Sample records for canine hemangiosarcoma xenograft

  1. Interleukin-12 Inhibits Tumor Growth in a Novel Angiogenesis Canine Hemangiosarcoma Xenograft Model

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    Nasim Akhtar


    Full Text Available We established a canine hemangiosarcoma cell line derived from malignant endothelial cells comprising a spontaneous tumor in a dog to provide a renewable source of endothelial cells for studies of angiogenesis in malignancy. Pieces of the hemangiosarcoma biopsy were engrafted subcutaneously in a bg/nu/XID mouse allowing the tumor cells to expand in vivo. A cell line, SB-HSA, was derived from the xenograft. SB-HSA cells expressed vascular endothelial growth factor (VEGF receptors 1 and 2, CD31, CD146, and αvβ3 integrin, and produced several growth factors and cytokines, including VEGF, basic fibroblast growth factor, and interleukin (IL-8 that are stimulatory to endothelial cell growth. These results indicated that the cells recapitulated features of mitotically activated endothelia. In vivo, SB-HSA cells stimulated robust angiogenic responses in mice and formed tumor masses composed of aberrant vascular channels in immunocompromised mice providing novel opportunities for investigating the effectiveness of antiangiogenic agents. Using this model, we determined that IL-12, a cytokine with both immunostimulatory and antiangiogenic effects, suppressed angiogenesis induced by, and tumor growth of, SB-HSA cells. The endothelial cell model we have described offers unique opportunities to pursue further investigations with IL-12, as well as other antiangiogenic approaches in cancer therapy.

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

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    Maruo Kouji


    Full Text Available Abstract Background 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. Methods 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. Results 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

  3. Pharmacologic inhibition of MEK signaling prevents growth of canine hemangiosarcoma (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.


    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

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

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    Kim, Jong-Hyuk, E-mail: [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: [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)


    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

  5. Gene expression profiling identifies inflammation and angiogenesis as distinguishing features of canine hemangiosarcoma

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    Slansky Jill E


    Full Text Available Abstract Background The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease. Methods We first investigated mutations of VHL and Ras family genes that might drive hemangiosarcoma by sequencing tumor DNA and mRNA (cDNA. Protein expression was examined using immunostaining. Next, we evaluated genome-wide gene expression profiling using the Affymetrix Canine 2.0 platform as a global approach to test the hypothesis. Data were evaluated using routine bioinformatics and validation was done using quantitative real time RT-PCR. Results Each of 10 tumor and four non-tumor samples analyzed had wild type sequences for these genes. At the genome wide level, hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on a robust signature that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. This signature did not simply reflect a cancer-associated angiogenic phenotype, as it also distinguished hemangiosarcoma from non-endothelial, moderately to highly angiogenic bone marrow-derived tumors (lymphoma, leukemia, osteosarcoma. Conclusions The data show that inflammation and angiogenesis are important processes in the pathogenesis of vascular tumors, but a definitive ontogeny of the cells that give rise to these tumors remains to be established. The data do not yet distinguish whether functional or ontogenetic

  6. Gene expression profiles of sporadic canine hemangiosarcoma are uniquely associated with breed.

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    Beth A Tamburini

    Full Text Available The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression profiling in a naturally occurring endothelial sarcoma of dogs (hemangiosarcoma. Naturally occurring hemangiosarcomas of Golden Retrievers clustered separately from those of non-Golden Retrievers, with contributions from transcription factors, survival factors, and from pro-inflammatory and angiogenic genes, and which were exclusively present in hemangiosarcoma and not in other tumors or normal cells (i.e., they were not due simply to variation in these genes among breeds. Vascular Endothelial Growth Factor Receptor 1 (VEGFR1 was among genes preferentially enriched within known pathways derived from gene set enrichment analysis when characterizing tumors from Golden Retrievers versus other breeds. Heightened VEGFR1 expression in these tumors also was apparent at the protein level and targeted inhibition of VEGFR1 increased proliferation of hemangiosarcoma cells derived from tumors of Golden Retrievers, but not from other breeds. Our results suggest heritable factors mold gene expression phenotypes, and consequently biological behavior in sporadic, naturally occurring tumors.

  7. Doxorubicin and deracoxib adjuvant therapy for canine splenic hemangiosarcoma: a pilot study. (United States)

    Kahn, S Anthony; Mullin, Christine M; de Lorimier, Louis-Philippe; Burgess, Kristine E; Risbon, Rebecca E; Fred, Rogers M; Drobatz, Kenneth; Clifford, Craig A


    Canine hemangiosarcoma (HSA) is a highly malignant tumor for which standard chemotherapy has done little to substantially improve survival. Cyclooxygenase-2 (Cox-2) plays a role in the formation, growth, and metastasis of tumors and inhibitors have demonstrated therapeutic benefit with certain canine cancers. In this prospective study, 21 dogs received adjuvant therapy combining the selective Cox-2 inhibitor deracoxib with doxorubicin, following splenectomy for HSA. The combination was well-tolerated with only low-grade gastrointestinal and hematologic toxicities noted. An overall median survival of 150 days (range; 21 to 1506 days) was noted. Although there was no significant difference in survival based upon stage of disease, dogs with stage III HSA (n = 11) had a median survival of 149 days, which appears to be longer than previously reported. Further studies are warranted to evaluate the potential benefit of Cox-2 inhibitors in the treatment of canine HSA.

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

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    Murai Atsuko


    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

  9. Establishment and characterization of a canine xenograft model of inflammatory mammary carcinoma. (United States)

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


    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.

  10. Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model. (United States)

    Choisunirachon, N; Jaroensong, T; Yoshida, K; Saeki, K; Mochizuki, M; Nishimura, R; Sasaki, N; Nakagawa, T


    Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma.

  11. Hepatic hemangiosarcoma: imaging findings and differential diagnosis

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    Rademaker, J.; Galanski, M. [Department of Radiology I, Medical School Hannover (Germany); Widjaja, A. [Department of Gastroenterology and Hepatology, Medical School Hannover (Germany)


    Primary hepatic angiosarcoma is a rare mesenchymal tumor of the liver that usually presents with nonspecific symptoms in elderly men. We present four cases of hepatic hemangiosarcoma and discuss the imaging characteristics of this entity. Our series shows that this tumor is not uncommon in younger patients with no associated risk factors such as previous exposure to thorotrast or vinyl chloride. Our experiences on a limited number of patients suggests that the combined use of angiography and dual-phase helical CT provides a better identification of the tumor and its complications. Analysis of imaging studies in patients with hepatic hemangiosarcoma reveals hypervascular lesions. Common complications were portal vein thrombosis, Budd-Chiari syndrome, as well as arterio-venous or arterio-portal shunts. Due to the vascularity of the tumor, percutaneous liver biopsy is hazardous. (orig.)

  12. [Hepato-splenic hemangiosarcoma: presentation of a clinical case]. (United States)

    Antoniello, L; Cohen, H; Rondán, M; Rodríguez, J; Fosman, E


    A 65-year-old farmer who had used arsenic as a plaguicide for many years developed a hepatosplenic hemangiosarcoma with metastasis in the colonic serosa, mesentery and omental. The tumor was complicated with intraabdominal hemorrhage originated by spontaneous intraperitoneal rupture. The echographic and post-mortem findings are presented. This is the first case of hepatic hemangiosarcoma reported in Uruguay.

  13. Single Agent Polysaccharopeptide Delays Metastases and Improves Survival in Naturally Occurring Hemangiosarcoma

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    Dorothy Cimino Brown


    Full Text Available The 2008 World Health Organization World Cancer Report describes global cancer incidence soaring with many patients living in countries that lack resources for cancer control. Alternative treatment strategies that can reduce the global disease burden at manageable costs must be developed. Polysaccharopeptide (PSP is the bioactive agent from the mushroom Coriolus versicolor. Studies indicate PSP has in vitro antitumor activities and inhibits the growth of induced tumors in animal models. Clear evidence of clinically relevant benefits of PSP in cancer patients, however, is lacking. The investment of resources required to complete large-scale, randomized controlled trials of PSP in cancer patients is more easily justified if antitumor and survival benefits are documented in a complex animal model of a naturally occurring cancer that parallels human disease. Because of its high metastatic rate and vascular origin, canine hemangiosarcoma is used for investigations in antimetastatic and antiangiogenic therapies. In this double-blind randomized multidose pilot study, high-dose PSP significantly delayed the progression of metastases and afforded the longest survival times reported in canine hemangiosarcoma. These data suggest that, for those cancer patients for whom advanced treatments are not accessible, PSP as a single agent might offer significant improvements in morbidity and mortality.

