±1.79 ng/mL and 1.68 ±0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90 ±0.52) than that in low clone burden patients (0.97±0.44, P<0.05).Conclusion The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its

  6. Establishment of a sensitized canine model for kidney transplantation

    Institute of Scientific and Technical Information of China (English)

    XIE Sen; XIA Sui-sheng; TANG Li-gong; CHENG Jun; CHEN Zhi-shui; ZHENG Shan-gen

    2005-01-01

    Objective:To establish a sensitized canine model for kidney transplantation. Methods:12 male dogs were averagely grouped as donors and recipients. A small number of donor canine lymphocytes was infused into different anatomic locations of a paired canine recipient for each time and which was repeated weekly. Specific immune sensitization was monitored by means of Complement Dependent Cytotoxicity (CDC) and Mixed Lymphocyte Culture (MLC) test. When CDC test conversed to be positive and MLC test showed a significant proliferation of reactive lymphocytes of canine recipients, the right kidneys of the paired dogs were excised and transplanted to each other concurrently. Injury of renal allograft function was scheduled determined by ECT dynamic kidney photography and pathologic investigation. Results :CDC test usually conversed to be positive and reactive lymphocytes of canine recipients were also observed to be proliferated significantly in MLC test after 3 to 4 times of canine donor lymphocyte infusions. Renal allograft function deterioration occurred 4 d post-operatively in 4 of 6 canine recipients, in contrast to none in control dogs. Pathologic changes suggested antibody-mediated rejection (delayed) or acute rejection in 3 excised renal allograft of sensitized dogs. Seven days after operation, all sensitized dogs had lost graft function, pathologic changes of which showed that the renal allografts were seriously rejected. 2 of 3 dogs in control group were also acutely rejected. Conclusion:A convenient method by means of repeated stimulation of canine lymphocyte may induce specific immune sensitization in canine recipients. Renal allografts in sensitized dogs will be earlier rejected and result in a more deteriorated graft function.

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

    OpenAIRE

    Shafiee, Radmehr; Javanbakht, Javad; Atyabi, Nahid; Kheradmand, Pegah; Kheradmand, Danial; Bahrami, Alimohammad; Daraei, Hasti; Khadivar, Farshid

    2013-01-01

    Background The human “Elston and Ellis grading method” was utilized in dogs with mammary tumor to examine its relation to prognosis in this species, based on a 2-year follow-up period. Although cytopathology is widely used for early diagnosis of human neoplasms, it is not commonly performed in veterinary medicine. Our objectives in this study were to identify cytopathology criteria of malignancy for canine mammary tumors and the frequency of different types of mammary lesions and their relati...

  8. Detection of canine echinococcosis by coproantigen ELISA

    Institute of Scientific and Technical Information of China (English)

    DeS; PanD; BeraAK; SreevatsavaV; DasSK; DasS; RanaT; BandyopadhyayS; BhattacharyaD

    2010-01-01

    Objective:To study the canine echinococcosis by coproantigen ELISA method. Methods:During the present investigation experimental infection was established using evaginated worms of Echinococcus granulosus (E. granulosus). To check cross reactivity two pups were infected with Taenia hydatigena(T. hydatigena). In order to detect the presence of antigen, hyperimmune sera were raised against excretory-secretory products of adult worms E. chinococcus granulosus. Faecal sample collected either from experimentally infected pups or from other sources were heated at 70℃to detect heat stable soluble antigen. Results:Pups harbouring less than 104 worms showed negative results. Samples collected from 14 days onwards from experimentally infected animals harbouring more than 104 worms showed positive value. The maximum positive samples were detected in samples collected from in and around slaughter house and the least number of samples were detected positive maintained by dog squad. Conclusions:The affinity purified IgG exhibited promising results for detection of canine echinococcosis by indirect ELISA.

  9. Seroepidemiology of Canine parvovirus infection in dogs

    Directory of Open Access Journals (Sweden)

    Indrawati Sendow

    2004-10-01

    Full Text Available Canine parvovirus is an acute and fatal viral disease in dogs. A total of 209 local, cross breed and breed dogs sera from Kodya Bogor, Kabupaten Bogor, Sukabumi, and Jakarta, had been tested using Haemagglutination Inhibition Test (HI with pig red blood cells. A total of 64 breed and cross breed dogs from Sukabumi and Kodya Bogor, were used as a sentinel dogs to study the epidemiology of Canine parvovirus (CPV infection and its immunological responses caused by vaccination. The results indicated that 78% (95 breed and cross bred dogs and 59% (51 local dogs had antibody to CPV. Sentinel dogs results indicated that dogs had been vaccinated showed antibody response with the varied titre dependant upon prevaccination titre. Low prevaccinated titre gave better response than protective level titre. From 19 puppies observed, Maternal antibodi were still detected until 5 weeks old puppies. First vaccination given at less than 3 months old, should be boosted after 3 months old puppied. Antibodi titre produced by natural infection will keep untill 2 years. These data concluded that the dog condition and time of vaccination will affect the optimum antibody response.

  10. A custom made jig for individual canine retraction

    Directory of Open Access Journals (Sweden)

    Vipul Kumar Sharma

    2016-01-01

    Full Text Available We face difficulty in individual canine retraction in the bracket system lacking power arms on the canines. When orthodontic force is applied through the center of resistance (CR, then, tooth translation ensues. Forces applied at a distance from the CR create a moment that tends to rotate and tip the tooth. The tendency of tipping is increased in the bracket system lacking power arm, since, force is applied more occlusally. Hence, we have designed a chair side custom made jig to retract the canines individually.

  11. Canine pluripotent stem cells: Are they ready for clinical applications?

    Directory of Open Access Journals (Sweden)

    Dean Harvey Betts

    2015-10-01

    Full Text Available The derivation of canine embryonic stem cells and generation of canine induced pluripotent stem cells are significant achievements that have unlocked the potential for developing novel cell-based disease models, drug discovery platforms and transplantation therapies in the dog. A progression from concept to cure in this clinically relevant companion animal will not only help our canine patients but also help advance human regenerative medicine. Nevertheless, many issues remain to be resolved before pluripotent cells can be used clinically in a safe and reproducible manner.

  12. Towards immunotherapy with redirected T cells in a large animal model: Ex vivo activation, expansion, and genetic modification of canine T cells

    OpenAIRE

    Mata, Melinda; Vera, Juan; Gerken, Claudia; Rooney, Cliona M; Miller, Tasha; Pfent, Catherine; Wang, Lisa L.; Wilson-Robles, Heather M.; Gottschalk, Stephen

    2014-01-01

    Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has shown promising anti-tumor activity in early phase clinical studies, especially for hematological malignancies. However, most preclinical models do not reliably mimic human disease. We reasoned that developing an adoptive T-cell therapy approach for spontaneous osteosarcoma (OS) occurring in dogs would more closely reproduce the condition in human cancer. To generate CAR-expressing canine T cells we developed expans...

  13. 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.

    Science.gov (United States)

    Mohr, Annika; Lüder Ripoli, Florenza; Hammer, Susanne Conradine; Willenbrock, Saskia; Hewicker-Trautwein, Marion; Kiełbowicz, Zdzisław; Murua Escobar, Hugo; Nolte, Ingo

    2016-01-01

    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. PMID:27649560

  14. Clinical and serological response of wild dogs (Lycaon pictus to vaccination against canine distemper, canine parvovirus infection and rabies

    Directory of Open Access Journals (Sweden)

    J. Van Heerden

    2002-07-01

    Full Text Available Wild dogs Lycaon pictus (n = 8 were vaccinated 4 times against canine distemper (n = 8 (initially with inactivated and subsequently with live attenuated strains of canine distemper and canine parvovirus infection (n = 8 over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use in domestic dogs, were used. None of the vaccinated dogs showed any untoward clinical signs. The inactivated canine distemper vaccine did not result in seroconversion whereas the attenuated live vaccine resulted in seroconversion in all wild dogs. Presumably protective concentrations of antibodies to canine distemper virus were present in all wild dogs for at least 451 days. Canine parvovirus haemagglutination inhibition titres were present in all wild dogs prior to the administration of vaccine and protective concentrations persisted for at least 451 days. Vaccination against parvovirus infection resulted in a temporary increase in canine parvovirus haemagglutination inhibition titres in most dogs. Administration of both inactivated parenteral and live oral rabies vaccine initially resulted in seroconversion in 7 of 8 dogs. These titres, however, dropped to very low concentrations within 100 days. Booster administrations resulted in increased antibody concentrations in all dogs. It was concluded that the vaccines were safe to use in healthy subadult wild dogs and that a vaccination protocol in free-ranging wild dogs should at least incorporate booster vaccinations against rabies 3-6 months after the first inoculation.

  15. TVT NASAL –Tumor Venéreo Transmissível- um caso clínico

    Directory of Open Access Journals (Sweden)

    CANAL, Ivo Hellmeister; DAGLI, Maria Lucia Zaidan; TORRES, Luciana Neves; PIVETA , Lidiana Cândida; CANAL, Raoní Bertelli.

    2005-02-01

    Full Text Available The authors do a revision of CTVT - Canine Transmissible Venereal Tumor – clinic, diagnostic and treatment from a clinical case in nasal cavity and describes a complete protocol for the treatment using biotechniques and anti-tumor medication. Vincristine and ciclofosfamide like chemotherapeutic management and anti-tumor medication, and Interferon in low and oral doses with Levamisol, immune modulator, like a biotherapy. A bibliography revision. This description is the most recent and complete treatment used by the clinic.

  16. Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells

    OpenAIRE

    Gschweng, Eric Hans

    2015-01-01

    Engineering the immune system against cancer ideally provides surgical precision against the antigen bearing target cell while avoiding the systemic, off-target toxicity of chemotherapy. Successful treatment of patients in the clinic has been achieved by the expression of anti-cancer T-cell receptors (TCR) and chimeric antigen receptors (CAR) in T cells followed by infusion of these cells into cancer patients. Unfortunately, while many patients initially respond showing anti-tumor efficacy, t...

  17. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  18. Odontogenic Tumors

    OpenAIRE

    TAHSİNOĞLU, Melih

    2013-01-01

    DefinitionThe neoplasms that consist of the cells considered specialized for odontogenesis, and their product (dentin, enamel, cementum) are called odontogenic tumors.ClassificationTo initiate odontogenesis, epithelium is a must. Same rule holds for the odontogenic tumors: without odontogenic epithelium, odontogenic tumors cannot be, without the induction of odontogenic epithelium odontogenic mesenchyme cannot develop.

  19. Tumor Markers

    Science.gov (United States)

    ... guidelines on a variety of topics, including tumor markers for breast cancer, colorectal cancer, lung cancer, and others. The ... of recurrence 70-Gene signature (Mammaprint®) Cancer type: Breast ... Can tumor markers be used in cancer screening? Because tumor markers ...

  20. Case Report: Canine Fossa Abscess; A Rare Etiological Factor: The Lower Canine Tooth

    OpenAIRE

    Agacayak, K. Serkan; Atılgan, S. Serhat; GORGUN, Belgin; Yaman, Ferhan; Ucan, M. Can; Atalay, Yusuf

    2013-01-01

    Odontogenic infection may be dangerous; especially when life-threatening complications occur. Infection spreads through the bone and periosteum toward nearby or more distant structures and spaces. Canine fossa abscess is an odontogenic infection that can lead to life-threatening complications. Successful treatment requires early recognition, determination of etiological factors, and proper medical and surgical management. The aim of this paper is to emphasize different and rare etiological fa...

  1. Challenges in circulating tumor cell detection by the CellSearch system

    NARCIS (Netherlands)

    Andree, K.C.; Dalum, van G.; Terstappen, L.W.M.M.

    2016-01-01

    Enumeration and characterization of circulating tumor cells (CTC) hold the promise of a real time liquid biopsy. They are however present in a large background of hematopoietic cells making their isolation technically challenging. In 2004, the CellSearch system was introduced as the first and only F

  2. Comparative Study of Human Hematopoietic Cell Engraftment into Balb/c and C57BL/6 Strain of Rag-2/Jak3 Double-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Ayumi Ono

    2011-01-01

    Full Text Available Immunodeficient mice are becoming invaluable tools in human stem cell and tumor research. In this study, we generated Rag-2/Jak3 double-deficient (Rag-2−/−Jak3−/− mice with a C57/BL6 and Balb/c genetic background and compared the human lymphohematopoietic cell engraftment rate. Human cord blood-derived CD34+ hematopoietic stem cells were successfully engrafted into Balb/c Rag-2−/−Jak3−/− mice; however, the engraftment rate was far lower in C57/BL6 Rag-2−/−Jak3−/− mice. Transplantation of human peripheral blood mononuclear cells resulted in the same tendency. Thus, a Balb/c background offers superior engraftment capacity than a C57/BL6 background and provides an attractive model for human hematopoietic cell engraftment.

  3. Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity.

    Science.gov (United States)

    Di Biase, Stefano; Lee, Changhan; Brandhorst, Sebastian; Manes, Brianna; Buono, Roberta; Cheng, Chia-Wei; Cacciottolo, Mafalda; Martin-Montalvo, Alejandro; de Cabo, Rafael; Wei, Min; Morgan, Todd E; Longo, Valter D

    2016-07-11

    Immune-based interventions are promising strategies to achieve long-term cancer-free survival. Fasting was previously shown to differentially sensitize tumors to chemotherapy while protecting normal cells, including hematopoietic stem and immune cells, from its toxic side effects. Here, we show that the combination of chemotherapy and a fasting-mimicking diet (FMD) increases the levels of bone marrow common lymphoid progenitor cells and cytotoxic CD8(+) tumor-infiltrating lymphocytes (TILs), leading to a major delay in breast cancer and melanoma progression. In breast tumors, this effect is partially mediated by the downregulation of the stress-responsive enzyme heme oxygenase-1 (HO-1). These data indicate that FMD cycles combined with chemotherapy can enhance T cell-dependent targeted killing of cancer cells both by stimulating the hematopoietic system and by enhancing CD8(+)-dependent tumor cytotoxicity. PMID:27411588

  4. The role of dendritic cells in graft-versus-tumor effect

    Directory of Open Access Journals (Sweden)

    Pavan eReddy

    2014-02-01

    Full Text Available Dendritic cells (DCs are the most potent antigen presenting cells (APCs. DCs play a pivotal role in determining the character and magnitude of immune responses to tumors. Host and donor hematopoietic derived DCs play a critical role in the development of graft-versus host disease (GVHD following allogeneic hematopoietic cell transplantation (allo-HCT. GVHD is tightly linked with the graft-versus-tumor (GVT effect. Although both host and donor DCs are important regulators of GVHD, the role of DCs in GVT is poorly understood. GVT is caused by donor T cells that attack recipient tumor cells. The donor T cells recognize alloantigens and tumor specific antigens (TSAs are mediating GVHD. The process of presentation of these antigens, especially TSAs remains unknown. Recent data suggested that DC may be essential role for inducing GVT. The mechanisms that DCs possess may include direct presentation, cross-presentation, cross-dressing. . The role they play in GVT will be reviewed.

  5. Emerging perspectives on hereditary glomerulopathies in canines

    Directory of Open Access Journals (Sweden)

    Littman MP

    2015-04-01

    Full Text Available Meryl P LittmanDepartment of Clinical Studies – Philadelphia, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USAAbstract: Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spontaneous cases of glomerular disease are good models for their human counterparts. The dogs present clinically with protein-losing nephropathy and variable signs of hypertension, thromboembolic events, edema/effusions/nephrotic syndrome, or eventually with signs of renal disease such as anorexia, vomiting, weight loss, and/or polyuria/polydipsia. Laboratory changes include proteinuria, hypoalbuminemia, hypercholesterolemia, and eventually azotemia, hyperphosphatemia, anemia, and isosthenuria. Renal biopsies examined with transmission electron microscopy, immunofluorescence, and thin section light microscopy may show ultrastructural glomerular basement membrane abnormalities, glomerulosclerosis, amyloidosis, non-amyloid fibrillary deposition, or breed-associated predispositions for immune-complex glomerulonephritis. Genome-wide association studies and fine sequencing of candidate genes have led to the discovery of variant alleles associated with disease in some breeds; eg, 1 glomerular basement membrane ultrastructural abnormalities due to defective collagen type IV, caused by different premature stop codons in each of four breeds; ie, in COL4A5 in Samoyeds and Navasota mix breed dogs (X-linked, and in COL4A4 in English Cocker Spaniels and English Springer Spaniels (autosomal recessive; and 2 glomerulosclerosis-related podocytopathy with slit diaphragm protein anomalies of both nephrin and Neph3/filtrin due to non-synonymous single nucleotide polymorphisms in conserved regions of their encoding genes, NPHS1 and KIRREL2, in Soft Coated Wheaten Terriers and Airedale Terriers, with a complex mode of inheritance. Age at onset and progression to end-stage renal disease vary depending on the model. Genetic

  6. Longitudinal Assessment of Hematopoietic Stem Cell Transplantation and Hyposalivation

    DEFF Research Database (Denmark)

    Laaksonen, Matti; Ramseier, Adrian; Rovó, Alicia;

    2011-01-01

    Hyposalivation is a common adverse effect of anti-neoplastic therapy of head and neck cancer, causing impaired quality of life and predisposition to oral infections. However, data on the effects of hematopoietic stem cell transplantation (HSCT) on salivary secretion are scarce. The present study...

  7. Sexual function 1-year after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Noerskov, K H; Schjødt, I; Syrjala, K L;

    2016-01-01

    Treatment with allogeneic hematopoietic stem cell transplantation (HSCT) is associated with short and long-term toxicities that can result in alterations in sexual functioning. The aims of this prospective evaluation were to determine: (1) associations between HSCT and increased sexual dysfunction...

  8. Lentiviral hematopoietic stem cell gene therapy in inherited metabolic disorders

    NARCIS (Netherlands)

    G. Wagemaker (Gerard)

    2014-01-01

    textabstractAfter more than 20 years of development, lentiviral hematopoietic stem cell gene therapy has entered the stage of initial clinical implementation for immune deficiencies and storage disorders. This brief review summarizes the development and applications, focusing on the lysosomal enzyme

  9. Primary Immunodeficiency Diseases and Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Ayse Ozkan

    2014-02-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is the only curative therapy for primary immunodeficiency diseases. Early diagnosis, including prenatally, and early transplantation improve HSCT outcomes. Survival rates improve with advances in the methods of preparing hosts and donor cells, and in supportive and conditioning regimes.

  10. Cellular barcoding tool for clonal analysis in the hematopoietic system

    NARCIS (Netherlands)

    Gerrits, Alice; Dykstra, Brad; Kalmykowa, Olga J.; Klauke, Karin; Verovskaya, Evgenia; Broekhuis, Mathilde J. C.; de Haan, Gerald; Bystrykh, Leonid V.

    2010-01-01

    Clonal analysis is important for many areas of hematopoietic stem cell research, including in vitro cell expansion, gene therapy, and cancer progression and treatment. A common approach to measure clonality of retrovirally transduced cells is to perform integration site analysis using Southern blott

  11. Polycomb group proteins in hematopoietic stem cell aging and malignancies

    NARCIS (Netherlands)

    Klauke, Karin; de Haan, Gerald

    2011-01-01

    Protection of the transcriptional "stemness" network is important to maintain a healthy hematopoietic stem cells (HSCs) compartment during the lifetime of the organism. Recent evidence shows that fundamental changes in the epigenetic status of HSCs might be one of the driving forces behind many age-

  12. A new image of the hematopoietic stem cell vascular niche

    OpenAIRE

    Silberstein, Leslie E.; Lin, Charles P.

    2013-01-01

    The microenvironment within the bone marrow that maintains hematopoietic stem cell (HSC) quiescence is the subject of intense study. In a recent Nature paper, Kunisaki et al combine imaging techniques and computational modeling to define a novel arteriolar niche for quiescent HSCs within the bone marrow.

  13. Placenta as a source of hematopoietic stem cells

    NARCIS (Netherlands)

    E.A. Dzierzak (Elaine); C. Robin (Catherine)

    2010-01-01

    textabstractThe placenta is a large, highly vascularised hematopoietic tissue that functions during the embryonic and foetal development of eutherian mammals. Although recognised as the interface tissue important in the exchange of oxygen, nutrients and waste products between the foetus and mother,

  14. Fetal liver stromal cells promote hematopoietic cell expansion

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Kun; Hu, Caihong [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Zhou, Zhigang [Shanghai 1st People Hospital, Shanghai Jiao Tong University, Shanghai 201620 (China); Huang, Lifang; Liu, Wenli [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China); Sun, Hanying, E-mail: shanhum@163.com [Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030 (China)

    2009-09-25

    Future application of hematopoietic stem and progenitor cells (HSPCs) in clinical therapies largely depends on their successful expansion in vitro. Fetal liver (FL) is a unique hematopoietic organ in which hematopoietic cells markedly expand in number, but the mechanisms involved remain unclear. Stromal cells (StroCs) have been suggested to provide a suitable cellular environment for in vitro expansion of HSPCs. In this study, murine StroCs derived from FL at E14.5, with a high level of Sonic hedgehog (Shh) and Wnt expression, were found to have an increased ability to support the proliferation of HSPCs. This effect was inhibited by blocking Shh signaling. Supplementation with soluble Shh-N promoted the proliferation of hematopoietic cells by activating Wnt signaling. Our findings suggest that FL-derived StroCs support proliferation of HSPCs via Shh inducing an autocrine Wnt signaling loop. The use of FL-derived StroCs and regulation of the Shh pathway might further enhance HPSC expansion.

  15. Lung function after allogeneic hematopoietic stem cell transplantation in children

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Larsen Bang, Cæcilie; Christensen, Ib Jarle;

    2013-01-01

    Reduction in pulmonary function (PF) has been reported in up to 85% of pediatric patients during the first year after hematopoietic stem cell transplantation (HSCT). Our understanding of the etiology for this decrease in lung function is, however, sparse. The aim of this study was to describe PF...

  16. Instruction of hematopoietic lineage choice by cytokine signaling

    Energy Technology Data Exchange (ETDEWEB)

    Endele, Max; Etzrodt, Martin; Schroeder, Timm, E-mail: timm.schroeder@bsse.ethz.ch

    2014-12-10

    Hematopoiesis is the cumulative consequence of finely tuned signaling pathways activated through extrinsic factors, such as local niche signals and systemic hematopoietic cytokines. Whether extrinsic factors actively instruct the lineage choice of hematopoietic stem and progenitor cells or are only selectively allowing survival and proliferation of already intrinsically lineage-committed cells has been debated over decades. Recent results demonstrated that cytokines can instruct lineage choice. However, the precise function of individual cytokine-triggered signaling molecules in inducing cellular events like proliferation, lineage choice, and differentiation remains largely elusive. Signal transduction pathways activated by different cytokine receptors are highly overlapping, but support the production of distinct hematopoietic lineages. Cellular context, signaling dynamics, and the crosstalk of different signaling pathways determine the cellular response of a given extrinsic signal. New tools to manipulate and continuously quantify signaling events at the single cell level are therefore required to thoroughly interrogate how dynamic signaling networks yield a specific cellular response. - Highlights: • Recent studies provided definite proof for lineage-instructive action of cytokines. • Signaling pathways involved in hematopoietic lineage instruction remain elusive. • New tools are emerging to quantitatively study dynamic signaling networks over time.

  17. DNA Damage Response in Hematopoietic Stem Cell Ageing.

    Science.gov (United States)

    Li, Tangliang; Zhou, Zhong-Wei; Ju, Zhenyu; Wang, Zhao-Qi

    2016-06-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing. PMID:27221660

  18. Expansion of human cord blood hematopoietic stem cells for transplantation.

    Science.gov (United States)

    Chou, Song; Chu, Pat; Hwang, William; Lodish, Harvey

    2010-10-01

    A recent Science paper reported a purine derivative that expands human cord blood hematopoietic stem cells in culture (Boitano et al., 2010) by antagonizing the aryl hydrocarbon receptor. Major problems need to be overcome before ex vivo HSC expansion can be used clinically.

  19. DNA Damage Response in Hematopoietic Stem Cell Ageing

    Institute of Scientific and Technical Information of China (English)

    Tangliang Li; Zhong-Wei Zhou; Zhenyu Ju; Zhao-Qi Wang

    2016-01-01

    Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employ-ing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically reg-ulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.

  20. Death of a wild wolf from canine parvovirus enteritis

    Science.gov (United States)

    Mech, L.D.; Kurtz, H.J.; Goyal, S.

    1997-01-01

    A 9-mo-old female wolf (Canis lupus) in the Superior National Forest of Minnesota (USA) died from a canine parvovirus (CPV) infection. This is the first direct evidence that this infection effects free-ranging wild wolves.

  1. Canine index – A tool for sex determination

    Directory of Open Access Journals (Sweden)

    Shankar M. Bakkannavar

    2015-12-01

    Full Text Available Teeth are most useful tools in victim identification in the living as well as the dead in the field of forensic investigations. Their ability to survive in situations like mass disasters makes them constructive devices. Many authors have measured crowns of teeth in both males and females and found certain variations. Canines, reported to survive in air crash and hurricane disasters, are perhaps the most stable teeth in the oral cavity because of the labiolingual thickness of the crown and the root anchorage in the alveolar process of jaws. Measurement of mesiodistal width of the mandibular canines and inter-canine distance of the mandible provides good evidence of sex identification due to dimorphism. This study was undertaken to evaluate the effectiveness of canine index (CI in the determination of sex.

  2. Periodontal ligament distraction: A simplified approach for rapid canine retraction

    Directory of Open Access Journals (Sweden)

    K C Prabhat

    2012-01-01

    Full Text Available Distraction osteogenesis is a method of inducing new bone formation by applying mechanical strains on preexisting bone. The process of osteogenesis in the periodontal ligament during orthodontic tooth movement is similar to the osteogenesis in the midpalatal suture during rapid palatal expansion. A new concept of "distracting the periodontal ligament" is proposed to elicit rapid canine retraction in two weeks. At the time of first premolar extraction, the interseptal bone distal to the canine was undermined with a bone bur, grooving vertically inside the extraction socket along the buccal and lingual sides and extending obliquely toward the socket base. Then, a tooth-borne, custom-made, intraoral distraction device was placed to distract the canine distally into the extraction space. It was activated 0.5 mm/day, immediately after the extraction. Canine was distracted 6.5 mm into the extraction space within two weeks.

  3. Severe canine distemper outbreak in unvaccinated dogs in Mozambique

    Directory of Open Access Journals (Sweden)

    Julieta Zacarias

    2016-02-01

    Full Text Available Although significant animal suffering caused by preventable diseases is frequently seen in developing countries, reports of this are scarce. This report describes avoidable animal suffering owing to a suspected canine distemper (CD outbreak in unvaccinated dogs owned by low-income families in Mozambique that killed approximately 200 animals. Affected dogs exhibited clinical signs, and gross and microscopic lesions compatible with CD. Immunohistochemical staining confirmed the presence of canine distemper virus (CDV in the kidney of one dog from the cohort. This brief communication again illustrates that large outbreaks of CDV in unvaccinated dogs occur and that large-scale avoidable suffering and threats to the health of dogs and wild canines continue. Mass vaccination supported by government and non-government organisations is recommended.Keywords: Canine distemper; dogs; outbreak; animal welfare; Mozambique

  4. Identification of myeloid derived suppressor cells in the peripheral blood of tumor bearing dogs

    Directory of Open Access Journals (Sweden)

    Sherger Matthew

    2012-10-01

    Full Text Available Abstract Background Myeloid derived suppressor cells (MDSCs are a recently described population of immune cells that significantly contribute to the immunosuppression seen in cancer patients. MDSCs are one of the most important factors that limit the efficacy of cancer immunotherapy (e.g. cancer vaccines and MDSC levels are increased in cancer in multiple species. Identifying and targeting MDSCs is actively being investigated in the field of human oncology and is increasingly being investigated in veterinary oncology. The treatment of canine cancer not only benefits dogs, but is being used for translational studies evaluating and modifcying candidate therapies for use in humans. Thus, it is necessary to understand the immune alterations seen in canine cancer patients which, to date, have been relatively limited. This study investigates the use of commercially available canine antibodies to detect an immunosuppressive (CD11blow/CADO48low cell population that is increased in the peripheral blood of tumor-bearing dogs. Results Commercially available canine antibodies CD11b and CADO48A were used to evaluate white blood cells from the peripheral blood cells of forty healthy control dogs and forty untreated, tumor-bearing dogs. Tumor-bearing dogs had a statistically significant increase in CD11blow/CADO48Alow cells (7.9% as compared to the control dogs (3.6%. Additionally, sorted CD11blow/CADO48Alow generated in vitro suppressed the proliferation of canine lymphocytes. Conclusions The purpose of this study was aimed at identifying potential canine specific markers for identifying MDSCs in the peripheral blood circulation of dogs. This study demonstrates an increase in a unique CD11blow/CADO48Alow cell population in tumor-bearing dogs. This immunophenotype is consistent with described phenotypes of MDSCs in other species (i.e. mice and utilizes commercially available canine-specific antibodies. Importantly, CD11blow/CADO48Alow from a tumor environment

  5. Mechanisms of Drug Resistance in Veterinary Oncology— A Review with an Emphasis on Canine Lymphoma

    Directory of Open Access Journals (Sweden)

    Maurice Zandvliet

    2015-08-01

    Full Text Available Drug resistance (DR is the major limiting factor in the successful treatment of systemic neoplasia with cytotoxic chemotherapy. DR can be either intrinsic or acquired, and although the development and clinical implications are different, the underlying mechanisms are likely to be similar. Most causes for DR are pharmacodynamic in nature, result from adaptations within the tumor cell and include reduced drug uptake, increased drug efflux, changes in drug metabolism or drug target, increased capacity to repair drug‐induced DNA damage or increased resistance to apoptosis. The role of active drug efflux transporters, and those of the ABC‐transporter family in particular, have been studied extensively in human oncology and to a lesser extent in veterinary medicine. Methods reported to assess ABC‐transporter status include detection of the actual protein (Western blot, immunohistochemistry, mRNA or ABC‐transporter function. The three major ABC‐transporters associated with DR in human oncology are ABCB1 or P‐gp, ABCC1 or MRP1, and ABCG2 or BCRP, and have been demonstrated in canine cell lines, healthy dogs and dogs with cancer. Although this supports a causative role for these ABC‐transporters in DR cytotoxic agents in the dog, the relative contribution to the clinical phenotype of DR in canine cancer remains an area of debate and requires further prospective studies.

  6. Establishment and Characterization of New Canine and Feline Osteosarcoma Primary Cell Lines

    Directory of Open Access Journals (Sweden)

    Florian R. L. Meyer

    2016-06-01

    Full Text Available Osteosarcomas are the most abundant form of bone malignancies in multiple species. Canine osteosarcomas are considered a valuable model for human osteosarcomas because of their similar features. Feline osteosarcomas, on the other hand, are rarely studied but have interesting characteristics, such as a better survival prognosis than dogs or humans, and less likelihood of metastasis. To enable experimental approaches to study these differences we have established five new canine osteosarcoma cell lines out of three tumors, COS_1186h, COS_1186w, COS_1189, and COS_1220, one osteosarcoma-derived lung metastasis, COS_1033, and two new feline osteosarcoma cell lines, FOS_1077 and FOS_1140. Their osteogenic and neoplastic origin, as well as their potential to produce calcified structures, was determined by the markers osteocalcin, osteonectin, tissue unspecific alkaline phosphatase, p53, cytokeratin, vimentin, and alizarin red. The newly developed cell lines retained most of their markers in vitro but only spontaneously formed spheroids produced by COS_1189 showed calcification in vitro.

  7. Canine distemper virus in Lake Baikal seals (Phoca sibirica).

    OpenAIRE

    Mamaev, L.V.; Visser, Ilona; Belikov, S.I.; Denikina, N.N.; Harder, Timm; Goatley, L.; Rima, B.; Edginton, B.; Osterhaus, Albert; Barrett, Thomas,

    1996-01-01

    textabstractThe virus epizootic which resulted in significant mortality in Siberian seals (Phoca sibirica) in Lake Baikal during 1987/88 was caused by canine distemper virus. Sequence analysis of the virus glycoprotein genes revealed that it was most closely related to recent European field isolates of canine distemper virus. This paper presents evidence that the same virus continued to circulate in seals in Lake Baikal after the initial epizootic. Three out of 45 brain tissue samples collect...

  8. Immunopathogenic and Neurological Mechanisms of Canine Distemper Virus

    OpenAIRE

    Otávio Valério Carvalho; Clarisse Vieira Botelho; Caroline Gracielle Torres Ferreira; Paulo Oldemar Scherer; Jamária Adriana Pinheiro Soares-Martins; Márcia Rogéria de Almeida; Abelardo Silva Júnior

    2012-01-01

    Canine distemper is a highly contagious viral disease caused by the canine distemper virus (CDV), which is a member of the Morbillivirus genus, Paramyxoviridae family. Animals that most commonly suffer from this disease belong to the Canidae family; however, the spectrum of natural hosts for CDV also includes several other families of the order Carnivora. The infectious disease presents worldwide distribution and maintains a high incidence and high levels of lethality, despite the availabilit...