  14. Primary hemangiosarcoma of the spleen with angioscintigraphic demonstration of metastases

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    Hermann, G G; Fogh, J; Graem, N


    99mTc-methylene-diphosphonate (MDP) bone scintigraphy, which showed only a few minor focal changes in the spine and ribs, angioscintigraphy with in vitro labeled 99mTc-erythrocytes revealed extensive pathologic accumulations throughout the spine, femurs, and the liver, indicating the presence...... of extremely vascular metastases. Autopsy 15 months later confirmed the scintigraphic findings. Angiography with 99mTc-labeled erythrocytes seems to be useful for monitoring metastases from hemangiosarcomas....

  15. Evaluation of a canine small intestinal submucosal xenograft and polypropylene mesh as bioscaffolds in an abdominal full-thickness resection model of growing rats. (United States)

    Lee, A-Jin; Lee, Sung-Ho; Chung, Wook-Hun; Kim, Dae-Hyun; Chung, Dai-Jung; Do, Sun Hee; Kim, Hwi-Yool


    We evaluated the biological scaffold properties of canine small intestinal submucosa (SIS) compared to a those of polypropylene mesh in growing rats with full-thickness abdominal defects. SIS is used to repair musculoskeletal tissue while promoting cell migration and supporting tissue regeneration. Polypropylene mesh is a non-resorbable synthetic material that can endure mechanical tension. Canine SIS was obtained from donor German shepherds, and its porous collagen fiber structure was identified using scanning electron microscopy (SEM). A 2.50-cm(2) section of canine SIS (SIS group) or mesh (mesh group) was implanted in Sprague-Dawley rats. At 1, 2, 4, 12, and 24 weeks after surgery, the implants were histopathologically examined and tensile load was tested. One month after surgery, CD68+ macrophage numbers in the SIS group were increased, but the number of CD8+ T cells in this group declined more rapidly than that in rats treated with the mesh. In the SIS group, few adhesions and well-developed autologous abdominal muscle infiltration into the SIS collagen fibers were observed. No significant differences in the tensile load test results were found between the SIS and mesh groups at 24 weeks. Canine SIS may therefore be a suitable replacement for artificial biological scaffolds in small animals.

  16. Hemothorax in Three Dogs with Intrathoracic Extracardiac Hemangiosarcoma. (United States)

    Rutherford, Lynda; Stell, Anneliese; Smith, Ken; Kulendra, Nicola


    Intrathoracic extracardiac hemangiosarcoma (HSA) is rare in dogs. This report describes three dogs with acute onset dyspnea due to hemorrhagic pleural effusion resulting from intrathoracic extracardiac masses, which were confirmed as HSA by histopathology. The dogs were stabilized with thoracocentesis and intravascular fluid resuscitation. Computed tomography identified intrathoracic masses, which were not originating from the heart or pulmonary parenchyma. Surgical exploration was performed in all cases. Case 1 was euthanized intraoperatively as the tumor could not be dissected from the aorta. In cases 2 and 3, hemostasis and resection of the tumors was successful. Case 2 was euthanized 1 mo after surgery and case 3 was alive at the time of writing, 5 mo postoperatively. Intrathoracic extracardiac HSA should be considered as a differential for nontraumatic hemothorax and surgical treatment can be palliative.


    Lindemann, Dana M; Carpenter, James W; Nietfeld, Jerome C; Gonzalez, Estehela; Hallman, Mackenzie; Hause, Ben M


    A 13-yr-old intact male cheetah (Acinonyx jubatus) presented for evaluation after a 4-mo history of intermittent lethargy and increased expiratory effort. The clinical signs were initially noted after the diagnosis and death of its 13-yr-old male sibling with solitary hepatic T-cell lymphoma. Physical examination findings included thin body condition, harsh lung sounds, peripheral lymphadenopathy, and a cutaneous mass on the right medial tarsus and scrotum. Excisional biopsies diagnosed well-differentiated cutaneous hemangiosarcomas. Thoracic radiographs revealed a cranial mediastinal mass. Complete blood count and serum biochemical analyses showed a leukocytosis with persistent lymphocytosis, progressive azotemia, and markedly elevated alkaline phosphatase. Because of the cheetah's declining quality of life, euthanasia was elected. Postmortem examination, histopathology, and immunohistochemical staining revealed multicentric T-cell lymphoma. Feline leukemia virus (FeLV) enzyme-linked immunosorbent assay, FeLV polymerase chain reaction (whole blood), and viral metagenomic analysis were negative. This is the first case of cutaneous hemangiosarcoma and multicentric T-cell lymphoma reported in a FeLV-negative cheetah.

  18. Clinical Description of Metastatic Cutaneous Hemangiosarcoma (HSA in a Greyhound Dog: Clinical Case Study

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    Romy Marie Weinborn Astudillo


    Full Text Available Hemangiosarcoma (HSA is a type of cancer that has different clinical presentations and therefore different effects, since, depending on each case, different treatment options will exist. While in the case of cutaneous HSA the first line of treatment is always surgical removal of the tumor, metastatic foci should be sought and then perform chemotherapy, despite them having a low metastatic potential. Moreover, the low survival that exists in this type of cancer is a factor that should be communicated to those responsible for the pets, so that, with all available information, they can make a free and informed choice about the treatment they want for their pet, considering the financial commitment, survival time and quality of life associated with chemotherapy. This article describes the clinical case of a female greyhound dog of eight years of age that was brought to consultation for a skin tumor on the right hind limb in the distal tibia. She was diagnosed with noninvasive cutaneous HSA through histopathology, reason why the owners chose not to do the chemotherapy; however, 10 months later she presented recurrent skin lesions and a popliteal lymph node corresponding to hemangiosarcoma and hemangioma respectively, and three weeks later the patient developed cardiac tamponade due to a cardiac mass with associated spill, which resulted in her euthanasia.

  19. Canine Distemper (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 ...

  20. Cystadenocarcinoma simulating hemangiosarcoma of the salivary gland in dog: case report

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    C.O. Gamba


    Full Text Available Cystadenocarcinoma is regarded as a rare adenocarcinoma variant in animals. This work reports the case of an 8-year-old female Poodle dog with salivary gland cystadenocarcinoma with morphological characteristics similar to a hemangiosarcoma. Histopathological analysis showed a tumor mass with cystic formations containing a large amount of red blood cells. In order to distinguish these two entities, periodic acid Schiff (PAS staining and immunohistochemical analysis were carried out with the use of cytokeratin AE1/AE3 (CK and CD31-specific antibodies. Neoplastic cells were PAS-negative, CK-positive and CD31-negative confirming their epithelial origin. Based on the findings, the diagnosis of high grade cystadenocarcinoma was established.

  1. Stage-specific embryonic antigen: determining expression in canine glioblastoma, melanoma, and mammary cancer cells (United States)

    Ito, Daisuke


    The expression of stage-specific embryonic antigens (SSEAs) was determined in several types of canine cancer cells. Flow cytometry showed SSEA-1 expression in glioblastoma, melanoma, and mammary cancer cells, although none expressed SSEA-3 or SSEA-4. Expression of SSEA-1 was not detected in lymphoma, osteosarcoma, or hemangiosarcoma cell lines. Relatively stable SSEA-1 expression was observed between 24 and 72 h of culture. After 8 days in culture, sorted SSEA-1− and SSEA-1+ cells re-established SSEA-1 expression to levels comparable to those observed in unsorted cells. Our results document, for the first time, the expression of SSEA-1 in several canine cancer cell lines. PMID:27456773

  2. Canine gastritis. (United States)

    Webb, Craig; Twedt, David C


    Gastritis--inflammation of the stomach--is a frequently cited differential yet rarely characterized diagnosis in cases of canine anorexia and vomiting. Although the list of rule-outs for acute or chronic gastritis is extensive, a review of the veterinary literature reveals fewer than 15 articles that have focused on clinical cases of canine gastritis over the last 25 years. The dog frequently appears in the human literature as an experimentally manipulated model for the study of endoscopic techniques or the effect of medications on gastric mucosa. In the veterinary patient, cases of acute gastritis are rarely pursued with the complete diagnostic armamentarium, and cases of chronic gastritis are rarely found to occur as an entity isolated from the rest of the gastrointestinal tract. This article focuses on those findings most clinically relevant to cases of canine gastritis in veterinary medicine.