  9. Characterization of a Canine Homolog of Human Aichivirus▿

    OpenAIRE

    Kapoor, A; Simmonds, P.; Dubovi, E J; Qaisar, N.; Henriquez, J. A.; J. Medina; S Shields; Lipkin, W. I.

    2011-01-01

    Many of our fatal "civilization" infectious diseases have arisen from domesticated animals. Although picornaviruses infect most mammals, infection of a companion animal is not known. Here we describe the identification and genomic characterization of the first canine picornavirus. Canine kobuvirus (CKoV), identified in stool samples from dogs with diarrhea, has a genomic organization typical of a picornavirus and encodes a 2,469-amino-acid polyprotein flanked by 5' and 3' untranslated regions...

  10. Permanent Maxillary Canine Agenesis: A Rare Case Report

    OpenAIRE

    Halaswamy V Kambalimath; Jain, Somya; Patil, Raju Umaji; Asokan, Alexander; Kambalimath, Deepashri

    2015-01-01

    ABSTRACT Congenitally missing teeth (CMT) are among one of the commonly known dental anomalies. The most frequently missing teeth in the permanent dentition, excluding the third molars, are mandibular second premolars and maxillary lateral incisors. Exclusive agenesis of both maxillary canines is an extremely rare occurrence and only a few cases have been reported. Previous studies showed that the prevalence of maxillary canine agenesis varies between 0.07 and 0.13%. In recent studies on Indi...

  11. Genomic instability and telomere fusion of canine osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Junko Maeda

    Full Text Available Canine osteosarcoma (OSA is known to present with highly variable and chaotic karyotypes, including hypodiploidy, hyperdiploidy, and increased numbers of metacentric chromosomes. The spectrum of genomic instabilities in canine OSA has significantly augmented the difficulty in clearly defining the biological and clinical significance of the observed cytogenetic abnormalities. In this study, eight canine OSA cell lines were used to investigate telomere fusions by fluorescence in situ hybridization (FISH using a peptide nucleotide acid probe. We characterized each cell line by classical cytogenetic studies and cellular phenotypes including telomere associated factors and then evaluated correlations from this data. All eight canine OSA cell lines displayed increased abnormal metacentric chromosomes and exhibited numerous telomere fusions and interstitial telomeric signals. Also, as evidence of unstable telomeres, colocalization of γ-H2AX and telomere signals in interphase cells was observed. Each cell line was characterized by a combination of data representing cellular doubling time, DNA content, chromosome number, metacentric chromosome frequency, telomere signal level, cellular radiosensitivity, and DNA-PKcs protein expression level. We have also studied primary cultures from 10 spontaneous canine OSAs. Based on the observation of telomere aberrations in those primary cell cultures, we are reasonably certain that our observations in cell lines are not an artifact of prolonged culture. A correlation between telomere fusions and the other characteristics analyzed in our study could not be identified. However, it is important to note that all of the canine OSA samples exhibiting telomere fusion utilized in our study were telomerase positive. Pending further research regarding telomerase negative canine OSA cell lines, our findings may suggest telomere fusions can potentially serve as a novel marker for canine OSA.

  12. Canine Evolution in Sabretoothed Carnivores: Natural Selection or Sexual Selection?

    OpenAIRE

    Marcela Randau; Chris Carbone; Turvey, Samuel T.

    2013-01-01

    The remarkable elongated upper canines of extinct sabretoothed carnivorous mammals have been the subject of considerable speculation on their adaptive function, but the absence of living analogues prevents any direct inference about their evolution. We analysed scaling relationships of the upper canines of 20 sabretoothed feliform carnivores (Nimravidae, Barbourofelidae, Machairodontinae), representing both dirk-toothed and scimitar-toothed sabretooth ecomorphs, and 33 non-sabretoothed felids...

  13. Recent epidemiological status of canine viral enteric infections and Giardia infection in Japan.

    Science.gov (United States)

    Mochizuki, M; Hashimoto, M; Ishida, T

    2001-05-01

    Epidemiology of canine enteric infections was studied. Rectal swabs collected from 95 dogs presented at animal hospitals during a period from January to June of 2000 were examined for enteric pathogens, including viruses and Giardia lamblia (G. lamblia). Most frequently detected in both diarrheal and normal feces were canine coronavirus (55.4%) and G. lamblia (48.2%). Canine parvovirus type 2 (CPV-2) was specifically associated with diarrheal cases and CPV-2b was the predominant antigenic type. Although canine rotavirus, canine adenovirus, and canine distemper virus were also detected in a small number of diarrheal cases, no evidence for calicivirus infection was obtained. PMID:11411507

  14. Transmigration of mandibular canine: report of four cases and review of literature.

    Science.gov (United States)

    Sharma, Gaurav; Nagpal, Archna

    2011-01-01

    Transmigration of canine is a rare phenomenon. The prevalence of transmigration of mandibular canine has been found to be only 0.14%-0.31%. The treatment of impacted transmigrated canine is very complicated if it is diagnosed at a later stage. We report 4 cases of transmigration of mandibular canine and review the literature regarding the etiology and treatment. Panoramic radiograph should be taken during the mixed dentition period if the mandibular canine has not erupted from more than one year from its normal chronological age of eruption as intraoral periapical radiograph examination will not always detect an impacted or transmigrated canine. PMID:22570797

  15. Transmigration of Mandibular Canine: Report of Four Cases and Review of Literature

    Directory of Open Access Journals (Sweden)

    Gaurav Sharma

    2011-01-01

    Full Text Available Transmigration of canine is a rare phenomenon. The prevalence of transmigration of mandibular canine has been found to be only 0.14%–0.31%. The treatment of impacted transmigrated canine is very complicated if it is diagnosed at a later stage. We report 4 cases of transmigration of mandibular canine and review the literature regarding the etiology and treatment. Panoramic radiograph should be taken during the mixed dentition period if the mandibular canine has not erupted from more than one year from its normal chronological age of eruption as intraoral periapical radiograph examination will not always detect an impacted or transmigrated canine.

  16. Symptoms after hospital discharge following hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Gamze Oguz

    2014-01-01

    Full Text Available Aims: The purposes of this study were to assess the symptoms of hematopoietic stem cell transplant patients after hospital discharge, and to determine the needs of transplant patients for symptom management. Materials and Methods: The study adopted a descriptive design. The study sample comprised of 66 hematopoietic stem cell transplant patients. The study was conducted in Istanbul. Data were collected using Patient Information Form and Memorial Symptom Assessment Scale (MSAS. Results: The frequency of psychological symptoms in hematopoietic stem cell transplant patients after discharge period (PSYCH subscale score 2.11 (standard deviation (SD = 0.69, range: 0.93-3.80 was higher in hematopoietic stem cell transplant patients than frequency of physical symptoms (PHYS subscale score: 1.59 (SD = 0.49, range: 1.00-3.38. Symptom distress caused by psychological and physical symptoms were at moderate level (Mean = 1.91, SD = 0.60, range: 0.95-3.63 and most distressing symptoms were problems with sexual interest or activity, difficulty sleeping, and diarrhea. Patients who did not have an additional chronic disease obtained higher MSAS scores. University graduates obtained higher Global Distress Index (GDI subscale and total MSAS scores with comparison to primary school graduates. Total MSAS, MSAS-PHYS subscale, and MSAS-PSYCH subscale scores were higher in patients with low level of income (P < 0.05. The patients (98.5% reported to receive education about symptom management after hospital discharge. Conclusions: Hematopoietic stem cell transplant patients continue to experience many distressing physical or psychological symptoms after discharge and need to be supported and educated for the symptom management.

  17. Canine vector-borne diseases in Brazil

    Directory of Open Access Journals (Sweden)

    Dantas-Torres Filipe

    2008-08-01

    Full Text Available Abstract Canine vector-borne diseases (CVBDs are highly prevalent in Brazil and represent a challenge to veterinarians and public health workers, since some diseases are of great zoonotic potential. Dogs are affected by many protozoa (e.g., Babesia vogeli, Leishmania infantum, and Trypanosoma cruzi, bacteria (e.g., Anaplasma platys and Ehrlichia canis, and helminths (e.g., Dirofilaria immitis and Dipylidium caninum that are transmitted by a diverse range of arthropod vectors, including ticks, fleas, lice, triatomines, mosquitoes, tabanids, and phlebotomine sand flies. This article focuses on several aspects (etiology, transmission, distribution, prevalence, risk factors, diagnosis, control, prevention, and public health significance of CVBDs in Brazil and discusses research gaps to be addressed in future studies.

  18. Canine distemper in endangered Ethiopian wolves.

    Science.gov (United States)

    Gordon, Christopher H; Banyard, Ashley C; Hussein, Alo; Laurenson, M Karen; Malcolm, James R; Marino, Jorgelina; Regassa, Fekede; Stewart, Anne-Marie E; Fooks, Anthony R; Sillero-Zubiri, Claudio

    2015-05-01

    The Ethiopian wolf (Canis simensis) is the world's rarest canid; ≈500 wolves remain. The largest population is found within the Bale Mountains National Park (BMNP) in southeastern Ethiopia, where conservation efforts have demonstrated the negative effect of rabies virus on wolf populations. We describe previously unreported infections with canine distemper virus (CDV) among these wolves during 2005-2006 and 2010. Death rates ranged from 43% to 68% in affected subpopulations and were higher for subadult than adult wolves (83%-87% vs. 34%-39%). The 2010 CDV outbreak started 20 months after a rabies outbreak, before the population had fully recovered, and led to the eradication of several focal packs in BMNP's Web Valley. The combined effect of rabies and CDV increases the chance of pack extinction, exacerbating the typically slow recovery of wolf populations, and represents a key extinction threat to populations of this highly endangered carnivore. PMID:25898177

  19. European surveillance for pantropic canine coronavirus.

    Science.gov (United States)

    Decaro, Nicola; Cordonnier, Nathalie; Demeter, Zoltan; Egberink, Herman; Elia, Gabriella; Grellet, Aurélien; Le Poder, Sophie; Mari, Viviana; Martella, Vito; Ntafis, Vasileios; von Reitzenstein, Marcela; Rottier, Peter J; Rusvai, Miklos; Shields, Shelly; Xylouri, Eftychia; Xu, Zach; Buonavoglia, Canio

    2013-01-01

    Highly virulent pantropic canine coronavirus (CCoV) strains belonging to subtype IIa were recently identified in dogs. To assess the distribution of such strains in Europe, tissue samples were collected from 354 dogs that had died after displaying systemic disease in France (n = 92), Hungary (n = 75), Italy (n = 69), Greece (n = 87), The Netherlands (n = 27), Belgium (n = 4), and Bulgaria (n = 1). A total of 124 animals tested positive for CCoV, with 33 of them displaying the virus in extraintestinal tissues. Twenty-four CCoV strains (19.35% of the CCoV-positive dogs) detected in internal organs were characterized as subtype IIa and consequently assumed to be pantropic CCoVs. Sequence and phylogenetic analyses of the 5' end of the spike protein gene showed that pantropic CCoV strains are closely related to each other, with the exception of two divergent French viruses that clustered with enteric strains. PMID:23100349

  20. A canine model of multiple portosystemic shunting.

    Science.gov (United States)

    Howe, L M; Boothe, H W; Miller, M W; Boothe, D M

    2000-01-01

    The objective of this study was to develop and describe an experimental canine model of multiple acquired portosystemic shunts (PSS) similar in nature to spontaneously occurring PSS. Sixteen dogs were used and were divided into a control (n = 6) and a diseased group (n = 10). Dogs of the diseased group were administered dimethylnitrosamine (2 mg/kg of body weight, po) twice weekly, and clinicopathologic, ultrasonographic, and hepatic scintigraphic findings were recorded during the development of hepatic disease and PSS. Surgery was then performed to permit visual verification of multiple shunts, catheter placement for portography examination, and biopsy of the liver. All diseased dogs developed severe hepatic disease and multiple PSS as documented visually at surgery and on portography. Based on this study, dimethylnitrosamine-induced portosystemic shunting appears to be an appropriate model for spontaneously occurring multiple PSS secondary to portal hypertension. PMID:10741951

  1. Why segment the maxilla between laterals and canines?

    Directory of Open Access Journals (Sweden)

    Lucas Senhorinho Esteves

    2016-02-01

    Full Text Available Introduction: Maxillary surgery on a bone segment enables movement in the sagittal and vertical planes. When performed on multiple segments, it further provides movement in the transverse plane. Typical sites for interdental osteotomies are between laterals and canines, premolars and canines, or between incisors. Additionally, osteotomies can be bilateral, unilateral or asymmetric. The ability to control intercanine width, buccolingual angulation of incisors, and correct Bolton discrepancy are some of the advantages of maxillary segmentation between laterals and canines. Objective: This article describes important features to be considered in making a clinical decision to segment the maxilla between laterals and canines when treating a dentoskeletal deformity. It further discusses the history of this surgical approach, the indications for its clinical use, the technique used to implement it, as well as its advantages, disadvantages, complications and stability. It is therefore hoped that this paper will contribute to disseminate information on this topic, which will inform the decision-making process of those professionals who wish to make use of this procedure in their clinical practice. Conclusions: Segmental maxillary osteotomy between laterals and canines is a versatile technique with several indications. Furthermore, it offers a host of advantages compared with single-piece osteotomy, or between canines and premolars.

  2. Consequences of crown shortening canine teeth in Greenland sled dogs

    DEFF Research Database (Denmark)

    Kortegaard, H E; Anthony Knudsen, T; Dahl, S;

    2015-01-01

    OBJECTIVES: To evaluate the consequences of crown shortening, focusing on the prevalence of pulp exposure and periapical pathology in Greenland sled dogs that had had their canine crowns shortened at an early age. METHODS: Five cadaver heads and 54 sled dogs underwent an oral examination for dental...... fractures and pulp exposure of canines. All canines were radiographed and evaluated for periapical pathology. RESULTS: The prevalence of canine pulp exposure in 12 (5 heads and 7 dogs) crown shortened dogs was 91 · 7%, and 21 · 3% in 47 not-crown shortened dogs. A significant (P ... exposure of the canines in the crown shortened group compared to the not-crown shortened group was seen with a relative risk of 4 · 3 on a dog basis and a relative risk of 12 · 2 on a tooth basis. In dogs with pulp exposure of canines (n = 51) the prevalence of periapical pathology was 82 · 4%, but only 0...

  3. Chlamydia in canine or feline coronary arteriosclerotic lesions

    Directory of Open Access Journals (Sweden)

    Grabarevic Zeljko

    2011-09-01

    Full Text Available Abstract Background There are numerous reports linking Chlamydia infection to human coronary atherosclerosis. However, there is a lack of data regarding this correlation in dogs and cats, and there are no reports investigating coronary arteriosclerosis and Chlamydia in these species. The aim of the present study was to examine whether there is a correlation between canine and feline spontaneous atherosclerosis or arteriosclerosis and the presence of Chlamydia. Archived histopathological samples of dogs (n = 16 and cats (n = 13 with findings of atherosclerosis or arteriosclerosis in heart tissue were examined for the presence of Chlamydiaceae using real-time PCR, ArrayTube Microarray and immunohistochemistry. Additionally, arteriosclerotic lesions of all cases were histologically classified and graded. Results Both canine atherosclerotic cases, and all 14 canine arteriosclerotic cases were negative for Chlamydia. Only one of the 13 arteriosclerotic feline cases was positive for Chlamydia by real-time PCR, revealing C. abortus by ArrayTube Microarray. To our knowledge, this is the first description of C. abortus in a cat. Overall, the type and grade of canine and feline arteriosclerotic lesions revealed similarities, and were predominantly moderate and hyperplastic. Conclusions These findings suggest that there is no obvious correlation between canine and feline coronary arteriosclerosis and the presence of Chlamydia. In order to draw final conclusions about the correlation between Chlamydia and canine atherosclerosis, examination of more samples is required.

  4. Side Population Cells from Human Melanoma Tumors Reveal Diverse Mechanisms for Chemoresistance

    OpenAIRE

    Luo, Yuchun; Ellis, Lixia Z; Dallaglio, Katiuscia; Takeda, Moe; Robinson, William A.; Robinson, Steven; Liu, Weimin; Lewis, Karl D.; McCarter, Martin D; Gonzalez, Rene; David A Norris; Roop, Dennis R.; Spritz, Richard A.; Ahn, Natalie G.; Fujita, Mayumi

    2012-01-01

    Side population (SP) is identified as cells capable of excluding the fluorescent Hoechst dye and anticancer drugs, and represents hematopoietic stem cells and chemoresistant cells from several solid tumors. In this study, we confirmed the presence of SP cells in tumors from melanoma patients. Melanoma SP cells overexpressed ATP-binding-cassette (ABC) transporters, ABCB1 and ABCB5. We generated a direct in vivo xenograft model, and demonstrated that SP cells were resistant to paclitaxel, a sub...