  3. Antigen profiling analysis of vaccinia virus injected canine tumors (United States)

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


    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. PMID:25482233

  4. Therapeutic strategies for xenograft rejection. (United States)

    Lin, S S


    The increasing demand for transplantable organs over the past several decades has stimulated the idea of using animal organs in lieu of cadaveric organs in clinical transplantation. Pigs are now considered to be the most suitable source of organs for transplantation because of their abundant availability, their appropriate size, their relatively short gestation period, and the recent development in the technology to genetically manipulate them. In the past few years, some of the seemingly complex immunologic responses in pig-to-primate transplantation have been elucidated. This progress has allowed us to focus our efforts on devising specific therapeutic strategies to overcome or prevent some of the responses that contribute to rejection of the xenograft. In this article, we review the various approaches that might allow clinical xenotransplantation to come to fruition.

  5. Enamel Hypoplasia of Deciduous Canine


    加納, 隆; 平出, 百合子; 舟津, 聡; 峯村, 隆一; 恩田, 千爾; 正木, 岳馬


    From observation of frequency and measurement of the lengths and widths of enamel hypoplasia on the maxillary and mandibular deciduous canines, extracted from 50 Indians' skulls, the following results were obtained. 1) Enamel hypoplasia occurred in 15% of the maxillary deciduous canines and 44% of the mandibular deciduous canines. 2) Symmetrical cases of enamel hypoplasia occurred in 8.0% of the maxillary deciduous canins and in 34% of the mandibular deciduous canines. The enamel hypoplasia o...

  6. Hemangiosarcoma after breast-conserving therapy of breast cancer. Report of four cases with molecular genetic diagnosis and literature review; Haemangiosarkom nach brusterhaltender Therapie beim Mammakarzinom. Vier Fallbeispiele mit molekulargenetischer Diagnostik und Literaturuebersicht

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    Nestle-Kraemling, Carolin [Universitaetsklinikum, Duesseldorf (Germany). Frauenklinik; Boelke, Edwin; Budach, Wilfried [Universitaetsklinikum Duesseldorf (DE). Klinik und Poliklinik fuer Strahlentherapie und radiologische Onkologie] (and others)


    Hemangiosarcomas of the breast represent a rare disease of the breast mainly occurring as secondary neoplasias with a latency of 5-10 years after primary treatment of breast cancer and are associated with an unfavourable prognosis. Radiation therapy, which is integrated within the concept of breast conserving therapy ranks as the main risk factor. In this report we describe the clinical course of 4 patients including their molecular genetic pattern and give a summary of the actual literature. Hemangiosarcomas occur as a secondary neoplasm with a latency of 5-10 years after primary treatment of breast cancer and have an unfavorable prognosis. A genetic predisposition is assumed, but we could not find a significant role of tumor suppressor genes BRCA1, BRCA2 or p53 in our patients. Due to limited data available for these tumors, recommendations for therapy include radical tumor resection achieving wide free margins and inconsistent regimens of chemo- and/or immunetherapy modalities. In the majority these are based on systemic therapy regimens for other cutaneous sarcomas, such as Kaposi's sarcoma. Efforts should be taken for a nation-wide systematic registration of all cases of post-irradiation hemangiosarcomas.

  7. Antigen profiling analysis of vaccinia virus injected canine tumors: oncolytic virus efficiency predicted by boolean models. (United States)

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


    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.

  8. Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior

    Directory of Open Access Journals (Sweden)

    Milcah C. Scott


    Full Text Available Osteosarcoma (OS is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2 for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of

  9. 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.

  10. Vaccines for Canine Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Faeze Foroughi-Parvar


    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.

  11. Canine pulmonary angiostrongylosis

    DEFF Research Database (Denmark)

    Koch, Jørgen; Willesen, Jakob Lundgren


    Canine pulmonary angiostrongylosis is an emerging snail-borne disease causing verminous pnemonia and coagulopathy in dogs. The parasite is fund in Europe, North and South America and Africa, covering tropical, subtropical and temperate regions. Its distribution has been characterised by isolated ...

  12. Vaccines for canine leishmaniasis

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    Clarisa B. Palatnik-De-Sousa


    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

  13. Virotherapy of canine tumors with oncolytic vaccinia virus GLV-1h109 expressing an anti-VEGF single-chain antibody.

    Directory of Open Access Journals (Sweden)

    Sandeep S Patil

    Full Text Available Virotherapy using oncolytic vaccinia virus (VACV strains is one promising new strategy for cancer therapy. We have previously reported that oncolytic vaccinia virus strains expressing an anti-VEGF (Vascular Endothelial Growth Factor single-chain antibody (scAb GLAF-1 exhibited significant therapeutic efficacy for treatment of human tumor xenografts. Here, we describe the use of oncolytic vaccinia virus GLV-1h109 encoding GLAF-1 for canine cancer therapy. In this study we analyzed the virus-mediated delivery and production of scAb GLAF-1 and the oncolytic and immunological effects of the GLV-1h109 vaccinia virus strain against canine soft tissue sarcoma and canine prostate carcinoma in xenograft models. Cell culture data demonstrated that the GLV-1h109 virus efficiently infect, replicate in and destroy both tested canine cancer cell lines. In addition, successful expression of GLAF-1 was demonstrated in virus-infected canine cancer cells and the antibody specifically recognized canine VEGF. In two different xenograft models, the systemic administration of the GLV-1h109 virus was found to be safe and led to anti-tumor and immunological effects resulting in the significant reduction of tumor growth in comparison to untreated control mice. Furthermore, tumor-specific virus infection led to a continued production of functional scAb GLAF-1, resulting in inhibition of angiogenesis. Overall, the GLV-1h109-mediated cancer therapy and production of immunotherapeutic anti-VEGF scAb may open the way for combination therapy concept i.e. vaccinia virus mediated oncolysis and intratumoral production of therapeutic drugs in canine cancer patients.

  14. Radioimmunodetection of human choriocarcinoma xenograft in nude mouse

    Institute of Scientific and Technical Information of China (English)


    Objective: To study the efficiency of radioimmuno-detection in locating the xenograft of human chorio-carcinoma in nude mouse. Methods: Radioimmuno-detection was performed using cocktail antibodies of 131I-labeled mouse anti-human chorionic gonadotropin monoclonal antibodies to locate the xenograft of human choriocarcinoma in nude mouse. Radioactivity in different tissues was measured and the tumor/non-tumor ratio was calculated. Normal mouse IgG was used as control IgG. Results: The accumulation of radioactivity in the xenograft area could be recognized as early as 24 h after the injection of the radiolabelled antibodies. 72-96 h after the injection, the xenograft could be clearly shown. The minimal shown xenograft was 0.8 cm in diameter. The tumor/non-tumor ratio increased with the time and was obviously higher than that in control group. Conclusion: Radioimmunodetection can efficiently locate human choriocarcinoma xenograft in nude mouse.