  5. Overexpression of the anti-apoptotic protein AVEN contributes to increased malignancy in hematopoietic neoplasms.

    Science.gov (United States)

    Eißmann, M; Melzer, I M; Fernández, S B M; Michel, G; Hrabě de Angelis, M; Hoefler, G; Finkenwirth, P; Jauch, A; Schoell, B; Grez, M; Schmidt, M; Bartholomae, C C; Newrzela, S; Haetscher, N; Rieger, M A; Zachskorn, C; Mittelbronn, M; Zörnig, M

    2013-05-16

    AVEN has been identified as an inhibitor of apoptosis, which binds to the adaptor protein, APAF-1, and thereby prevents apoptosome formation and mitochondrial apoptosis. Recent data have demonstrated high expression levels of AVEN messenger RNA in acute leukemias as well as a positive correlation between AVEN mRNA overexpression and poor prognosis in childhood acute lymphoblastic leukemia. On the basis of these data, we investigated the potential involvement of AVEN in tumorigenesis. First, we confirmed the overexpression of AVEN in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) patient samples. We then established a transgenic mouse model with T-cell-specific overexpression of AVEN, with which we demonstrated the oncogenic cooperation of AVEN with heterozygous loss of p53. Finally, we used a subcutaneous xenograft mouse model to show that AVEN knockdown in the T-ALL cell lines, MOLT-4 and CCRF-CEM, and in the acute myeloblastic leukemia cell line, Kasumi-1, leads to a halt in tumor growth owing to the increased apoptosis and decreased proliferation of tumor cells. Collectively, our data demonstrate that the anti-apoptotic molecule, AVEN, functions as an oncoprotein in hematopoietic neoplasms. PMID:22751129

  6. Anti-Tumor Immunity in Head and Neck Cancer: Understanding the Evidence, How Tumors Escape and Immunotherapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Clint T. Allen

    2015-12-01

    Full Text Available Many carcinogen- and human papilloma virus (HPV-associated head and neck cancers (HNSCC display a hematopoietic cell infiltrate indicative of a T-cell inflamed phenotype and an underlying anti-tumor immune response. However, by definition, these tumors have escaped immune elimination and formed a clinically significant malignancy. A number of both genetic and environmental mechanisms may allow such immune escape, including selection of poorly antigenic cancer cell subsets, tumor produced proinflammatory and immunosuppressive cytokines, recruitment of immunosuppressive immune cell subsets into the tumor and expression of checkpoint pathway components that limit T-cell responses. Here, we explore concepts of antigenicity and immunogenicity in solid tumors, summarize the scientific and clinical data that supports the use of immunotherapeutic approaches in patients with head and neck cancer, and discuss immune-based treatment approaches currently in clinical trials.

  7. 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.

  8. Tumor necrosis factor receptor superfamily member 9 is upregulated in the endothelium and tumor cells in melanoma brain metastasis

    Directory of Open Access Journals (Sweden)

    Patrick N Harter

    2014-12-01

    Full Text Available Aim: The cytokine receptor tumor necrosis factor receptor superfamily member 9 (TNFRSF9 is mainly considered to be a co-stimulatory activation marker in hematopoietic cells. Several preclinical models have shown a dramatic beneficial effect of treatment approaches targeting TNFRSF9 with agonistic antibodies. However, preliminary clinical phase I/II studies were stopped after the occurrence of several severe deleterious side effects. In a previous study, it was demonstrated that TNFRSF9 was strongly expressed by reactive astrocytes in primary central nervous system (CNS tumors, but was largely absent from tumor or inflammatory cells. The aim of the present study was to address the cellular source of TNFRSF9 expression in the setting of human melanoma brain metastasis, a highly immunogenic tumor with a prominent tropism to the CNS. Methods: Melanoma brain metastasis was analyzed in a cohort of 78 patients by immunohistochemistry for TNFRSF9 and its expression was correlated with clinicopathological parameters including sex, age, survival, tumor size, number of tumor spots, and BRAF V600E expression status. Results: Tumor necrosis factor receptor superfamily member 9 was frequently expressed independently on both melanoma and endothelial cells. In addition, TNFRSF9 was also present on smooth muscle cells of larger vessels and on a subset of lymphomonocytic tumor infiltrates. No association between TNFRSF9 expression and patient survival or other clinicopathological parameters was seen. Of note, several cases showed a gradual increase in TNFRSF9 expression on tumor cells with increasing distance from blood vessels, an observation that might be linked to hypoxia-driven TNFRSF9 expression in tumor cells. Conclusion: The findings indicate that the cellular source of TNFRSF9 in melanoma brain metastasis largely exceeds the lymphomonocytic pool, and therefore further careful (re- assessment of potential TNFRSF9 functions in cell types other than

  9. Culture materials affect ex vivo expansion of hematopoietic progenitor cells.

    Science.gov (United States)

    LaIuppa, J A; McAdams, T A; Papoutsakis, E T; Miller, W M

    1997-09-01

    Ex vivo expansion of hematopoietic cells is important for applications such as cancer treatment, gene therapy, and transfusion medicine. While cell culture systems are widely used to evaluate the biocompatibility of materials for implantation, the ability of materials to support proliferation of primary human cells in cultures for reinfusion into patients has not been addressed. We screened a variety of commercially available polymer (15 types), metal (four types), and glass substrates for their ability to support expansion of hematopoietic cells when cultured under conditions that would be encountered in a clinical setting. Cultures of peripheral blood (PB) CD34+ cells and mononuclear cells (MNC) were evaluated for expansion of total cells and colony-forming unit-granulocyte monocyte (CFU-GM; progenitors committed to the granulocyte and/or monocyte lineage). Human hematopoietic cultures in serum-free medium were found to be extremely sensitive to the substrate material. The only materials tested that supported expansion at or near the levels of polystyrene were tissue culture polystyrene, Teflon perfluoroalkoxy, Teflon fluorinated ethylene propylene, cellulose acetate, titanium, new polycarbonate, and new polymethylpentene. MNC were less sensitive to the substrate materials than the primitive CD34+ progenitors, although similar trends were seen for expansion of the two cell populations on the substrates tested. CFU-GM expansion was more sensitive to substrate materials than was total cell expansion. The detrimental effects of a number of the materials on hematopoietic cultures appear to be caused by protein adsorption and/or leaching of toxins. Factors such as cleaning, sterilization, and reuse significantly affected the performance of some materials as culture substrates. We also used PB CD34+ cell cultures to examine the biocompatibility of gas-permeable cell culture and blood storage bags and several types of tubing commonly used with biomedical equipment

  10. Laser immunotherapy of canine and feline neoplasia

    Science.gov (United States)

    Woods, J. P.; Bartels, Kenneth E.; Davidson, Ellen B.; Ritchey, Jerry W.; Lehenbauer, Terry W.; Nordquist, Robert E.; Chen, Wei R.

    1998-07-01

    The major cause of treatment failure in human and veterinary cancer patients is tumor invasion and metastasis. The inability of local therapy (surgery, radiation, photodynamic therapy) to eradicate a metastatic cancer presents a challenge in the therapy of residual or micrometastatic disease. Because of its local therapy limitations, chromophore-enhanced selective photothermal laser treatment has been augmented with a superimposed laser-induced systemic photobiological reaction, laser immunotherapy. Laser immunotherapy is a novel cancer treatment consisting of: (1) a laser in the infrared wavelength range (i.e. 805 nm solid state laser); (2) a photosensitizer of the corresponding absorption peak [i.e. indocyanine green (ICG)]; and (3) an immunoadjuvant [i.e. glycated chitosan gel (GCG)]. The intratumor injection of the photosensitizer (ICG) and immunoadjuvant (GCG) solution is followed by noninvasive laser irradiation. The laser energy causes tumor cell destruction by photothermal interaction to reduce the tumor burden and at the same time exposes tumor antigens. The immunoadjuvant concomitantly stimulates the host to mount a systemic anti-tumor immune response against the remaining cells of the tumor and to induce a long-term, tumor-specific immunity. This study investigates the feasibility of utilizing laser immunotherapy as an adjunctive therapy for the control of feline fibrosarcoma in future.

  11. Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.

    Directory of Open Access Journals (Sweden)

    Kim M Boerkamp

    Full Text Available BACKGROUND: The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors have value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed. METHODS: Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS and disseminated, visceral histiocytic sarcomas (VHS and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR analyses. RESULTS: QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated, and GTSF1, Col3a1, CD90 and LUM (up-regulated in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process. CONCLUSIONS: This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Exploration of the downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human.

  12. Combination of radiation therapy and firocoxib for the treatment of canine nasal carcinoma.

    Science.gov (United States)

    Cancedda, Simona; Sabattini, Silvia; Bettini, Giuliano; Leone, Vito F; Laganga, Paola; Rossi, Federica; Terragni, Rossella; Gnudi, Giacomo; Vignoli, Massimo

    2015-01-01

    Carcinomas represent two-thirds of canine nasosinal neoplasms. Although radiation therapy (RT) is the standard of care, the incidence of local recurrence following treatment is high. Cyclooxygenase-isoform-2 (COX-2) is expressed in 71-95% of canine nasal carcinomas and has been implicated in tumor growth and angiogenesis. Accordingly, COX-2 inhibition seems rational to improve outcome. Dogs with histologically confirmed, previously untreated nasal carcinomas were randomized to receive the combination of a selective COX-2 inhibitor (firocoxib) and palliative RT (Group 1) or RT and placebo (Group 2). Patients were regularly monitored with blood tests, urinalysis, and computed tomography. Pet owners were asked to complete monthly a quality-of-life questionnaire. Twenty-four dogs were prospectively enrolled. According to Adams modified system, there were five stage 1, five stage 2, three stage 3, and 11 stage 4 tumors. Two dogs had metastases to regional lymph nodes. Median progression-free interval and overall survival were 228 and 335 days in Group 1 (n = 12) and 234 and 244 days in Group 2 (n = 12). These differences were not statistically significant. The involvement of regional lymph nodes was significantly associated with progression-free interval and overall survival (P = 0.004). Quality of life was significantly improved in Group 1 (P = 0.008). In particular, a significant difference was observed for activity and appetite. Although not providing a significant enhancement of progression-free interval and overall survival, firocoxib in combination with RT is safe and improved life quality in dogs with nasal carcinomas. PMID:25703137

  13. Rapid detection of radiation-induced chromosomal aberrations in lymphocytes and hematopoietic progenitor cells by mFISH

    Energy Technology Data Exchange (ETDEWEB)

    Greulich, K.M.; Rhein, A.P.; Brueckner, M.; Molls, M. [Department of Radiation Oncology, Technical University of Munich, Ismaninger Strasse 22, D-81675 Munich (Germany); Kreja, L. [Institute for Occupational, Social and Environmental Medicine, University of Ulm, Ulm (Germany); Heinze, B. [Department of Medical Genetics, University of Ulm, Ulm (Germany); Weier, H.-U.G. [Life Sciences Division, E.O. Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Fuchs, P. [Vysis GmbH, Bergisch-Gladbach (Germany)

    2000-07-20

    Structural chromosome aberrations (SCAs) are sensitive indicators of a preceding exposure of the hematopoietic system to ionizing radiation. Cytogenetic investigations have therefore become routine tools for an assessment of absorbed radiation doses and their biological effects after occupational exposure or radiation accidents. Due to its speed and ease of use, fluorescence in situ hybridization (FISH) with whole chromosome painting (WCP) probes has become a method of choice to visualize SCAs. Until recently, this technique was limited to a rather small number of chromosomes, which could be tested simultaneously. As a result, only a fraction of the structural aberrations present in a sample could be detected and the overall dose effect had to be calculated by extrapolation. The recent introduction of two genome-wide screening techniques in tumor research, i.e., Spectral Karyotyping (SKY) and multicolor FISH (mFISH) now allows the detection of translocations involving any two non-homologous chromosomes. The present study was prompted by our desire to bring the power of mFISH to bear for the rapid identification of radiation-induced SCAs. We chose two model systems to investigate the utility of mFISH: lymphocytes that were exposed in vitro to 3 Gy photons and single hematopoietic progenitor cell colonies isolated from a Chernobyl victim 9 years after in vivo exposure to 5.4 Sv. In lymphocytes, we found up to 15 different chromosomes involved in rearrangements indicating complex radiation effects. Stable aberrations detected in hematopoietic cell colonies, on the other hand, showed involvement of up to three different chromosomes. These results demonstrated that mFISH is a rapid and powerful approach to detect and characterize radiation-induced SCAs in the hemopoietic system. The application of mFISH is expected to result in a more detailed and, thus, more informative picture of radiation effects. Eventually, this technique will allow researchers to rapidly delineate

  14. A compendium of canine normal tissue gene expression.

    Directory of Open Access Journals (Sweden)

    Joseph Briggs

    Full Text Available BACKGROUND: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. METHODOLOGY/PRINCIPAL FINDINGS: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. CONCLUSIONS/SIGNIFICANCE: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

  15. Canine detection of free-ranging brown treesnakes on Guam

    Science.gov (United States)

    Savidge, J.A.; Stanford, J.W.; Reed, R.N.; Haddock, G.R.; Adams, A.A.Y.

    2011-01-01

    We investigated canine teams (dogs and their handlers) on Guam as a potential tool for finding invasive brown treesnakes (Boiga irregularis) in the wild. Canine teams searched a 40 ?? 40 m forested area for a snake that had consumed a dead mouse containing a radio-transmitter. To avoid tainting the target or target area with human scent, no snake was handled or closely approached prior to searches. Trials were conducted during the morning when these nocturnal snakes were usually hidden in refugia. A radiotracker knew the snake's location, but dog handlers and search navigators did not. Of 85 trials conducted over four months, the two canine teams had an average success rate of 35% of correctly defining an area ??? 5 ?? 5 m that contained the transmittered snake; the team with more experience prior to the trials had a success rate of 44% compared with 26% for the less experienced team. Canine teams also found 11 shed skins from wild snakes. Although dogs alerted outside the vicinity of transmittered snakes, only one wild, non-transmittered snake was found during the trials, possibly reflecting the difficulty humans have in locating non-transmittered brown treesnakes in refugia. We evaluated success at finding snakes as a function of canine team, number of prior trials (i.e. experience gained during the trials), recent canine success at finding a target snake, various environmental conditions, snake perch height, and snake characteristics (snout-vent length and sex). Success rate increased over the course of the trials. Canine team success also increased with increasing average humidity and decreased with increasing average wind speed. Our results suggest dogs could be useful at detecting brown treesnakes in refugia, particularly when compared to daytime visual searches by humans, but techniques are needed to help humans find and extract snakes once a dog has alerted. ?? New Zealand Ecological Society.

  16. A retrospective investigation of canine adenovirus (CAV) infection in adult dogs in Turkey : article

    OpenAIRE

    Gur, S; A. Acar

    2009-01-01

    Canine adenovirus (CAV) type 1 and 2, respectively, cause infectious canine hepatitis and infectious canine laryngotracheitis in members of the families Canidae and Ursidae worldwide. Both of these infections are acute diseases, especially in young dogs. The aim of this study was to conduct a serological investigation of canine adenovirus infection. For this purpose, serumsamples were collected from native pure-bred Kangal (n = 11), and Akbash dogs (n = 17) and Turkish Greyhounds (n=15) in Es...

  17. Aging, Clonality, and Rejuvenation of Hematopoietic Stem Cells.

    Science.gov (United States)

    Akunuru, Shailaja; Geiger, Hartmut

    2016-08-01

    Aging is associated with reduced organ function and increased disease incidence. Hematopoietic stem cell (HSC) aging driven by both cell intrinsic and extrinsic factors is linked to impaired HSC self-renewal and regeneration, aging-associated immune remodeling, and increased leukemia incidence. Compromised DNA damage responses and the increased production of reactive oxygen species (ROS) have been previously causatively attributed to HSC aging. However, recent paradigm-shifting concepts, such as global epigenetic and cytoskeletal polarity shifts, cellular senescence, as well as the clonal selection of HSCs upon aging, provide new insights into HSC aging mechanisms. Rejuvenating agents that can reprogram the epigenetic status of aged HSCs or senolytic drugs that selectively deplete senescent cells provide promising translational avenues for attenuating hematopoietic aging and, potentially, alleviating aging-associated immune remodeling and myeloid malignancies. PMID:27380967

  18. Erythropoietin guides multipotent hematopoietic progenitor cells toward an erythroid fate

    Science.gov (United States)

    Grover, Amit; Mancini, Elena; Moore, Susan; Mead, Adam J.; Atkinson, Deborah; Rasmussen, Kasper D.; O’Carroll, Donal; Jacobsen, Sten Eirik W.

    2014-01-01

    The erythroid stress cytokine erythropoietin (Epo) supports the development of committed erythroid progenitors, but its ability to act on upstream, multipotent cells remains to be established. We observe that high systemic levels of Epo reprogram the transcriptomes of multi- and bipotent hematopoietic stem/progenitor cells in vivo. This induces erythroid lineage bias at all lineage bifurcations known to exist between hematopoietic stem cells (HSCs) and committed erythroid progenitors, leading to increased erythroid and decreased myeloid HSC output. Epo, therefore, has a lineage instructive role in vivo, through suppression of non-erythroid fate options, demonstrating the ability of a cytokine to systematically bias successive lineage choices in favor of the generation of a specific cell type. PMID:24493804

  19. Regulation of stem cells in the zebra fish hematopoietic system.

    Science.gov (United States)

    Huang, H-T; Zon, L I

    2008-01-01

    Hematopoietic stem cells (HSCs) have been used extensively as a model for stem cell biology. Stem cells share the ability to self-renew and differentiate into multiple cell types, making them ideal candidates for tissue regeneration or replacement therapies. Current applications of stem cell technology are limited by our knowledge of the molecular mechanisms that control their proliferation and differentiation, and various model organisms have been used to fill these gaps. This chapter focuses on the contributions of the zebra fish model to our understanding of stem cell regulation within the hematopoietic system. Studies in zebra fish have been valuable for identifying new genetic and signaling factors that affect HSC formation and development with important implications for humans, and new advances in the zebra fish toolbox will allow other aspects of HSC behavior to be investigated as well, including migration, homing, and engraftment.

  20. Polycomb group proteins in hematopoietic stem cell aging and malignancies.

    Science.gov (United States)

    Klauke, Karin; de Haan, Gerald

    2011-07-01

    Protection of the transcriptional "stemness" network is important to maintain a healthy hematopoietic stem cells (HSCs) compartment during the lifetime of the organism. Recent evidence shows that fundamental changes in the epigenetic status of HSCs might be one of the driving forces behind many age-related HSC changes and might pave the way for HSC malignant transformation and subsequent leukemia development, the incidence of which increases exponentially with age. Polycomb group (PcG) proteins are key epigenetic regulators of HSC cellular fate decisions and are often found to be misregulated in human hematopoietic malignancies. In this review, we speculate that PcG proteins balance HSC aging against the risk of developing cancer, since a disturbance in PcG genes and proteins affects several important cellular processes such as cell fate decisions, senescence, apoptosis, and DNA damage repair.

  1. Haemopedia: An Expression Atlas of Murine Hematopoietic Cells

    Directory of Open Access Journals (Sweden)

    Carolyn A. de Graaf

    2016-09-01

    Full Text Available Hematopoiesis is a multistage process involving the differentiation of stem and progenitor cells into distinct mature cell lineages. Here we present Haemopedia, an atlas of murine gene-expression data containing 54 hematopoietic cell types, covering all the mature lineages in hematopoiesis. We include rare cell populations such as eosinophils, mast cells, basophils, and megakaryocytes, and a broad collection of progenitor and stem cells. We show that lineage branching and maturation during hematopoiesis can be reconstructed using the expression patterns of small sets of genes. We also have identified genes with enriched expression in each of the mature blood cell lineages, many of which show conserved lineage-enriched expression in human hematopoiesis. We have created an online web portal called Haemosphere to make analyses of Haemopedia and other blood cell transcriptional datasets easier. This resource provides simple tools to interrogate gene-expression-based relationships between hematopoietic cell types and genes of interest.

  2. Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency

    DEFF Research Database (Denmark)

    Qasim, Waseem; Cavazzana-Calvo, Marina; Davies, E Graham;

    2009-01-01

    of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International......, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases. CONCLUSIONS: Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early...... therapeutic option if a suitable HLA-matched stem-cell donation is available. Reduced-intensity conditioning was particularly safe, and mixed-donor chimerism seems sufficient to prevent significant symptoms, although careful long-term monitoring will be required for these patients....

  3. Lnk deficiency partially mitigates hematopoietic stem cell aging

    OpenAIRE

    Bersenev, Alexey; Rozenova, Krasimira; Balcerek, Joanna; JIANG, JING; Wu, Chao; Tong, Wei

    2012-01-01

    Upon aging, the number of hematopoietic stem cells (HSCs) in the bone marrow increases while their repopulation potential declines. Moreover, aged HSCs exhibit lineage bias in reconstitution experiments with an inclination towards myeloid at the expense of lymphoid potential. The adaptor protein Lnk is an important negative regulator of HSC homeostasis, as Lnk deficiency is associated with a 10-fold increase in HSC numbers in young mice. However, the age-related increase in functional HSC num...

  4. Massage for Children Undergoing Hematopoietic Cell Transplantation: A Qualitative Report

    OpenAIRE

    Ackerman, Sara L.; E. Anne Lown; Dvorak, Christopher C.; Dunn, Elizabeth A.; Abrams, Donald I; Horn, Biljana N.; Marcia Degelman; Cowan, Morton J.; Mehling, Wolf E.

    2012-01-01

    Background. No in-depth qualitative research exists about the effects of therapeutic massage with children hospitalized to undergo hematopoietic cell transplantation (HCT). The objective of this study is to describe parent caregivers' experience of the effects of massage/acupressure for their children undergoing HCT. Methods. We conducted a qualitative analysis of open-ended interviews with 15 parents of children in the intervention arm of a massage/acupressure trial. Children received both p...

  5. Hematopoietic Stem Cell Targeting with Surface-Engineered Lentiviral Vectors

    OpenAIRE

    sprotocols

    2014-01-01

    Authors: Els Verhoeyen and Francois-Loic Cosset Adapted from [*Gene Transfer: Delivery and Expression of DNA and RNA*](http://www.cshlpress.com/link/genetrnp.htm) (eds. Friedmann and Rossi). CSHL Press, Cold Spring Harbor, NY, USA, 2007. ### INTRODUCTION In the protocol presented here, hematopoietic stem cells (HSCs) are specifically transduced with a vector displaying the HSC-activating polypeptides, stem cell factor (SCF) and thrombopoietin (TPO). Targeted HSC transduction is e...

  6. Imaging of complications from hematopoietic stem cell transplant

    OpenAIRE

    Tarun Pandey; Suresh Maximin; Puneet Bhargava

    2014-01-01

    Stem cell transplant has been the focus of clinical research for a long time given its potential to treat several incurable diseases like hematological malignancies, diabetes mellitus, and neuro-degenerative disorders like Parkinson disease. Hematopoietic stem cell transplantation (HSCT) is the oldest and most widely used technique of stem cell transplant. HSCT has not only been used to treat hematological disorders including hematological malignancies, but has also been found useful in tream...

  7. Hematopoietic Stem and Immune Cells in Chronic HIV Infection

    OpenAIRE

    Jielin Zhang; Clyde Crumpacker

    2015-01-01

    Hematopoietic stem cell (HSC) belongs to multipotent adult somatic stem cells. A single HSC can reconstitute the entire blood system via self-renewal, differentiation into all lineages of blood cells, and replenishment of cells lost due to attrition or disease in a person's lifetime. Although all blood and immune cells derive from HSC, immune cells, specifically immune memory cells, have the properties of HSC on self-renewal and differentiation into lineage effector cells responding to the in...

  8. Radioprotection of hematopoietic progenitors by low dose amifostine prophylaxis

    OpenAIRE

    Seed, Thomas M.; Inal, Cynthia E.; Singh, Vijay K

    2014-01-01

    Purpose Amifostine is a highly efficacious cytoprotectant when administered in vivo at high doses. However, at elevated doses, drug toxicity manifests for general, non-clinical radioprotective purposes. Various strategies have been developed to avoid toxic side-effects: The simplest is reducing the dose. In terms of protecting hematopoietic tissues, where does this effective, non-toxic minimum dose lie? Material and methods C3H/HEN mice were administered varying doses of amifostine (25–100 mg...

  9. FIFTY YEARS OF MELPHALAN USE IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    OpenAIRE

    Bayraktar, Ulas D.; Bashir, Qaiser; Qazilbash, Muzaffar; Champlin, Richard E.; Ciurea, Stefan O.

    2012-01-01

    Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem-cell transplantation. From its initial discovery more than 50 years ago, it has been gradually incorporated in the conditioning regimens for both autologous and allogeneic transplantation due to its myeloablative properties and broad antitumor effects as a DNA alkylating agent. Melphalan remains the mainstay conditioning for multiple myeloma and lymphomas; and has been used successfully in preparative ...

  10. Regulation of Hematopoietic Stem Cells by Bone Marrow Stromal Cells

    OpenAIRE

    Anthony, Bryan; Link, Daniel C.

    2013-01-01

    Hematopoietic stem cells (HSCs) reside in specialized microenvironments (niches) in the bone marrow. The stem cell niche is thought to provide signals that support key HSC properties, including self-renewal capacity and long-term multilineage repopulation ability. The stromal cells that comprise the stem cell niche and the signals that they generate that support HSC function are the subjects of intense investigation. Here we review the complex and diverse stromal cell populations that reside ...

  11. Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

    OpenAIRE

    Ningning He; Lu Zhang; Jian Cui; Zongjin Li

    2014-01-01

    Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs). As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this rev...

  12. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ursula; M; Gehling; Marc; Willems; Kathleen; Schlagner; Ralf; A; Benndorf; Maura; Dandri; Jrg; Petersen; Martina; Sterneck; Joerg-Matthias; Pollok; Dieter; K; Hossfeld; Xavier; Rogiers

    2010-01-01

    AIM:To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS:Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry.Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1(SDF-1) were measured using an enzyme linked immunosorbent assay.RESULTS:Progenitor cells with a CD133 + /CD45 + CD14 + phenotype we...

  13. Bcl11b mutations identified in murine lymphomas increase the proliferation rate of hematopoietic progenitor cells

    Directory of Open Access Journals (Sweden)

    Söderkvist Peter

    2007-10-01

    Full Text Available Abstract Background The telomeric region of mouse chromosome 12 has previously shown frequent allelic loss in murine lymphoma. The Bcl11b gene has been identified and suggested as a candidate tumor suppressor gene within this region. In this study, we aimed to elucidate whether Bcl11b is mutated in lymphomas with allelic loss, and whether the mutations we detected conferred any effect on cell proliferation and apoptosis. Methods Mouse lymphomas induced by 1,3-butadiene or 2',3'-dideoxycytidine were analysed for mutations in the Bcl11b gene using single strand conformation analysis and direct DNA sequencing. Effects on cell proliferation by the detected mutations were studied by expressing wild-type and mutant Bcl11b in the cytokine-dependent hematopoietic progenitor cell line FDC-P1, lacking endogenous Bcl11b expression. Results Missense and frameshift (FS mutations were identified in 7 of 47 tumors (15%. Interestingly, all mutations were found between amino acids 778–844 which encode the three C-terminal DNA-binding zinc fingers. In FDC-P1 cells, wild-type Bcl11b suppressed cell proliferation, whereas the mutated versions (S778N, K828T, Y844C and FS823 enhanced proliferation several-fold. Conclusion The genetic alterations detected in this study suggest that the three C-terminal zinc fingers of Bcl11b are important for the DNA-binding. Cell proliferation was suppressed by overexpression of wild-type Bcl11b but enhanced by mutant Bcl11b, indicating that these mutations may be an important contributing factor to lymphomagenesis in a subset of tumors.

  14. Accuracy of Trained Canines for Detecting Bed Bugs (Hemiptera: Cimicidae).

    Science.gov (United States)

    Cooper, Richard; Wang, Changlu; Singh, Narinderpal

    2014-12-01

    Detection of low-level bed bug, Cimex lectularius L. (Hemiptera: Cimicidae), infestations is essential for early intervention, confirming eradication of infestations, and reducing the spread of bed bugs. Despite the importance of detection, few effective tools and methods exist for detecting low numbers of bed bugs. Scent dogs were developed as a tool for detecting bed bugs in recent years. However, there are no data demonstrating the reliability of trained canines under natural field conditions. We evaluated the accuracy of 11 canine detection teams in naturally infested apartments. All handlers believed their dogs could detect infestations at a very high rate (≥95%). In three separate experiments, the mean (min, max) detection rate was 44 (10-100)% and mean false-positive rate was 15 (0-57)%. The false-positive rate was positively correlated with the detection rate. The probability of a bed bug infestation being detected by trained canines was not associated with the level of bed bug infestations. Four canine detection teams evaluated on multiple days were inconsistent in their ability to detect bed bugs and exhibited significant variance in accuracy of detection between inspections on different days. There was no significant relationship between the team's experience or certification status of teams and the detection rates. These data suggest that more research is needed to understand factors affecting the accuracy of canine teams for bed bug detection in naturally infested apartments. PMID:26470083

  15. Understanding the radiosensitivity of hematopoietic stem cells through CDNA micro-arrays profiling

    Energy Technology Data Exchange (ETDEWEB)

    Pawlik, A.; Cebo, Ch.; Vaigot, P.; Tronik-Le Roux, D. [Evry Univ., Lab. de Genomique et Radiobiologie de l' Hematopoiese, Service de Genomique Fonctionnelle, CEA, 91 (France)

    2006-07-01

    Eradication of circulating hematopoietic cells has been long known to be the first noticeable somatic effect following total body ionizing radiation (IR) exposure. Among these hematopoietic cells a marked differences in sensitivity to IR have been documented reflecting the remarkable degree of heterogeneity in cell type, proliferative capacity and cell cycle status within the bone marrow cells. From all the hematopoietic cells, the small lymphocyte has the greatest radiosensitivity. In fact, a decline in absolute lymphocyte count has been used to assess IR dose in the early phase of observation after IR exposure. At moderate doses, bone marrow recovery is triggered by the differentiation of stem/early progenitor cells, which confirms further their differential sensitivity to radiation exposure. Although differences in radiosensitivity of the stem cell pool have also been documented, little is known from a molecular viewpoint. To gain insight into the molecular programs underlying the response o f hematopoietic cells to radiation exposure, we have applied a genome wide analysis strategy based on cDNA micro arrays. This technology offers a unique opportunity to dissect complex biological process by assessing three types of questions, which are, in order of complexity: Which genes are differentially expressed among the samples studied:Which genes are expressed in a coordinated manner and what are the regulators involved,what are the global biological pathways mobilized. To answer these questions transcriptional changes occurring after exposure of mice to whole body irradiation (2 Gy) were monitored in bone marrow and spleen. The time course was established in vivo and encompassed the reversible eradication of cells. For each kinetic point RNA was collected from both, spleen or sorted B.M. populations from irradiated and sham irradiated mice. The sham irradiated mice were used to eliminate stress modifications due to handling.The results highlight numerous

  16. The in vivo study of myeloprotection by GST-π gene transfected human cord blood hematopoietic stem cells transplantation

    Institute of Scientific and Technical Information of China (English)

    Yang Xingsheng; Yu Chenghao; Kong Yawei; Jiang Jie; Dong Ruiying; Cui Baoxia; Wang Lijie; Jiang Sen

    2003-01-01

    Objective:To investigate the influence of GST-π gene transfer into human cord blood hematopoietic stem cells on their drug resistance against anti-tumor drugs in vivo.Methods:GST-π gene transfection into human cord blood CD34+ cells was carried out using a retrovirus vector PLJ-GST-π with the aid of fibronectin.Successful gene transfer was confirmed by in vitro colony assay and RT-PCR.GST-π gene transduced human cord blood CD34+ cells were then engrafted into 4-week-old total body irradiated NOD/Scid mice and carboplatin was intraperitoneally administered sequentially at 4 weeks interval 4 weeks after engraftment.Results:Peripheral blood(PB) WBC was significantly higher in GST-π mice than control mice after 2 course of carboplatin.Retroviral GST-π expression in bone marrow hematopoietic progenitor cells of recipient mice was detected by RT-PCR 16 weeks after Xenotransplantation.Conclusion:The transfection of GST-π gene could confer,to some extent,resistance to cord blood stem cells against carboplatin in vivo.

  17. Designer blood: creating hematopoietic lineages from embryonic stem cells

    Science.gov (United States)

    Olsen, Abby L.; Stachura, David L.; Weiss, Mitchell J.