  15. [Canine histoplasmosis in Japan]. (United States)

    Sano, Ayako; Miyaji, Makoto


    Histoplasmosis is a fungal infection caused by Histoplasma capsulatum and is distributed a worldwide. Although the disease has been treated as an imported mycosis, some autochthonous human, 1 equine and 4 canine cases suggested that the disease is endemic. Histoplasmosis is classified depending on the variety of causative agent. Histoplasmosis farciminosi known as pseudofarcy, is manifested only in Perissodactyla where it invades lymph nodes and lymph ducts, and is recognized by isolation from horses. Historically, Japan was one of the endemic areas of pseudofarcy before World War II, and more than 20,000 cases were recorded in horses used by the military. Interestingly, Japanese canine histoplasmosis uniformly showed skin ulcers and granulomatous lesions on the skin without pulmonary or gastrointestinal involvement, both of which were very similar to pseudofarcy. It was diagnosed as histoplasmosis by the detection of internal transcribed spacer legions of rRNA gene of H. capsulatum from paraffin embedded tissue samples. Furthermore, the fungal isolate from the human case with no history of going abroad or immigrating was identified as H. capsulatum var. farciminosum by a gene sequence. These facts indicated that pseudofarcy is not only an infectious disease in horses, but also a zoonotic fungal infection. Japanese autochthonous canine histoplasmosis might be a heteroecism of pseudofarcy because of its likeness to the human case, the similarity of clinical manifestations and the historical background at this stage.

  16. Molecular imaging of cyclooxygenase-2 in canine transitional cell carcinomas in vitro and in vivo. (United States)

    Cekanova, Maria; Uddin, Md Jashim; Bartges, Joseph W; Callens, Amanda; Legendre, Alfred M; Rathore, Kusum; Wright, Laura; Carter, Amanda; Marnett, Lawrence J


    The enzyme COX-2 is induced at high levels in tumors but not in surrounding normal tissues, which makes it an attractive target for molecular imaging of cancer. We evaluated the ability of novel optical imaging agent, fluorocoxib A to detect urinary bladder canine transitional cell carcinomas (K9TCC). Here, we show that fluorocoxib A uptake overlapped with COX-2 expression in primary K9TCC cells in vitro. Using subcutaneously implanted primary K9TCC in athymic mice, we show specific uptake of fluorocoxib A by COX-2-expressing K9TCC xenograft tumors in vivo. Fluorocoxib A uptake by COX-2-expressing xenograft tumors was blocked by 70% (P dogs diagnosed with TCC. Fluorocoxib A specifically detected COX-2-expressing K9TCC during cystoscopy in vivo but was not detected in normal urothelium. Taken together, our findings show that fluorocoxib A selectively bound to COX-2-expressing primary K9TCC cells in vitro, COX-2-expressing K9TCC xenografts tumors in nude mice, and heterogeneous canine TCC during cystoscopy in vivo. Spontaneous cancers in companion animals offer a unique translational model for evaluation of novel imaging and therapeutic agents using primary cancer cells in vitro and in heterogeneous cancers in vivo.

  17. Restoration of missing or misplaced canines. (United States)

    Bower, C F; Reinhardt, R A


    Restorative treatments for canines were discussed to correct three clinical abnormalities: (1) fully erupted permanent canine in the lateral incisor position, (2) missing permanent canines, and (3) partially exposed canines in normal arch position. The primary concerns are the development of esthetics, anterior guidance, and adequate support for fixed restorations.

  18. Canine mammary gland tumors. (United States)

    Sorenmo, Karin


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

  19. Characterization of spheres derived from canine mammary gland adenocarcinoma cell lines. (United States)

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


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

  20. Paravertebral cutaneous hemangiosarcoma in dog causing medular compression / Hemangiossarcoma cutâneo paravertebral em cão causando compressão medular

    Directory of Open Access Journals (Sweden)

    Ana Paula Frederico Rodrigues Loureiro Bracarense


    Full Text Available A seven-year-old male Scottish terrier was examined at the Veterinary Hospital of the Universidade Estadual de Londrina due to a toracolumbar syndrome classified as V degree and a mass in lumbar region back right of slow growth with evaluation of two months. Myelography showed an interruption of the column of contrast between the 11th and 12th thoracic vertebrae. A hemilaminectomy was performed in this region. Spinal cord compression at this location was not observed, however during the caudal enlargement of hemilaminectomy it was visualized in the region of the fourth lumbar vertebrae, a spinal cord deviation to the left, due to the presence of a reddish mass at the right side that was diagnosed as a tumor infiltration in the vertebrae with cord compression. Surgical removal with appropriate margin was not possible. In histology, the tumor was classified as hemangiosarcoma. This report emphasizes the importance of considering the possibility of cancer as differential diagnosis of paraplegias, even in acute clinical changes.Um cão macho, Scottish Terrier, de sete anos foi atendido no Hospital Veterinário da Universidade Estadual de Londrina por apresentar paraplegia grau V e um nódulo em região dorso lombar direita de crescimento lento, com evolução de dois meses. Foi realizado mielografia, visibilizando-se interrupção na coluna de contraste entre as vértebras torácicas 11ª e 12ª. Assim, procedeu-se à hemilaminectomia nesta região, não sendo constatado compressão medular, procedendo-se a ampliação caudal da abertura da lâmina vertebral T12. Na região da quarta vértebra lombar observou-se um desvio da medula espinhal para o lado esquerdo devido à presença de uma massa de coloração avermelhada proveniente do lado direito, diagnosticando-se infiltração tumoral em vértebras com compressão medular, não sendo possível sua remoção cirúrgica. Na histologia classificou-se o tumor como hemangiossarcoma. Este relato

  1. Physicochemical characterization of two deproteinized bovine xenografts

    Directory of Open Access Journals (Sweden)

    Thais Accorsi-Mendonça


    Full Text Available Calcium phosphate salts, or more specifically hydroxyapatite, are products of great interest in the fields of medical and dental science due to their biocompatibility and osteoconduction property. Deproteinized xenografts are primarily constituted of natural apatites, sintered or not. Variations in the industrial process may affect physicochemical properties and, therefore, the biological outcome. The purpose of this work was to characterize the physical and chemical properties of deproteinized xenogenic biomaterials, Bio-Oss (Geistlich Biomaterials, Wolhuser, Switzerland and Gen-Ox (Baumer S.A., Brazil, widely used as bone grafts. Scanning electron microscopy, infrared region spectroscopy, X-ray diffraction, thermogravimetry and degradation analysis were conducted. The results show that both materials presented porous granules, composed of crystalline hydroxyapatite without apparent presence of other phases. Bio-Oss presented greater dissolution in Tris-HCl than Gen-Ox in the degradation test, possibly due to the low crystallinity and the presence of organic residues. In conclusion, both commercial materials are hydroxyapatite compounds, Bio-Oss being less crystalline than Gen-Ox and, therefore, more prone to degradation.

  2. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. (United States)


    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... 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...

  3. Long-term effectiveness of canine-to-canine bonded flexible spiral wire lingual retainers

    NARCIS (Netherlands)

    Renkema, Anne-Marie; Renkema, Alianne; Bronkhorst, Ewald; Katsaros, Christos


    Introduction: The flexible spiral wire (FSW) canine-to-canine lingual retainer bonded to all 6 anterior teeth is a frequently used type of mandibular fixed retainer. This study aimed to assess the long-term effectiveness of FSW canine-to-canine lingual retainers in maintaining the alignment of the m

  4. Long-term effectiveness of canine-to-canine bonded flexible spiral wire lingual retainers

    NARCIS (Netherlands)

    Renkema, A.M.; Bronkhorst, E.M.; Katsaros, C.


    INTRODUCTION: The flexible spiral wire (FSW) canine-to-canine lingual retainer bonded to all 6 anterior teeth is a frequently used type of mandibular fixed retainer. This study aimed to assess the long-term effectiveness of FSW canine-to-canine lingual retainers in maintaining the alignment of the m

  5. Response of the xenograft endothelium in the concordant xenotransplantation

    Institute of Scientific and Technical Information of China (English)

    Bo Wang; Yi Lu; Cheng'en Pan; Xiaogang Zhang; Hui Li; Kewei Meng; Zheng Wu


    Objective: To investigate the response of the xenograft endothelium in the concordant hamster to rat cardiac xenotransplantation and the mechanism of acute vascular rejection. Methods: The animals were divided into 5 groups randomly: control group,CsA group, splenectomy group, D0 splenectomy+CsA group and D3 splenectomy+CsA group. Hamster heart was heterotopicaly transplanted to rat abdominal cavity. The graft survival was monitored by palpation of the rat abdominal wall. The histological and ultrastructural changes of the xenogafts were investigated. NF-κB and P-selectin expression in the xenograft were detected. Hene Oxigenase-1 and Bcl-2 expression were also detected in the xenografts of different groups. Results: The mean survival time of the xenografts in control group, CsA group, splenectomy group, D0 splenectomy+CsA group and D3 splenectomy+CsA group was 3.4±0.55, 3.8±0.45, 6.4±1.52, 30 and 7.4±1.14 days. The rejected graft showed typical acute vascular rejection in control group, CsA group,splenectomy group and D3 splenectomy+CsA group. Endothelial cells of the rejected xenograft showed dramatic assembly of ribosomes and expansion of the rough endoplasmic reticulum. However, the endothelium of the long-term survived grafts in D0 splenectomy+CsA group showed normal architecture. NF-κB and P-selectin expression were detected in the rejected xenografts. HO-1 expression was observed in the long-term survived xenografts in D0 splenectomy+CsA group. Conclusion: The endothelial cells of the xenograft might be activated during the acute vascular rejection. Expression of HO-1 might inhibit the upregulation of NF-κB and adhesion molecular which decreases the activation of the endothelium of the graft.