    2006-01-01

    Embryonic stem (ES) cells exhibit the remarkable capacity to become virtually any differentiated tissue upon appropriate manipulation in culture, a property that has been beneficial for studies of hematopoiesis. Until recently, the majority of this work used murine ES cells for basic research to elucidate fundamental properties of blood-cell development and establish methods to derive specific mature lineages. Now, the advent of human ES cells sets the stage for more applied pursuits to generate transplantable cells for treating blood disorders. Current efforts are directed toward adapting in vitro hematopoietic differentiation methods developed for murine ES cells to human lines, identifying the key interspecies differences in biologic properties of ES cells, and generating ES cell-derived hematopoietic stem cells that are competent to repopulate adult hosts. The ultimate medical goal is to create patient-specific and generic ES cell lines that can be expanded in vitro, genetically altered, and differentiated into cell types that can be used to treat hematopoietic diseases. PMID:16254136

  18. Experiments on Gene Transferring to Primary Hematopoietic Cells by Liposome

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Liposomes have showed many advantages in mediating exogenous gene into many cell types in vitro and in vivo. But few data are available concerning gene transfer into hematopoietic cells. In this report, we described two-marker genes (Neo R and Lac Z) co-transferred into hematopoietic cells of human and mouse by using liposome in vitro. The efficiency of gene transfer was tested by Xgal staining and observation of colony formation. The X-gal blue staining rate of transduced cells was about (13.33±2. 68) % in human and about (16. 28±2.95) % in mouse without G418 selection. After G418 selection, the blue cell rate was (46. 06±3.47)%in human and (43. 45±4. 1) % in mouse, which were markedly higher than those before selection, suggesting that high-efficiency gene transfer and expression could be attained in primary hematopoietic cells using this easy and harmless transduction protocol. At the same time, this protocol provided experimental data for clinicians to investigate the biology of marrow reconstitution and trace the origin of relapse after autologous bone marrow transplantation for the patients with leukemia.

  19. Hematopoietic Stem Cells Expansion in Rotating Wall Vessel

    Institute of Scientific and Technical Information of China (English)

    Yang LIU; Tian-Qing LIU; Xiu-Bo FAN; Dan GE; Zhan-Feng CUI; Xue-Hu MA

    2005-01-01

    @@ 1 Introduction Clinical trials have demonstrated that ex vivo expanded hematopoietic stem cells (HSCs) and progenitors offer great promise in reconstituting in vivo hematopoiesis in patients who have undergone intensive chemotherapy.It is therefore necessary to develop a clinical-scale culture system to provide the expanded HSCs and progenitors.Static culture systems such as T-flasks and gas-permeable blood bags are the most widely used culture devices for expanding hematopoietic cells. But they reveal several inherent limitations: ineffective mixing, lack of control options for dissolved oxygen and pH and difficulty in continuous feeding, which restricts the usefulness of static systems. Several advanced bioreactors have been used in the field of HSCs expansion. But hematopoietic cells are extremely sensitive to shear, so cells in bioreactors such as stirred and perfusion culture systems may suffer physical damage. This problem will be improved by applying the rotating wall vessel (RWV) bioreactor in clinic because of its low shear and unique structure. In this research, cord blood (CB) HSCs were expanded by means of a cell-dilution feeding protocol in RWV.

  20. Bone Marrow GvHD after Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Szyska, Martin; Na, Il-Kang

    2016-01-01

    The bone marrow is the origin of all hematopoietic lineages and an important homing site for memory cells of the adaptive immune system. It has recently emerged as a graft-versus-host disease (GvHD) target organ after allogeneic stem cell transplantation (alloHSCT), marked by depletion of both hematopoietic progenitors and niche-forming cells. Serious effects on the restoration of hematopoietic function and immunological memory are common, especially in patients after myeloablative conditioni...

  1. Involvement of primary mesenchymal precursors and hematopoietic bone marrow cells from chronic myeloid leukemia patients by BCR-ABL1 fusion gene.

    Science.gov (United States)

    Chandia, Mauricio; Sayagués, José-María; Gutiérrez, María-Laura; Chillón, María-Laura; Aristizábal, José-Alejandro; Corrales, Alejandro; Castellanos, Marta; Melón, Alberto; Sánchez, María-Luz; Bárcena, Paloma; Matarraz, Sergio; González-González, María; Barrena, Susana; López, Antonio; Cañizo, María-Consuelo; Sánchez-Guijo, Fermín; Orfao, Alberto

    2014-03-01

    For decades now, it is well established that chronic myeloid leukemia (CML) is a hematopoietic stem cell(HPC) disorder. However, it remains to be determined whether BCR-ABL1 gene rearrangement occurs in a HPC or at an earlier stem cell and whether the degree of involvement of hematopoiesis by the BCR-ABL1 fusion gene relates to the response to therapy. Here, we have investigated by interphase fluorescence in situ hybridization (iFISH) the distribution of BCR-ABL1 fusion gene in FACS-sorted bone marrow (BM) populations of mesenchymal precursor cells (MPC) and other hematopoietic cell populations from 18 newly diagnosed CML patients. Overall, our results showed systematic involvement at relatively high percentages of BM maturing neutrophils (97%615%), basophils (95%612%), eosinophils (90%68%), CD341 precursors cells (90%67%),monocytes (84%630%), nucleated red blood cells (87%624%), and mast cells (77%633%). By contrast, MPC(30%634%), B-cells (15%627%), T-lymphocytes (50%626%), and NK-cells (35%634%) were involved at lower percentages. In 8/18 CML patients, 2 tumor BCR-ABL11 subclones were detected by iFISH. Of note, all tumor cell subclones were systematically detected in CD341 cells, whereas MPC were only involved by the ancestral tumor cell subclone. In summary, here we confirm the presence at diagnosis of the BCR-ABL1 fusion gene inMPC, CD341 precursors, and other different BM hematopoietic myeloid cell lineages from CML patients,including also in a significant fraction of cases, a smaller percentage of T, B, and NK lymphocytes.Interestingly, involvement of MPC was restricted to the ancestral BCR-ABL11 subclone. PMID:24779036

  2. 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

  3. Effect of simulated stages of the canine oestrous cycle on Escherichia coli binding to canine endometrium.

    Science.gov (United States)

    Krekeler, N; Lodge, K M; Anderson, G A; Browning, G F; Charles, J A; Wright, P J

    2012-12-01

    Pyometra, a prevalent infectious uterine disease that affects intact middle-aged bitches, is typically associated with Escherichia coli. Our hypotheses were (i) that bacterial adhesion to canine endometrium differs between different stages of the oestrous cycle and (ii) that the adhesin FimH facilitates this adhesion. Twelve post-pubertal, ovariectomized greyhound bitches were treated with exogenous hormones to simulate different stages of the oestrous cycle. Tissue samples from each uterus were incubated with a pathogenic E. coli strain carrying the fimH gene, but no other adhesin genes (P4-wt)--or an E. coli strain in which fimH was insertionally inactivated (P4-∆fimH::kan)--or with phosphate-buffered saline as a negative control. After washing, tissue samples were homogenized for quantification of adherent bacteria. The differences in binding to canine endometrium at different stages of the oestrous cycle were not significant. However, the mean difference in binding of the P4-wt and the P4-∆fimH::kan across all stages of the simulated oestrous cycle was significant (p dogs might suggest genetic variations or epigenetic differences in FimH receptor expression by the endometrium, unrelated to the stage of the oestrous cycle. PMID:23279531

  4. Effects of the canine rattlesnake vaccine in moderate to severe cases of canine crotalid envenomation

    Directory of Open Access Journals (Sweden)

    Leonard MJ

    2014-10-01

    Full Text Available McGee J Leonard,1 Catherine Bresee,2 Andrew Cruikshank1 1Animal Specialty and Emergency Center, Los Angeles, CA, USA; 2The Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: This is a retrospective multicenter study (2006–2012 examining a population of dogs with moderate to severe crotalid envenomation for protective effects of the canine rattlesnake vaccine. Five nonacademic emergency and referral veterinary hospitals in Southern California were involved in the study and contributed records regarding a total of 82 client-owned dogs that were treated for naturally occurring rattlesnake envenomation. All dogs received antivenin (Crotalidae polyvalent, with dosages ranging from one to three vials (mean: 1.3±0.6. Fourteen dogs (17% had a history of prior vaccination against crotalid venom. In univariate logistic regression modeling, cases with lower body weight (P=0.0001 or higher snakebite severity scores (P<0.0001 were associated with greater morbidity. No statistically significant difference in morbidity or mortality between vaccinated and unvaccinated dogs was found. The findings of this study did not identify a significantly protective effect of previous vaccination in the cases of moderate to severe rattlesnake envenomation that require treatment with antivenin. Keywords: rattlesnake envenomation, vaccine, antivenin, canine

  5. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin.

    Science.gov (United States)

    Palchaudhuri, Rahul; Saez, Borja; Hoggatt, Jonathan; Schajnovitz, Amir; Sykes, David B; Tate, Tiffany A; Czechowicz, Agnieszka; Kfoury, Youmna; Ruchika, Fnu; Rossi, Derrick J; Verdine, Gregory L; Mansour, Michael K; Scadden, David T

    2016-07-01

    Hematopoietic stem cell transplantation (HSCT) offers curative therapy for patients with hemoglobinopathies, congenital immunodeficiencies, and other conditions, possibly including AIDS. Autologous HSCT using genetically corrected cells would avoid the risk of graft-versus-host disease (GVHD), but the genotoxicity of conditioning remains a substantial barrier to the development of this approach. Here we report an internalizing immunotoxin targeting the hematopoietic-cell-restricted CD45 receptor that effectively conditions immunocompetent mice. A single dose of the immunotoxin, CD45-saporin (SAP), enabled efficient (>90%) engraftment of donor cells and full correction of a sickle-cell anemia model. In contrast to irradiation, CD45-SAP completely avoided neutropenia and anemia, spared bone marrow and thymic niches, enabling rapid recovery of T and B cells, preserved anti-fungal immunity, and had minimal overall toxicity. This non-genotoxic conditioning method may provide an attractive alternative to current conditioning regimens for HSCT in the treatment of non-malignant blood diseases. PMID:27272386

  6. [Diagnostic tools for canine parvovirus infection].

    Science.gov (United States)

    Proksch, A L; Hartmann, K

    2015-01-01

    Canine parvovirus (CPV) infection is one of the most important and common infectious diseases in dogs, in particular affecting young puppies when maternal antibodies have waned and vaccine-induced antibodies have not yet developed. The mortality rate remains high. Therefore, a rapid and safe diagnostic tool is essential to diagnose the disease to 1) provide intensive care treatment and 2) to identify virus-shedding animals and thus prevent virus spread. Whilst the detection of antibodies against CPV is considered unsuitable to diagnose the disease, there are several different methods to directly detect complete virus, virus antigen or DNA. Additionally, to test in commercial laboratories, rapid in-house tests based on ELISA are available worldwide. The specificity of the ELISA rapid in-house tests is reported to be excellent. However, results on sensitivity vary and high numbers of false-negative results are commonly reported, which potentially leads to misdiagnosis. Polymerase chain reaction (PCR) is a very sensitive and specific diagnostic tool. It also provides the opportunity to differentiate vaccine strains from natural infection when sequencing is performed after PCR.

  7. Haematological and biochemical analysis in canine enteritis

    Directory of Open Access Journals (Sweden)

    Abid Ali Bhat

    Full Text Available Aim: The present investigation screened eighteen clinical cases of canine enteritis for haematological and biochemical analyses. Materials and Methods: Eighteen dogs suffering from enteritis were selected and detailed clinical manifestations were noted. Hematological and biochemical parameters were estimated by using various kits. Blood was also collected from twelve healthy dogs for establishing control values and data obtained were subjected to statistical analysis. Results: The affected dogs showed anorexia, diarrhoea, depression, varying degree of dehydration and tachycardia. There were significant changes in packed cell volume, neutrophils, lymphocytes and mean corpuscular haemoglobin concentration. Biochemical investigation revealed significant decrease in plasma glucose, total plasma protein, albumin and albumin:globulin ratio (A:G ratio. The level of potassium and chloride was markedly decreased. Significant increase in alanine aminotransferase (ALT and blood urea nitrogen (BUN was observed. Conclusion: Packed Cell Volume (PCV and Total Erythrocyte Count (TEC remained almost similar between healthy dogs and dogs affected with diarrhoea. Mean Total Leukocyte Count (TLC value was significantly higher as compared to the control group. Hypoglycemia, hypoproteinemia, hypokalemia, hypochloremia and increase in blood urea nitrogen was observed in dogs suffering from enteritis. [Vet World 2013; 6(7.000: 380-383

  8. Canine detection odor signatures for explosives

    Science.gov (United States)

    Williams, Marc; Johnston, J. M.; Cicoria, Matt; Paletz, E.; Waggoner, L. Paul; Edge, Cindy C.; Hallowell, Susan F.

    1998-12-01

    Dogs are capable of detecting and discriminating a number of compounds constituting a complex odor. However, they use only a few of these to recognize a substance. The focus of this research is to determine the compounds dogs learn to use in recognizing explosives. This is accomplished by training dogs under behavioral laboratory conditions to respond differentially on separate levers to 1) blank air, 2) a target odor, such as an explosive, and 3) all other odors (non-target odors). Vapor samples are generated by a serial dilution vapor generator whose operation and output is characterized by GC/MS. Once dogs learn this three-lever discrimination, testing sessions are conducted containing a number of probe trials in which vapor from constituent compounds of the target is presented. Which lever the dogs respond to on these probe trials indicates whether they can smell the compound at all (blank lever) or whether it smells like toe target odor (e.g., the explosive) or like something else. This method was conducted using TNT, C-4, and commercial dynamite. The data show the dogs' reactions to each of the constituent compounds tested for each explosive. Analysis of these data reveal the canine detection odor signature for these explosives.

  9. TET2 deficiency inhibits mesoderm and hematopoietic differentiation in human embryonic stem cells

    DEFF Research Database (Denmark)

    Langlois, Thierry; da Costa Reis Monte Mor, Barbara; Lenglet, Gaëlle;

    2014-01-01

    . Here, we show that TET2 expression is low in human embryonic stem (ES) cell lines and increases during hematopoietic differentiation. ShRNA-mediated TET2 knockdown had no effect on the pluripotency of various ES cells. However, it skewed their differentiation into neuroectoderm at the expense...... profile, including abnormal expression of neuronal genes. Intriguingly, when TET2 was knockdown in hematopoietic cells, it increased hematopoietic development. In conclusion, our work suggests that TET2 is involved in different stages of human embryonic development, including induction of the mesoderm...... and hematopoietic differentiation. Stem Cells 2014....

  10. Chromosomal assignment of canine THADA gene to CFA 10q25

    Directory of Open Access Journals (Sweden)

    Dolf Gaudenz

    2008-06-01

    Full Text Available Abstract Background Chromosomal translocations affecting the chromosome 2p21 cluster in a 450 kb breakpoint region are frequently observed in human benign thyroid adenomas. THADA (thyroid adenoma associated was identified as the affected gene within this breakpoint region. In contrast to man tumours of the thyroid gland of dogs (Canis lupus familiaris constitute mainly as follicular cell carcinomas, with malignant thyroid tumours being more frequent than benign thyroid adenomas. In order to elucidate if the THADA gene is also a target of chromosomal rearrangements in thyroid adenomas of the dog we have physically mapped the canine THADA gene to canine chromosome 10. A PCR was established to screen a canine genome library for a BAC clone containing the gene sequence of canine THADA. Further PCR reactions were done using the identified BAC clone as a template in order to verify the corresponding PCR product by sequencing. Canine whole blood was incubated with colcemid in order to arrest the cultured cells in metaphases. The verified BAC DNA was digoxigenin labeled and used as a probe in fluorescence in situ hybridization (FISH. Ten well spread metaphases were examined indicating a signal on canine chromosome 10 on both chromatids. A detailed fine mapping was performed indicating the canine THADA gene locus on the q-arm of chromosome 10. Results The canine THADA gene locus was mapped on chromosome 10q25. Our mapping results obtained in this study following the previously described nomenclature for the canine karyotype. Conclusion We analysed whether the THADA gene locus is a hotspot of canine chromosomal rearrangements in canine neoplastic lesions of the thyroid and in addition might play a role as a candidate gene for a possible malignant transformation of canine thyroid adenomas. Although the available cytogenetic data of canine thyroid adenomas are still insufficient the chromosomal region to which the canine THADA has been mapped seems to be no

  11. Finite element analysis of rapid canine retraction through reducing resistance and distraction

    Directory of Open Access Journals (Sweden)

    Junjie XUE

    2014-01-01

    Full Text Available Objective: The aims of this study were to compare different surgical approaches to rapid canine retraction by designing and selecting the most effective method of reducing resistance by a three-dimensional finite element analysis. Material and Methods: Three-dimensional finite element models of different approaches to rapid canine retraction by reducing resistance and distraction were established, including maxillary teeth, periodontal ligament, and alveolar. The models were designed to dissect the periodontal ligament, root, and alveolar separately. A 1.5 N force vector was loaded bilaterally to the center of the crown between first molar and canine, to retract the canine distally. The value of total deformation was used to assess the initial displacement of the canine and molar at the beginning of force loading. Stress intensity and force distribution were analyzed and evaluated by Ansys 13.0 through comparison of equivalent (von Mises stress and maximum shear stress. Results: The maximum value of total deformation with the three kinds of models occurred in the distal part of the canine crown and gradually reduced from the crown to the apex of the canine; compared with the canines in model 3 and model 1, the canine in model 2 had the maximum value of displacement, up to 1.9812 mm. The lowest equivalent (von Mises stress and the lowest maximum shear stress were concentrated mainly on the distal side of the canine root in model 2. The distribution of equivalent (von Mises stress and maximum shear stress on the PDL of the canine in the three models was highly concentrated on the distal edge of the canine cervix. . Conclusions: Removal of the bone in the pathway of canine retraction results in low stress intensity for canine movement. Periodontal distraction aided by surgical undermining of the interseptal bone would reduce resistance and effectively accelerate the speed of canine retraction.