  6. Global Conservation of Protein Status between Cell Lines and Xenografts

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    Julian Biau


    Full Text Available Common preclinical models for testing anticancer treatment include cultured human tumor cell lines in monolayer, and xenografts derived from these cell lines in immunodeficient mice. Our goal was to determine how similar the xenografts are compared with their original cell line and to determine whether it is possible to predict the stability of a xenograft model beforehand. We studied a selection of 89 protein markers of interest in 14 human cell cultures and respective subcutaneous xenografts using the reverse-phase protein array technology. We specifically focused on proteins and posttranslational modifications involved in DNA repair, PI3K pathway, apoptosis, tyrosine kinase signaling, stress, cell cycle, MAPK/ERK signaling, SAPK/JNK signaling, NFκB signaling, and adhesion/cytoskeleton. Using hierarchical clustering, most cell culture-xenograft pairs cluster together, suggesting a global conservation of protein signature. Particularly, Akt, NFkB, EGFR, and Vimentin showed very stable protein expression and phosphorylation levels highlighting that 4 of 10 pathways were highly correlated whatever the model. Other proteins were heterogeneously conserved depending on the cell line. Finally, cell line models with low Akt pathway activation and low levels of Vimentin gave rise to more reliable xenograft models. These results may be useful for the extrapolation of cell culture experiments to in vivo models in novel targeted drug discovery.

  7. Podoplanin Expression in Canine Melanoma. (United States)

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari


    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues. PMab-38 could be useful for uncovering the function of PDPN in canine melanomas.

  8. Canine and feline parasitic zoonoses in China. (United States)

    Chen, Jia; Xu, Min-Jun; Zhou, Dong-Hui; Song, Hui-Qun; Wang, Chun-Ren; Zhu, Xing-Quan


    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.

  9. Several early interventions for ectopic maxillary canines.

    Directory of Open Access Journals (Sweden)

    Carlos Astorga


    Full Text Available Maxillary canine impactation is often encountered in orthodontic clinical practice and the aetiology is associated to genetic factors as well as local space factors. If preventive treatment is not started in ectopic maxillary canines, some possible consequences may occur, such as resorption of the roots of the neighboring permanent teeth, cysts, ankylosis and expensive surgical and orthodontic treatment. The aim of this review was to preset several early treatment modalities for ectopic maxillary canines based on recent scientific evidence. Four are the most important: Only extractions intervention, extraction of deciduous canines with cervical pull headgear, active intervention in late mixed dentition and active intervention in early mixed dentition. These different modalities showed a greater increasing the rate of normal eruption of ectopic canines ( 80-97%. The extraction of primary canine alone is still an effective method to prevent canine impactation, whose success rate would be increased if some other method interceptive is added.

  10. Current developments in canine genetics. (United States)

    Marschall, Yvonne; Distl, Ottmar


    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.

  11. Prognostic markers of canine pyometra


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


    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...

  12. Surgical innovations in canine gonadectomy

    NARCIS (Netherlands)

    Van Goethem, Bart


    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

  13. Aspectos epidemiológicos e anatomopatológicos do hemagiossarcoma em cães: 40 casos (1965-2012 Epidemiological and pathological aspects of hemangiosarcoma in dogs: 40 cases (1965-2012

    Directory of Open Access Journals (Sweden)

    Mariana M. Flores


    Full Text Available Os aspectos epidemiológicos e anatomopatológicos de casos de hemangiossarcoma em cães da Região Central do RS foram estudados. Dos casos avaliados (n=40, cães idosos e da raça Pastor Alemão foram nitidamente os mais afetados (72,2% e 20% dos casos, respectivamente, visto que na população total de cães necropsiados nesse mesmo período (n=7.063 essa faixa etária e raça tiveram comparativamente uma prevalência bem mais baixa (14,6% e 10,1% dos casos, respectivamente. Na necropsia (n=40, os tumores ocorreram quase sempre como nódulos (92,5% e, menos frequentemente, como massas (37,5%, e afetaram principalmente: baço (62,5%, pulmão (60%, fígado (52,5%, peritônio (42,5%, rim (37,5%, encéfalo (30%, pleura (25% e coração (22,5%. Hemoperitônio (42,5% e, consequentemente, anemia (22,5% foram vistos com certa frequência. Na histologia (n=25, os hemangiossarcomas eram principalmente bem diferenciados (84%, de baixo grau (64% e com estroma escasso (84%, mas frequentemente (68% havia áreas com células demonstrando algum grau de atipia. Necrose, hemorragia e trombose foram vistos em todos os casos, mas hematopoiese extramedular (28% e proliferação angiomatosa benigna (12% foram achados menos comuns. Na imuno- -histoquímica (n=24, utilizando anticorpo anti-fator de von Willebrand, todos os casos demonstraram marcação de intensidade variável com um padrão citoplasmático finamente granular. Em relação à classificação anatômica, 55% dos hemangiossarcomas foram considerados como multicêntricos, 30% como primários com metástase(s e 15% como solitários. Esse artigo discute esses resultados e propõe, com base em combinações de órgãos afetados, um esquema de separação entre hemangiossarcomas primário com metástase(s e multicêntrico, a fim de tentar homogeneizar a maneira com que patologistas veterinários referem-se a esse neoplasma.Epidemiological and pathological aspects of hemangiosarcoma in dogs from the Central

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

    Directory of Open Access Journals (Sweden)

    Marconato Laura


    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.

  15. Maxillary canine-to-maxillary incisor transposition. (United States)

    Lin, Yng-Tzer J


    Dental transposition is the positional interchange of two adjacent teeth. Canine transpositions are usually accompanied by other dental anomalies, such as: impaction of the incisors; missing teeth; peg-shaped lateral incisors; severe rotation or malposition of adjacent teeth; dilacerations; and malformations. Local pathologic processes, such as tumors, cysts, retained primary canines, and supernumerary teeth, might be responsible for canine transposition. The purpose of this paper was to present a rare case of maxillary canine-to-maxillary incisor transposition in an 8-year-old girl. The patient presented with noneruption of the permanent maxillary left central incisor, and a radiographic examination revealed an impacted dilacerated incisor. The central incisor was extracted because the root was severely dilacerated. At the 3-year follow-up, an oral examination revealed that the canine had transposed to the extraction site. Through orthodontic traction, combined with reshaping of the tooth, the transposed canine was successfully positioned into the incisor position.

  16. Canine and feline parasitic zoonoses in China



    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...

  17. Sewage surveillance reveals the presence of canine GVII norovirus and canine astrovirus in Uruguay. (United States)

    Lizasoain, A; Tort, L F L; García, M; Gómez, M M; Leite, J P G; Miagostovich, M P; Cristina, J; Berois, M; Colina, R; Victoria, Matías


    Canine norovirus (NoV) and astrovirus (AstV) were studied in 20 domestic sewage samples collected in two cities in Uruguay. Four samples were characterized as canine AstV after phylogenetic analysis clustering with strains detected in Italy and Brazil in 2008 and 2012, respectively. One sample was characterized as canine NoV and clustered with a strain detected in Hong Kong and recently classified as GVII. This study shows the occurrence of a canine NoV GVII strain for the first time in the American continent and also warns about possible zoonotic infection, since canine strains were detected in domestic sewage.

  18. Genome Sequence of Canine Herpesvirus.

    Directory of Open Access Journals (Sweden)

    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.

  19. Long-term results of vaginal repairs with and without xenograft reinforcement

    DEFF Research Database (Denmark)

    Mouritsen, Lone; Kronschnabl, M.; Lose, G.


    INTRODUCTION AND HYPOTHESIS: The aim of this paper is to study if xenograft reinforcement of vaginal repair reduces recurrence of prolapse. METHODS: Results 1-5 years after vaginal repair were studied in 41 cases with xenograft and in 82 matched controls without. Symptoms were evaluated by a vali......INTRODUCTION AND HYPOTHESIS: The aim of this paper is to study if xenograft reinforcement of vaginal repair reduces recurrence of prolapse. METHODS: Results 1-5 years after vaginal repair were studied in 41 cases with xenograft and in 82 matched controls without. Symptoms were evaluated......: Recurrence rates defined by POPQ plus symptoms were low compared to literature. Xenograft reinforcement might improve results....

  20. Evaluation of 18-F-fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) as a staging and monitoring tool for dogs with stage-2 splenic hemangiosarcoma – A pilot study (United States)

    Winter, Amber L.; Stuebner, Kathleen; Scott, Ruth; Ober, Christopher P.; Anderson, Kari L.; Feeney, Daniel A.; Vallera, Daniel A.; Koopmeiners, Joseph S.; Modiano, Jaime F.; Froelich, Jerry


    Positron Emission Tomography-Computed Tomography (PET-CT) is routinely used for staging and monitoring of human cancer patients and is becoming increasingly available in veterinary medicine. In this study, 18-fluorodeoxyglucose (18FDG)-PET-CT was used in dogs with naturally occurring splenic hemangiosarcoma (HSA) to assess its utility as a staging and monitoring modality as compared to standard radiography and ultrasonography. Nine dogs with stage-2 HSA underwent 18FDG-PET-CT following splenectomy and prior to commencement of chemotherapy. Routine staging (thoracic radiography and abdominal ultrasonography) was performed prior to 18FDG-PET-CT in all dogs. When abnormalities not identified on routine tests were noted on 18FDG-PET-CT, owners were given the option to repeat a PET-CT following treatment with eBAT. A PET-CT scan was repeated on Day 21 in three dogs. Abnormalities not observed on conventional staging tools, and most consistent with malignant disease based on location, appearance, and outcome, were detected in two dogs and included a right atrial mass and a hepatic nodule, respectively. These lesions were larger and had higher metabolic activity on the second scans. 18FDG-PET-CT has potential to provide important prognostic information and influence treatment recommendations for dogs with stage-2 HSA. Additional studies will be needed to precisely define the value of this imaging tool for staging and therapy monitoring in dogs with this and other cancers. PMID:28222142

  1. 9 CFR 113.306 - Canine Distemper Vaccine. (United States)


    ... 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...

  2. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus. (United States)


    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... canine distemper susceptible dogs (20 vaccinates and 5 controls) shall be used as test animals....

  3. Canine and feline parasitic zoonoses in China

    Directory of Open Access Journals (Sweden)

    Chen Jia


    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.

  4. Exclusion of Complex Paraannular Aortic Abscess With the Freestyle Xenograft. (United States)

    Guihaire, Julien; Kloeckner, Martin; Deleuze, Philippe


    Destructive aortic valve endocarditis is a serious condition that can result in aortoventricular disjunction. The appropriate surgical approach for severe excavating lesions remains a matter of debate. Homografts, prosthetic valves associated with a pericardial patch for annulus repair, and prosthetic valve conduits can be used. We report the technical issue of subcoronary inclusion of the full root Freestyle xenograft for complicated aortic endocarditis extending to the left ventricular outflow tract.

  5. Pathology of Human Pheochromocytoma and Paraganglioma Xenografts in NSG Mice (United States)

    Powers, James F.; Pacak, Karel; Tischler, Arthur S.


    A major impediment to the development of effective treatments for metastatic or unresectable pheochromocytomas and paragangliomas has been the absence of valid models for pre-clinical testing. Attempts to establish cell lines or xenografts from human pheochromocytomas and paragangliomas have previously been unsuccessful. NOD-scid gamma (NSG) mice are a recently developed strain lacking functional B-cells, T-cells and NK cells. We report here that xenografts of primary human paragangliomas will take in NSG mice while maintaining their architectural and immunophenotypic characteristics as expressed in the patients. In contrast to grafts of cell lines and of most common types of primary tumors, the growth rate of grafted paragangliomas is very slow, accurately representing the growth rate of most pheochromocytomas and paragangliomas even in metastases in humans. Although the model is therefore technically challenging, primary patient derived xenografts of paragangliomas in NSG mice provide a potentially valuable new tool that could prove especially valuable for testing treatments aimed at eradicating the small tumor deposits that are often numerous in patients with metastatic paraganglioma. PMID:27709415

  6. Early eruption of permanent canines

    Directory of Open Access Journals (Sweden)

    S Madhu


    Full Text Available Systemic and local factors can modify the eruption time of teeth. Generalized eruption time changes could be due to some systemic diseases like hyperthyroidism, hypophosphatasia, precocious puberty, Proteus syndrome, etc. Localized early eruption of permanent teeth could be due to early extraction of deciduous teeth. Presented here is an extremely rare case of early eruption of permanent canines in a 7-year old female child. Though the number of such cases is very limited, the clinician should poses adequate knowledge and keeps an open eye to identify such cases.

  7. Prognostic markers of canine pyometra

    Directory of Open Access Journals (Sweden)

    M.C. Sant'Anna


    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.

  8. Analysis of the Lipidome of Xenografts Using MALDI-IMS and UHPLC-ESI-QTOF (United States)

    Fernández, Roberto; Lage, Sergio; Abad-García, Beatriz; Barceló-Coblijn, Gwendolyn; Terés, Silvia; López, Daniel H.; Guardiola-Serrano, Francisca; Martín, M. Laura; Escribá, Pablo V.; Fernández, José A.


    Human tumor xenografts in immunodeficient mice are a very popular model to study the development of cancer and to test new drug candidates. Among the parameters analyzed are the variations in the lipid composition, as they are good indicators of changes in the cellular metabolism. Here, we present a study on the distribution of lipids in xenografts of NCI-H1975 human lung cancer cells, using MALDI imaging mass spectrometry and UHPLC-ESI-QTOF. The identification of lipids directly from the tissue by MALDI was aided by the comparison with identification using ESI ionization in lipid extracts from the same xenografts. Lipids belonging to PCs, PIs, SMs, DAG, TAG, PS, PA, and PG classes were identified and their distribution over the xenograft was determined. Three areas were identified in the xenograft, corresponding to cells in different metabolic stages and to a layer of adipose tissue that covers the xenograft.

  9. In vitro chemosensitivity tests on xenografted human melanomas.



    An in vitro chemosensitivity test has been applied to malignant melanoma cells from 5 patients. The tumour cells were first grown as xenografts in immune-suppressed mice, so that the results of the in vitro test could be compared with precise measurements of the sensitivity of the melanoma cells when exposed to chemotherapeutic drugs in vivo in the mouse. The in vitro assay involved exposing the tumour cells to each of 8 drugs, after which cell survival was determined by colony assay in soft ...

  10. Triple bone labeling of canine mandibles

    DEFF Research Database (Denmark)

    Pinholt, E M; Kwon, P H


    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...

  11. [Nonsurgical endodontic treatment of an invaginated canine]. (United States)

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


    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.

  12. Canine babesiosis: from molecular taxonomy to control

    Directory of Open Access Journals (Sweden)

    Irwin Peter J


    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.

  13. Proliferative histiocytic disorders of canine skin. (United States)

    Middleton, D J


    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.

  14. Despre babesioza canină

    Directory of Open Access Journals (Sweden)

    Andrei Nanu


    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.

  15. Biomarkers in canine parvovirus enteritis. (United States)

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


    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.

  16. CANINE: a robotic mine dog (United States)

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


    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.

  17. A new method for rapid Canine retraction

    Directory of Open Access Journals (Sweden)

    "Khavari A


    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.