  12. FDG PET/CT in Acute Tumefactive Multiple Sclerosis Occurring in a Case of Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Dong, Aisheng; Gao, Mingjun; Wang, Yang; Gao, Lei; Zuo, Changjing

    2016-09-01

    Tumefactive multiple sclerosis refers to the presentation of large demyelinating lesions (≥2 cm in diameter) mimicking brain tumors clinically and radiologically. We present the MRI and FDG PET/CT findings in a case with tumefactive multiple sclerosis, who had chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Head MRI showed 7 cerebral lesions with incomplete ring enhancement. All but one lesion had size more than 2 cm. All these demyelinating lesions showed increased uptake at the rims of the lesions with central hypometabolism. Stereotactic brain biopsy of the right frontal lesion revealed extensive macrophage and lymphocyte infiltration. PMID:26909714

  13. Cryopreservation of hematopoietic stem/progenitor cells for therapeutic use.

    Science.gov (United States)

    Watt, Suzanne M; Austin, Eric; Armitage, Sue

    2007-01-01

    To date, more than 25,000 hematopoietic transplants have been carried out across Europe for hematological disorders, the majority being for hematological malignancies. At least 70% of these are autologous transplants, the remaining 30% being allogeneic, which are sourced from related (70% of the allogeneic) or unrelated donors. Peripheral blood mobilized with granulocyte colony stimulating factor is the major source of stem cells for transplantation, being used in approx 95% of autologous transplants and in approx 65% of allogeneic transplants. Other cell sources used for transplantation are bone marrow and umbilical cord blood. One crucial advance in the treatment of these disorders has been the development of the ability to cryopreserve hematopoietic stem cells for future transplantation. For bone marrow and mobilized peripheral blood, the majority of cryopreserved harvests come from autologous collections that are stored prior to a planned infusion following further treatment of the patient or at the time of a subsequent relapse. Other autologous harvests are stored as backup or "rainy day" harvests, the former specifically being intended to rescue patients who develop graft failure following an allogeneic transplant or who may require this transplant at a later date. Allogeneic bone marrow and mobilized peripheral blood are less often cryopreserved than autologous harvests. This is in contrast to umbilical cord blood that may be banked for directed or sibling (related) hematopoietic stem cell transplants, for allogeneic unrelated donations, and for autologous donations. Allogeneic unrelated donations are of particular use for providing a source of hematopoietic stem cells for ethnic minorities, patients with rare human leukocyte antigen types, or where the patient urgently requires a transplant and cannot wait for the weeks to months required to prepare a bone marrow donor. There are currently more than 200,000 banked umbilical cord blood units registered with

  14. Immunopathogenic and Neurological Mechanisms of Canine Distemper Virus

    Directory of Open Access Journals (Sweden)

    Otávio Valério Carvalho

    2012-01-01

    Full Text Available Canine distemper is a highly contagious viral disease caused by the canine distemper virus (CDV, which is a member of the Morbillivirus genus, Paramyxoviridae family. Animals that most commonly suffer from this disease belong to the Canidae family; however, the spectrum of natural hosts for CDV also includes several other families of the order Carnivora. The infectious disease presents worldwide distribution and maintains a high incidence and high levels of lethality, despite the availability of effective vaccines, and no specific treatment. CDV infection in dogs is characterized by the presentation of systemic and/or neurological courses, and viral persistence in some organs, including the central nervous system (CNS and lymphoid tissues. An elucidation of the pathogenic mechanisms involved in canine distemper disease will lead to a better understanding of the injuries and clinical manifestations caused by CDV. Ultimately, further insight about this disease will enable the improvement of diagnostic methods as well as therapeutic studies.

  15. Feline and Canine Coronaviruses: Common Genetic and Pathobiological Features

    Directory of Open Access Journals (Sweden)

    Sophie Le Poder

    2011-01-01

    Full Text Available A new human coronavirus responsible for severe acute respiratory syndrome (SARS was identified in 2003, which raised concern about coronaviruses as agents of serious infectious disease. Nevertheless, coronaviruses have been known for about 50 years to be major agents of respiratory, enteric, or systemic infections of domestic and companion animals. Feline and canine coronaviruses are widespread among dog and cat populations, sometimes leading to the fatal diseases known as feline infectious peritonitis (FIP and pantropic canine coronavirus infection in cats and dogs, respectively. In this paper, different aspects of the genetics, host cell tropism, and pathogenesis of the feline and canine coronaviruses (FCoV and CCoV will be discussed, with a view to illustrating how study of FCoVs and CCoVs can improve our general understanding of the pathobiology of coronaviruses.

  16. Canine dysautonomia in a litter of Havanese puppies.

    Science.gov (United States)

    Hull, Noah C; O'Toole, Donal; Miller, Myrna M; Shoults, Hannah; Deck, Robin; Jones, Warren; Johnson, Gayle C; Shaw, Daniel P; Schumaker, Brant A

    2015-09-01

    Canine dysautonomia is a sporadic, generally fatal disease that rarely affects groups of related animals. Four 10-week-old Havanese puppies from a litter of 5 developed clinical signs of canine dysautonomia. The 4 affected dogs were exposed to an outdoor environment, whereas the fifth littermate was not exposed to the outdoors and remained clinically healthy. Clinical signs of dysautonomia developed 10-16 days after going outside the house. An unrelated dog also developed dysautonomia after exposure to 1 of the affected Havanese littermates. All 5 dogs had morphological changes consistent with dysautonomia (widespread neuronal degeneration in autonomic ganglia, select brainstem nuclei, and ventral horn motor neurons). Differential diagnoses were excluded through negative toxicological evaluation, fecal parasite screening, negative Canine distemper virus reverse transcription polymerase chain reaction, fluorescent antibody testing, attempted virus isolation, and electron microscopy. The 5 affected dogs were in the Kansas City, Missouri area, where there is a high incidence of dysautonomia. PMID:26179098

  17. Testosterone biotransformation by the isolated perfused canine pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-del Castillo, C.; Diaz-Sanchez, V.; Varela-Fascinetto, G.; Altamirano, A.; Odor-Morales, A.; Lopez-Medrano, R.M.; Robles-Diaz, G. (Instituto Nacional de la Nutricion Salvador Zubiran, Mexico City (Mexico))

    1991-01-01

    There is strong evidence indicating that the pancreas is under the influence of sex steroid hormones, and that it may even participate in their biosynthesis and metabolism. In the present study, (3H)testosterone was perfused into the isolated canine pancreas, and measured in the effluent with several of its metabolites (5 alpha-dihydrotestosterone, androstenedione, and estradiol). Results show that testosterone is readily transformed by the canine pancreas. The main product found in the effluent is androstenedione. The testis and spleen were also perfused with (3H)testosterone and used as controls. In both cases, this hormone appeared mostly unchanged in the effluent as compared to the pancreatic perfusion (p less than 0.0001). From our data, we conclude that the canine pancreas has the capacity to transform sex steroid hormones, and could be considered an extragonadal site of sex steroid biosynthesis.

  18. Distribution of beta-amyloid in the canine brain.

    Science.gov (United States)

    Hou, Y; White, R G; Bobik, M; Marks, J S; Russell, M J

    1997-03-01

    The distribution of amyloid-beta protein (A beta) in the canine brain was demonstrated by immunochemistry on serially sectioned tissues from 10 aged mixed breed dogs. Summation of quantitative data and relegation to anatomical sites for the 10 dogs showed A beta to be widely distributed in the cortex and hippocampus while completely absent in the brain stem and cerebellum. The highest density of A beta was in the dentate gyrus of the hippocampus. Cortical areas exhibiting the greatest A beta deposition were the posterior and medial suprasylvius gyrus and the proreus gyrus of the frontal lobe. Unlike humans the canine entorhinal cortex, amygdala, basal ganglia and olfactory bulbs were rarely affected. This suggested that the highly developed olfactory pathways of the canine are generally spared from A beta deposition. PMID:9141082

  19. Severe canine distemper outbreak in unvaccinated dogs in Mozambique.

    Science.gov (United States)

    Zacarias, Julieta; Dimande, Alberto; Achá, Sara; Dias, Paula T; Leonel, Elisa M; Messa, Aurora; Macucule, Baltazar; Júnior, José L; Bila, Custódio G

    2016-01-01

    Although significant animal suffering caused by preventable diseases is frequently seen in developing countries, reports of this are scarce. This report describes avoidable animal suffering owing to a suspected canine distemper (CD) outbreak in unvaccinated dogs owned by low-income families in Mozambique that killed approximately 200 animals. Affected dogs exhibited clinical signs, and gross and microscopic lesions compatible with CD. Immunohistochemical staining confirmed the presence of canine distemper virus (CDV) in the kidney of one dog from the cohort. This brief communication again illustrates that large outbreaks of CDV in unvaccinated dogs occur and that large-scale avoidable suffering and threats to the health of dogs and wild canines continue. Mass vaccination supported by government and non-government organisations is recommended. PMID:27543040

  20. Orthodontic-surgical treatment of bilateral maxillary canine impaction

    Directory of Open Access Journals (Sweden)

    Sumitra

    2012-01-01

    Full Text Available A 13-year-old female patient reported with the chief complaint of irregular front teeth. She had a skeletal Class III and Angle′s Class I malocclusion with hyperdivergent growth pattern and bilateral impaction of maxillary canines. Surgical exposure of the impacted teeth and orthodontic alignment was planned. The surgical exposure was done by a minimally invasive modified window technique. Orthodontic treatment of impacted canines without causing significant morbidity to the adjacent teeth and periodontium is a challenge. The bilaterally impacted maxillary canines were successfully aligned and leveled. The depth of the gingival sulcus and clinical crown heights of disimpacted teeth were normal post-treatment and after 1 year of retention.

  1. Complex odontoma associated to a primary maxillary canine: case report

    Directory of Open Access Journals (Sweden)

    Estela Maris LOSSO

    2009-06-01

    Full Text Available Introduction: Odontomas are malformations of the dental tissues and may interfere with the eruption of the associated tooth. The early diagnosis, followed by a proper treatment at the right time, will result in a favorable prognosis and a desirable occlusion development. Complex odontomas associated to primary teeth are rare. Case report and conclusion: This article describes a case of a complex odontoma in a four-year-old girl that prevented eruption of the left primary canine. The treatment choice was enucleation of the odontoma and the maintenance of the left primary canine.In this case, complete removal of the complex odontoma was successfully conducted, since after one year of follow-up the primary maxillary canine restarted its eruption process.

  2. Characterization of canine platelet adhesion to extracellular matrix proteins.

    Science.gov (United States)

    Pelagalli, Alessandra; Pero, Maria Elena; Mastellone, Vincenzo; Cestaro, Anna; Signoriello, Simona; Lombardi, Pietro; Avallone, Luigi

    2011-07-01

    Canine platelets have been extensively studied but little is known about specific aspects such as adhesion. Platelet adhesion is a critical step during haemostasis and thrombosis as well as during inflammatory and immunopathogenic responses. The aim of this study was to evaluate the adhesive properties of canine platelets using fibrinogen and collagen as substrates immobilized on plates. Adhesion was monitored for 120 min and the effect of adenosine 5'-diphosphate (ADP) was assayed. The results showed that canine platelets displayed good adhesion activity that was significantly time-dependent. Moreover, ADP was able to enhance platelet adhesion in a dose-dependent manner. The findings aid knowledge of the adhesion process and suggest a specific role of surface platelet receptors in mediating the interaction with extracellular matrix proteins.

  3. Management of impacted all canines with surgical exposure and alignment by orthodontic treatment

    Directory of Open Access Journals (Sweden)

    Radha Katiyar

    2013-01-01

    Full Text Available Canine impaction is a dental problem very often encountered in orthodontic practice. After the third molar, the canine is the most frequently impacted tooth. Bringing the impacted canine into a normal position is important for functional occlusion and the final esthetics of the orthodontic treatment. This article illustrates a peculiar case, in which all four permanent canines maintained their unerupted status at age of 16 years. All four impacted canines were surgically exposed, attachment bonded, traction given with K-9 spring and ideally positioned with fixed orthodontic mechanotherapy.

  4. Canine distemper spillover in domestic dogs from urban wildlife.

    Science.gov (United States)

    Kapil, Sanjay; Yeary, Teresa J

    2011-11-01

    Canine distemper virus (CDV) causes a major disease of domestic dogs that develops as a serious systemic infection in unvaccinated or improperly vaccinated dogs. Domesticated dogs are the main reservoir of CDV, a multihost pathogen. This virus of the genus Morbillivirus in the family Paramyxoviridae occurs in other carnivorous species including all members of the Canidae and Mustelidae families and in some members of the Procyonidae, Hyaenidae, Ursidae, and Viverridae families. Canine distemper also has been reported in the Felidae family and marine mammals. The spread and incidences of CDV epidemics in dogs and wildlife here and worldwide are increasing. PMID:22041204

  5. Survey of Canine Dirofilaria immitis Infection in New Caledonia

    OpenAIRE

    Watier-Grillot, S.; J.-L. Marié; Cabre, O.; Davoust, B

    2011-01-01

    Canine dirofilariosis is a frequent parasitic disease in New-Caledonia. A survey of canine heartworm (Dirofilaria immitis) infection among dogs from the cities of Tontouta, Nandaï and Nouméa, was performed in March 2009 using two antigen test kits; the microwell ELISA test: DiroCHE (Synbiotics Europe) and the Rapid Immuno Migration ( R I M ) test: WITNESS DIROFILARIA (Synbiotics Europe). Blood samples were collected from 64 dogs: 49 strays and 15 military working dogs. The military dogs recei...

  6. Orthodontic-surgical treatment of four impacted canines in an adult patient: A case report

    Directory of Open Access Journals (Sweden)

    Pavlović Jasna

    2016-01-01

    Full Text Available Introduction. Full impaction of canines, in both jaws, is a rare phenomenon. It is usually coupled with the persistence of deciduous canines, or any other irregularity in the dental arch. Case report. Panoramic radiograph of a 24-year-old female patient showed bilateral canine impaction in both jaws. Due to vestibular, apical and medial position of canines in the upper jaw, the surgical approach implied the apically positioned flap technique. The position of impacted mandibular canines was vertical with more coronal position relative to the upper canines, thus requiring a closed eruption technique. Conclusion. Inadequate position of impacted canines in the bone fully justifies the use of orthodontic-surgical treatment.

  7. Identification of quantitative trait loci (QTL for canine hip dysplasia and canine elbow dysplasia in Bernese mountain dogs.

    Directory of Open Access Journals (Sweden)

    Sophia Pfahler

    Full Text Available A genome-wide association study for canine hip dysplasia (CHD and canine elbow dysplasia (CED using the Illumina canine high density bead chip had been performed for 174 Bernese mountain dogs. General and mixed linear model analysis identified two different regions with single nucleotide polymorphisms (SNPs on dog chromosome (CFA 14 significantly associated with CHD and a further significantly CHD-associated region on CFA37. For CED, four SNPs on CFA11 and 27 were significantly associated. The identified SNPs of four associated regions included nearby candidate genes. These possible positional candidates were the genes PON2 on CFA14 and FN1 on CFA37 for CHD and the genes LMNB1 on CFA11 and WNT10B on CFA27 for CED.