  18. Canine cytogenetics--from band to basepair. (United States)

    Breen, M


    Humans and dogs have coexisted for thousands of years, during which time we have developed a unique bond, centered on companionship. Along the way, we have developed purebred dog breeds in a manner that has resulted unfortunately in many of them being affected by serious genetic disorders, including cancers. With serendipity and irony the unique genetic architecture of the 21st century genome of Man's best friend may ultimately provide many of the keys to unlock some of nature's most intriguing biological puzzles. Canine cytogenetics has advanced significantly over the past 10 years, spurred on largely by the surge of interest in the dog as a biomedical model for genetic disease and the availability of advanced genomics resources. As such the role of canine cytogenetics has moved rapidly from one that served initially to define the gross genomic organization of the canine genome and provide a reliable means to determine the chromosomal location of individual genes, to one that enabled the assembled sequence of the canine genome to be anchored to the karyotype. Canine cytogenetics now presents the biomedical research community with a means to assist in our search for a greater understanding of how genome architectures altered during speciation and in our search for genes associated with cancers that affect both dogs and humans. The cytogenetics 'toolbox' for the dog is now loaded. This review aims to provide a summary of some of the recent advancements in canine cytogenetics.

  19. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. (United States)


    ..., shall be prepared from virus-bearing cell culture fluids. Only Master Seed Virus which has been... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND...

  20. Results of gal-knockout porcine thymokidney xenografts. (United States)

    Griesemer, A D; Hirakata, A; Shimizu, A; Moran, S; Tena, A; Iwaki, H; Ishikawa, Y; Schule, P; Arn, J S; Robson, S C; Fishman, J A; Sykes, M; Sachs, D H; Yamada, K


    Clinical transplantation for the treatment of end-stage organ disease is limited by a shortage of donor organs. Successful xenotransplantation could immediately overcome this limitation. The development of homozygous alpha1,3-galactosyltransferase knockout (GalT-KO) pigs removed hyperacute rejection as the major immunologic hurdle to xenotransplantation. Nevertheless, GalT-KO organs stimulate robust immunologic responses that are not prevented by immunosuppressive drugs. Murine studies show that recipient thymopoiesis in thymic xenografts induces xenotolerance. We transplanted life-supporting composite thymokidneys (composite thymus and kidneys) prepared in GalT-KO miniature swine to baboons in an attempt to induce tolerance in a preclinical xenotransplant model. Here, we report the results of seven xenogenic thymokidney transplants using a steroid-free immunosuppressive regimen that eliminated whole-body irradiation in all but one recipient. The regimen resulted in average recipient survival of over 50 days. This was associated with donor-specific unresponsiveness in vitro and early baboon thymopoiesis in the porcine thymus tissue of these grafts, suggesting the development of T-cell tolerance. The kidney grafts had no signs of cellular infiltration or deposition of IgG, and no grafts were lost due to rejection. These results show that xenogeneic thymus transplantation can support early primate thymopoiesis, which in turn may induce T-cell tolerance to solid organ xenografts.

  1. Reproducibility of Differential Proteomic Technologies in CPTAC Fractionated Xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Tabb, David L.; Wang, Xia; Carr, Steven A.; Clauser, Karl R.; Mertins, Philipp; Chambers, Matthew C.; Holman, Jerry D.; Wang, Jing; Zhang, Bing; Zimmerman, Lisa J.; Chen, Xian; Gunawardena, Harsha P.; Davies, Sherri R.; Ellis, Matthew J. C.; Li, Shunqiang; Townsend, R. Reid; Boja, Emily S.; Ketchum, Karen A.; Kinsinger, Christopher R.; Mesri, Mehdi; Rodriguez, Henry; Liu, Tao; Kim, Sangtae; McDermott, Jason E.; Payne, Samuel H.; Petyuk, Vladislav A.; Rodland, Karin D.; Smith, Richard D.; Yang, Feng; Chan, Daniel W.; Zhang, Bai; Zhang, Hui; Zhang, Zhen; Zhou, Jian-Ying; Liebler, Daniel C.


    The NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) employed a pair of reference xenograft proteomes for initial platform validation and ongoing quality control of its data collection for The Cancer Genome Atlas (TCGA) tumors. These two xenografts, representing basal and luminal-B human breast cancer, were fractionated and analyzed on six mass spectrometers in a total of 46 replicates divided between iTRAQ and label-free technologies, spanning a total of 1095 LC-MS/MS experiments. These data represent a unique opportunity to evaluate the stability of proteomic differentiation by mass spectrometry over many months of time for individual instruments or across instruments running dissimilar workflows. We evaluated iTRAQ reporter ions, label-free spectral counts, and label-free extracted ion chromatograms as strategies for data interpretation. From these assessments we found that differential genes from a single replicate were confirmed by other replicates on the same instrument from 61-93% of the time. When comparing across different instruments and quantitative technologies, differential genes were reproduced by other data sets from 67-99% of the time. Projecting gene differences to biological pathways and networks increased the similarities. These overlaps send an encouraging message about the maturity of technologies for proteomic differentiation.

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

    Directory of Open Access Journals (Sweden)

    Praveen Mehrotra


    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.

  3. Comparative studies of canine colipase and lipases from bovine, porcine, canine, human and rat pancreases. (United States)

    Lee, P C


    1. Colipase was purified from canine pancreatic juice and found to have certain specificity in its reaction with various pancreatic lipases. 2. This colipase will stimulate the lipolytic activities of lipases isolated from canine, bovine and porcine pancreas but not lipases from a fungus, or from human and rat pancreases. 3. Characterization of these lipases showed (a) the molecular dimension of rat lipase is very different from the other lipases; (b) the pIs of canine, porcine and bovine lipases are almost identical but different from the pIs of rat, human and Candida (a fungus) lipases; and (c) the antiserum prepared against canine lipase will also react with lipases from human, hog and cow pancreases but not with rat and Candida lipases. 4. These physical differences can explain partly the difference in reaction between the various lipases and the canine colipase.

  4. Hypoxia-regulated gene expression explains differences between melanoma cell line-derived xenografts and patient-derived xenografts. (United States)

    Bhadury, Joydeep; Einarsdottir, Berglind O; Podraza, Agnieszka; Bagge, Roger Olofsson; Stierner, Ulrika; Ny, Lars; Dávila López, Marcela; Nilsson, Jonas A


    Cell line-derived xenografts (CDXs) are an integral part of drug efficacy testing during development of new pharmaceuticals against cancer but their accuracy in predicting clinical responses in patients have been debated. Patient-derived xenografts (PDXs) are thought to be more useful for predictive biomarker identification for targeted therapies, including in metastatic melanoma, due to their similarities to human disease. Here, tumor biopsies from fifteen patients and ten widely-used melanoma cell lines were transplanted into immunocompromised mice to generate PDXs and CDXs, respectively. Gene expression profiles generated from the tumors of these PDXs and CDXs clustered into distinct groups, despite similar mutational signatures. Hypoxia-induced gene signatures and overexpression of the hypoxia-regulated miRNA hsa-miR-210 characterized CDXs. Inhibition of hsa-miR-210 with decoys had little phenotypic effect in vitro but reduced sensitivity to MEK1/2 inhibition in vivo, suggesting down-regulation of this miRNA could result in development of resistance to MEK inhibitors.

  5. Complications of misdiagnosis of maxillary canine ectopic eruption. (United States)

    Garib, Daniela Gamba; Janson, Guilherme; Baldo, Taiana de Oliveira; dos Santos, Patrícia Bittencourt Dutra


    Ectopic eruption of maxillary canines can be associated with root resorption of adjacent teeth. This case report describes and discusses an interesting case of a 15-year-old girl with a Class III malocclusion and an impacted maxillary canine. Because of the unfavorable position of the ectopic canine and the severe root resorption of the maxillary left central and lateral incisors, the treatment options included extraction of the maxillary permanent canines. The mandibular first premolars were extracted to compensate for the Class III malocclusion. A panoramic radiograph taken earlier in the mixed dentition already indicated a possible eruption disturbance of the maxillary left permanent canine. The importance of early diagnosis of maxillary canine ectopic eruption is highlighted in this case report. The early identification of radiographic signs of an ectopic pathway of eruption should be followed by deciduous canine extraction to prevent canine retention and maxillary incisor root resorption.