  8. Potentiation of the Anti-Tumor Effect of Merocyanine 540-Mediated Photodynamic Therapy by Amifostine and Amphotericin B

    OpenAIRE

    Tsujino, Ichiro; Miyagi, Kiyoko; Sampson, Reynée W.; Sieber, Fritz

    2006-01-01

    Leukemia and lymphoma cells are much more sensitive to Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) than normal pluripotent hematopoietic stem cells and normal granulocyte/macrophage progenitors (CFU-GM). By contrast, most solid tumor cells are only moderately sensitive to MC540-PDT. The limited activity against solid tumor cells has detracted from MC540's appeal as a broad-spectrum purging agent. We report here that non-cytotoxic concentrations of amifostine (Ethyol, Ethiofos,...

  9. Transcriptome Analysis of Individual Stromal Cell Populations Identifies Stroma-Tumor Crosstalk in Mouse Lung Cancer Model

    OpenAIRE

    Hyejin Choi; Jianting Sheng; Dingcheng Gao; Fuhai Li; Anna Durrans; Seongho Ryu; Sharrell B. Lee; Navneet Narula; Shahin Rafii; Olivier Elemento; Nasser K. Altorki; Stephen T.C. Wong; Vivek Mittal

    2015-01-01

    Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC) has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer. RNA deep-sequencing analysis of individually sorted myeloid lineage and tumor epithelial c...

  10. Limited transplantation of antigen-expressing hematopoietic stem cells induces long-lasting cytotoxic T cell responses.

    Directory of Open Access Journals (Sweden)

    Warren L Denning

    Full Text Available Harnessing the ability of cytotoxic T lymphocytes (CTLs to recognize and eradicate tumor or pathogen-infected cells is a critical goal of modern immune-based therapies. Although multiple immunization strategies efficiently induce high levels of antigen-specific CTLs, the initial increase is typically followed by a rapid contraction phase resulting in a sharp decline in the frequency of functional CTLs. We describe a novel approach to immunotherapy based on a transplantation of low numbers of antigen-expressing hematopoietic stem cells (HSCs following nonmyeloablative or partially myeloablative conditioning. Continuous antigen presentation by a limited number of differentiated transgenic hematopoietic cells results in an induction and prolonged maintenance of fully functional effector T cell responses in a mouse model. Recipient animals display high levels of antigen-specific CTLs four months following transplantation in contrast to dendritic cell-immunized animals in which the response typically declines at 4-6 weeks post-immunization. Majority of HSC-induced antigen-specific CD8+ T cells display central memory phenotype, efficiently kill target cells in vivo, and protect recipients against tumor growth in a preventive setting. Furthermore, we confirm previously published observation that high level engraftment of antigen-expressing HSCs following myeloablative conditioning results in tolerance and an absence of specific cytotoxic activity in vivo. In conclusion, the data presented here supports potential application of immunization by limited transplantation of antigen-expressing HSCs for the prevention and treatment of cancer and therapeutic immunization of chronic infectious diseases such as HIV-1/AIDS.

  11. Brazilian canine hepatozoonosis Hepatozoonose canina brasileira

    Directory of Open Access Journals (Sweden)

    Lucia Helena O'Dwyer

    2011-09-01

    Full Text Available The genus Hepatozoon includes hundreds of species that infect birds, reptiles, amphibians and mammals, in all continents with tropical and subtropical climates. Two species have been described in domestic dogs: H. canis, reported in Europe, Asia, Africa, South America and the United States; and H. americanum, which so far has only been diagnosed in the United States. In Brazil, the only species found infecting dogs is H. canis. The objective of this review was to detail some aspects of canine hepatozoonosis, caused by H. canis, and the main points of its biology, transmission, pathogenicity, symptoms, epidemiology and diagnostic methods, with emphasis on research developed in Brazil.O gênero Hepatozoon compreende centenas de espécies que infectam aves, répteis, anfíbios e mamíferos, em todos os continentes de clima tropical e subtropical. No cão doméstico duas espécies são descritas, H. canis e H. americanum; a primeira presente na Europa, Ásia, África, América do Sul e nos Estados Unidos da América do Norte (EUA, e a segunda, diagnosticada até o momento somente nos EUA. No Brasil, a espécie que infecta o cão foi caracterizada como H. canis. Esta revisão objetiva detalhar alguns aspectos da hepatozoose canina, causada pelo H. canis e principais pontos de biologia, transmissão, patogenia e sintomas, epidemiologia e métodos de diagnóstico, enfatizando as pesquisas desenvolvidas no Brasil.

  12. Radiographic imaging of the canine intercondylar fossa

    International Nuclear Information System (INIS)

    The intercondylar fossa is believed to play an important role in the pathology of cranial cruciate ligament rupture and therefore has received considerable attention in the last decade. Accurate radiographic imaging of the intercondylar fossa requires that the central x-ray beam pass through the center of the intercondylar “tunnel”. The anatomy of the canine intercondylar fossa is similar to humans, however, the orientations of the intercondylar fossa's differ. Consequently, the positioning techniques described for humans are not appropriate for the dog. To pass through the center of the dog, intercondylar fossa, the central x-ray beam should be 12° (S.D. 1.7°) caudal from the femoral diaphysis in the sagittal plane and obliqued caudolateral to craniomedial 7° (S.D. 0.60°) (caudo78°proximo7° lateralcraniodistomedial oblique). Cross table positioning was used with the hip flexed and the radiograph cassette placed on the cranial surface of the stifle. However, superimposition of the tuber ischii and soft tissues caudal to the femur made 15° to 20° the best angle obtainable. There was not a significant difference (p = 0.17) in the notch width index between a 12° versus 20° angle of the central x-ray beam caudal to the femoral diaphysis, both with 7° of external rotation of the stifle. The notch width index of 0.252 obtained from radiographic measurements was not significantly different from measurements obtained grossly of 0.254 (n = 26; p = 0.69). Failure to oblique the central x-ray beam caused a significant (p = 0.0008) decrease in the apparent fossa width radiographically

  13. Myogenic potential of canine craniofacial satellite cells

    Directory of Open Access Journals (Sweden)

    Rita Maria Laura La Rovere

    2014-05-01

    Full Text Available The skeletal fibres have different embryological origin; the extraocular and jaw-closer muscles develop from prechordal mesoderm while the limb and trunk muscles from somites. These different origins characterise also the adult muscle stem cells, known as satellite cells (SCs and responsible for the fibre growth and regeneration. The physiological properties of presomitic SCs and their epigenetics are poorly studied despite their peculiar characteristics to preserve muscle integrity during chronic muscle degeneration. Here we isolated SCs from canine somitic (SDM: vastus lateralis, rectus abdominus, gluteus superficialis, biceps femoris, psoas and presomitic (PSDM: lateral rectus, temporalis and retractor bulbi muscles as myogenic progenitor cells from young and old animals. In addition, SDM and PSDM satellite cells were obtained also from Golden retrievers affected by muscular dystrophy (GRMD. We characterised the lifespan, the myogenic potential and functions and oxidative stress of both somitic and presomitic SCs with the aim to reveal differences with ageing and between healthy and dystrophic animals. The different proliferation rate was consistent with higher telomerase activity in PSDM-SCs compared to SDM-SCs, although restricted at early passages. SDM-SCs express early (Pax7, MyoD and late (MyHC, Myogenin myogenic markers differently from PSDM-SCs resulting in a more efficient and faster cell differentiation. Taken together our results showed that PSDM-SCs elicit a stronger stem cell phenotype compared to SDM ones. Finally, myomiR expression profile reveals a unique epigenetic signature in GRMD satellite cells and miR-206, highly expressed in dystrophic SCs, seems to play a critical role in muscle degeneration. Thus, miR-206 could represent a potential target for novel therapeutic approaches.

  14. Drug resistance in canine multicentric lymphoma

    NARCIS (Netherlands)

    Zandvliet, M.M.J.M.

    2014-01-01

    Lymphoma is amongst the most common forms of cancer in the dog and is routinely treated with a multidrug chemotherapy protocol that includes (as a minimum) doxorubicin and prednisolone. Despite initial good treatment results (complete response rate ±80%), the tumor will recur in the majority of dogs

  15. DNMT3A and TET2 in the Pre-Leukemic Phase of Hematopoietic Disorders

    Science.gov (United States)

    Sato, Hanae; Wheat, Justin C.; Steidl, Ulrich; Ito, Keisuke

    2016-01-01

    In recent years, advances in next-generation sequencing (NGS) technology have provided the opportunity to detect putative genetic drivers of disease, particularly cancers, with very high sensitivity. This knowledge has substantially improved our understanding of tumor pathogenesis. In hematological malignancies such as acute myeloid leukemia and myelodysplastic syndromes, pioneering work combining multi-parameter flow cytometry and targeted resequencing in leukemia have clearly shown that different classes of mutations appear to be acquired in particular sequences along the hematopoietic differentiation hierarchy. Moreover, as these mutations can be found in “normal” cells recovered during remission and can be detected at relapse, there is strong evidence for the existence of “pre-leukemic” stem cells (pre-LSC). These cells, while phenotypically normal by flow cytometry, morphology, and functional studies, are speculated to be molecularly poised to transform owing to a limited number of predisposing mutations. Identifying these “pre-leukemic” mutations and how they propagate a pre-malignant state has important implications for understanding the etiology of these disorders and for the development of novel therapeutics. NGS studies have found a substantial enrichment for mutations in epigenetic/chromatin remodeling regulators in pre-LSC, and elegant genetic models have confirmed that these mutations can predispose to a variety of hematological malignancies. In this review, we will discuss the current understanding of pre-leukemic biology in myeloid malignancies, and how mutations in two key epigenetic regulators, DNMT3A and TET2, may contribute to disease pathogenesis. PMID:27597933

  16. Relapse risk in patients with malignant diseases given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.

    Science.gov (United States)

    Kahl, Christoph; Storer, Barry E; Sandmaier, Brenda M; Mielcarek, Marco; Maris, Michael B; Blume, Karl G; Niederwieser, Dietger; Chauncey, Thomas R; Forman, Stephen J; Agura, Edward; Leis, Jose F; Bruno, Benedetto; Langston, Amelia; Pulsipher, Michael A; McSweeney, Peter A; Wade, James C; Epner, Elliot; Bo Petersen, Finn; Bethge, Wolfgang A; Maloney, David G; Storb, Rainer

    2007-10-01

    Allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies depends on graft-versus-tumor effects for eradication of cancer. Here, we estimated relapse risks according to disease characteristics. Between 1997 and 2006, 834 consecutive patients (median age, 55 years; range, 5-74 years) received related (n = 498) or unrelated (n = 336) HCT after 2 Gy total body irradiation alone (n = 171) or combined with fludarabine (90 mg/m(2); n = 663). Relapse rates per patient year (PY) at risk, corrected for follow-up and competing nonrelapse mortality, were calculated for 29 different diseases and stages. The overall relapse rate per PY was 0.36. Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) in remission (CR), low-grade or mantle cell non-Hodgkin lymphoma (NHL) (CR + partial remission [PR]), and high-grade NHL-CR had the lowest rates (0.00-0.24; low risk). In contrast, patients with advanced myeloid and lymphoid malignancies had rates of more than 0.52 (high risk). Patients with lymphoproliferative diseases not in CR (except Hodgkin lymphoma and high-grade NHL) and myeloid malignancies in CR had rates of 0.26-0.37 (standard risk). In conclusion, patients with low-grade lymphoproliferative disorders experienced the lowest relapse rates, whereas patients with advanced myeloid and lymphoid malignancies had high relapse rates after nonmyeloablative HCT. The latter might benefit from cytoreductive treatment before HCT.

  17. Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually.

    Science.gov (United States)

    Passweg, J R; Baldomero, H; Bader, P; Bonini, C; Cesaro, S; Dreger, P; Duarte, R F; Dufour, C; Kuball, J; Farge-Bancel, D; Gennery, A; Kröger, N; Lanza, F; Nagler, A; Sureda, A; Mohty, M

    2016-06-01

    A record number of 40 829 hematopoietic stem cell transplantation (HSCT) in 36 469 patients (15 765 allogeneic (43%), 20 704 autologous (57%)) were reported by 656 centers in 47 countries to the 2014 survey. Trends include: continued growth in transplant activity, more so in Eastern European countries than in the west; a continued increase in the use of haploidentical family donors (by 25%) and slower growth for unrelated donor HSCT. The use of cord blood as a stem cell source has decreased again in 2014. Main indications for HSCT were leukemias: 11 853 (33%; 96% allogeneic); lymphoid neoplasias; 20 802 (57%; 11% allogeneic); solid tumors; 1458 (4%; 3% allogeneic) and non-malignant disorders; 2203 (6%; 88% allogeneic). Changes in transplant activity include more allogeneic HSCT for AML in CR1, myeloproliferative neoplasm (MPN) and aplastic anemia and decreasing use in CLL; and more autologous HSCT for plasma cell disorders and in particular for amyloidosis. In addition, data on numbers of teams doing alternative donor transplants, allogeneic after autologous HSCT, autologous cord blood transplants are presented.

  18. DNMT3A and TET2 in the Pre-Leukemic Phase of Hematopoietic Disorders.

    Science.gov (United States)

    Sato, Hanae; Wheat, Justin C; Steidl, Ulrich; Ito, Keisuke

    2016-01-01

    In recent years, advances in next-generation sequencing (NGS) technology have provided the opportunity to detect putative genetic drivers of disease, particularly cancers, with very high sensitivity. This knowledge has substantially improved our understanding of tumor pathogenesis. In hematological malignancies such as acute myeloid leukemia and myelodysplastic syndromes, pioneering work combining multi-parameter flow cytometry and targeted resequencing in leukemia have clearly shown that different classes of mutations appear to be acquired in particular sequences along the hematopoietic differentiation hierarchy. Moreover, as these mutations can be found in "normal" cells recovered during remission and can be detected at relapse, there is strong evidence for the existence of "pre-leukemic" stem cells (pre-LSC). These cells, while phenotypically normal by flow cytometry, morphology, and functional studies, are speculated to be molecularly poised to transform owing to a limited number of predisposing mutations. Identifying these "pre-leukemic" mutations and how they propagate a pre-malignant state has important implications for understanding the etiology of these disorders and for the development of novel therapeutics. NGS studies have found a substantial enrichment for mutations in epigenetic/chromatin remodeling regulators in pre-LSC, and elegant genetic models have confirmed that these mutations can predispose to a variety of hematological malignancies. In this review, we will discuss the current understanding of pre-leukemic biology in myeloid malignancies, and how mutations in two key epigenetic regulators, DNMT3A and TET2, may contribute to disease pathogenesis. PMID:27597933

  19. Inflammatory Response Using Different Lipid Parenteral Nutrition Formulas in Children After Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Baena-Gómez, María Auxiliadora; de la Torre-Aguilar, María José; Aguilera-García, Concepción María; Olza, Josune; Pérez-Navero, Juan Luis; Gil-Campos, Mercedes

    2016-07-01

    Nutritional support is an integral part of the supportive care of hematopoietic stem cell transplantation (HSCT) patients. Omega-3 fatty acids (n-3 FA) emulsions in parenteral nutrition (PN) may modify the inflammatory response. The purpose of this study is to compare plasma cytokine levels in children after HSCT using an n-3 FA-containing lipid emulsion (LE) and a soybean oil-based formulation in PN. A randomized double-blind controlled trial was conducted on 14 children following HSCT. Children were randomized to receive either a fish oil or a soybean oil LE. Blood samples were drawn at baseline, on Day 10 and after completion of PN to analyze plasma interleukin 1 beta (IL-1β), 2 (IL-2), 6 (IL-6), 8 (IL-8), 10 (IL-10), and tumor necrosis factor alpha (TNF-α). After 10 days of PN, there were no significant changes in interleukins levels when comparing the two groups or time points (baseline vs. Day 10 of PN). In children requiring PN >21 days, IL-10 and TNF-α levels (P ≤ 0.05) were lower in the fish-oil-containing LE group. Fish oil- and soybean oil-supplemented PN administered for at least 10 days does not cause inflammatory changes. Prolonged PN based on fish oil LE may modulate the inflammatory response. PMID:27270245

  20. Accelerated tumor progression in mice lacking the ATP receptor P2X7

    DEFF Research Database (Denmark)

    Adinolfi, Elena; Capece, Marina; Franceschini, Alessia;

    2015-01-01

    cells. Tumor size and metastatic dissemination were assessed by in vivo calliper and luciferase luminescence emission measurements along with postmortem examination. In P2X7R-deficient mice, tumor growth and metastatic spreading were accelerated strongly, compared with wild-type (wt) mice. Intratumoral...... IL-1β and VEGF release were drastically reduced, and inflammatory cell infiltration was abrogated nearly completely. Similarly, tumor growth was also greatly accelerated in wt chimeric mice implanted with P2X7R-deficient bone marrow cells, defining hematopoietic cells as a sufficient site of P2X7R...