  6. Sexual Dimorphism in Human Mandibular Canine Teeth: A Radiomorphometric Study

    Directory of Open Access Journals (Sweden)

    K S Nagesh


    Conclusion: The present study establishes a statistically significant sexual dimorphism in mandibular canines- It can be concluded that the standard mandibular canine index is a quick and easy method for sex determination.

  7. Serological detection of infection with canine distemper virus, canine parvovirus and canine adenovirus in communal dogs from Zimbabwe. (United States)

    McRee, Anna; Wilkes, Rebecca P; Dawson, Jessica; Parry, Roger; Foggin, Chris; Adams, Hayley; Odoi, Agricola; Kennedy, Melissa A


    Domestic dogs are common amongst communities in sub-Saharan Africa and may serve as important reservoirs for infectious agents that may cause diseases in wildlife. Two agents of concern are canine parvovirus (CPV) and canine distemper virus (CDV), which may infect and cause disease in large carnivore species such as African wild dogs and African lions, respectively. The impact of domestic dogs and their diseases on wildlife conservation is increasing in Zimbabwe, necessitating thorough assessment and implementation of control measures. In this study, domestic dogs in north-western Zimbabwe were evaluated for antibodies to CDV, CPV, and canine adenovirus (CAV). These dogs were communal and had no vaccination history. Two hundred and twenty-five blood samples were collected and tested using a commercial enzyme-linked immunosorbent assay (ELISA) for antibodies to CPV, CDV, and CAV. Of these dogs, 75 (34%) had detectable antibodies to CDV, whilst 191 (84%) had antibodies to CPV. Antibodies to canine adenovirus were present in 28 (13%) dogs. Canine parvovirus had high prevalence in all six geographic areas tested. These results indicate that CPV is circulating widely amongst domestic dogs in the region. In addition, CDV is present at high levels. Both pathogens can infect wildlife species. Efforts for conservation of large carnivores in Zimbabwe must address the role of domestic dogs in disease transmission.

  8. Serological detection of infection with canine distemper virus, canine parvovirus and canine adenovirus in communal dogs from Zimbabwe

    Directory of Open Access Journals (Sweden)

    Anna McRee


    Full Text Available Domestic dogs are common amongst communities in sub-Saharan Africa and may serve as important reservoirs for infectious agents that may cause diseases in wildlife. Two agents of concern are canine parvovirus (CPV and canine distemper virus (CDV, which may infect and cause disease in large carnivore species such as African wild dogs and African lions, respectively. The impact of domestic dogs and their diseases on wildlife conservation is increasing in Zimbabwe, necessitating thorough assessment and implementation of control measures. In this study, domestic dogs in north-western Zimbabwe were evaluated for antibodies to CDV, CPV, and canine adenovirus (CAV. These dogs were communal and had no vaccination history. Two hundred and twenty-five blood samples were collected and tested using a commercial enzyme-linked immunosorbent assay (ELISA for antibodies to CPV, CDV, and CAV. Of these dogs, 75 (34% had detectable antibodies to CDV, whilst 191 (84% had antibodies to CPV. Antibodies to canine adenovirus were present in 28 (13% dogs. Canine parvovirus had high prevalence in all six geographic areas tested. These results indicate that CPV is circulating widely amongst domestic dogs in the region. In addition, CDV is present at high levels. Both pathogens can infect wildlife species. Efforts for conservation of large carnivores in Zimbabwe must address the role of domestic dogs in disease transmission.

  9. Imaging Axl expression in pancreatic and prostate cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Nimmagadda, Sridhar, E-mail: [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21287 (United States); Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287 (United States); Pullambhatla, Mrudula; Lisok, Ala [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21287 (United States); Hu, Chaoxin [Department of Pathology, Johns Hopkins University, Baltimore, MD 21287 (United States); Maitra, Anirban [Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287 (United States); Department of Pathology, Johns Hopkins University, Baltimore, MD 21287 (United States); Pomper, Martin G, E-mail: [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21287 (United States); Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287 (United States)


    Highlights: •Axl is overexpressed in a variety of cancers. •Axl overexpression confers invasive phenotype. •Axl imaging would be useful for therapeutic guidance and monitoring. •Axl expression imaging is demonstrated in pancreatic and prostate cancer xenografts. •Graded levels of Axl expression imaging is feasible. -- Abstract: The receptor tyrosine kinase Axl is overexpressed in and leads to patient morbidity and mortality in a variety of cancers. Axl–Gas6 interactions are critical for tumor growth, angiogenesis and metastasis. The goal of this study was to investigate the feasibility of imaging graded levels of Axl expression in tumors using a radiolabeled antibody. We radiolabeled anti-human Axl (Axl mAb) and control IgG1 antibodies with {sup 125}I with high specific radioactivity and radiochemical purity, resulting in an immunoreactive fraction suitable for in vivo studies. Radiolabeled antibodies were investigated in severe combined immunodeficient mice harboring subcutaneous CFPAC (Axl{sup high}) and Panc1 (Axl{sup low}) pancreatic cancer xenografts by ex vivo biodistribution and imaging. Based on these results, the specificity of [{sup 125}I]Axl mAb was also validated in mice harboring orthotopic Panc1 or CFPAC tumors and in mice harboring subcutaneous 22Rv1 (Axl{sup low}) or DU145 (Axl{sup high}) prostate tumors by ex vivo biodistribution and imaging studies at 72 h post-injection of the antibody. Both imaging and biodistribution studies demonstrated specific and persistent accumulation of [{sup 125}I]Axl mAb in Axl{sup high} (CFPAC and DU145) expression tumors compared to the Axl{sup low} (Panc1 and 22Rv1) expression tumors. Axl expression in these tumors was further confirmed by immunohistochemical studies. No difference in the uptake of radioactivity was observed between the control [{sup 125}I]IgG1 antibody in the Axl{sup high} and Axl{sup low} expression tumors. These data demonstrate the feasibility of imaging Axl expression in pancreatic

  10. Implantation of decellularized small-caliber vascular xenografts with and without surface heparin treatment

    NARCIS (Netherlands)

    Wang, Xue-Ning; Chen, Chang-Zhi; Yang, Min; Gu, Y. John


    Heparin treatment of decellularized xenografts has been reported to reduce graft thrombogenicity. However, little is known about the in vivo comparison of heparin-treated with non-heparin-treated xenografts, especially for small-caliber vascular implants. We implanted either a heparin-treated or a n

  11. 9 CFR 113.316 - Canine Parainfluenza Vaccine. (United States)


    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Parainfluenza Vaccine. 113.316... Virus Vaccines § 113.316 Canine Parainfluenza Vaccine. Canine Parainfluenza Vaccine shall be prepared... immunogenic shall be used for preparing seeds for vaccine production. All serials of vaccine shall be...

  12. Human airway xenograft models of epithelial cell regeneration

    Directory of Open Access Journals (Sweden)

    Puchelle Edith


    Full Text Available Abstract Regeneration and restoration of the airway epithelium after mechanical, viral or bacterial injury have a determinant role in the evolution of numerous respiratory diseases such as chronic bronchitis, asthma and cystic fibrosis. The study in vivo of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to restore a functional respiratory epithelium after several weeks. Recently, human tracheal xenografts have been developed in immunodeficient severe combined immunodeficiency (SCID and nude mice. In this review we recall that human airway cells implanted in such conditioned host grafts can regenerate a well-differentiated and functional human epithelium; we stress the interest in these humanized mice in assaying candidate progenitor and stem cells of the human airway mucosa.

  13. Retinal progenitor cell xenografts to the pig retina

    DEFF Research Database (Denmark)

    Warfvinge, Karin; Kiilgaard, Jens Folke; Klassen, Henry;


    We evaluated the host response to murine retinal progenitor cells (RPCs) following transplantation to the subretinal space (SRS) of the pig. RPCs from GFP mice were transplanted subretinally in 18 nonimmunosuppressed normal or laser-treated pigs. Evaluation of the SRS was performed on hematoxylin...... inflammatory cells in the choroid near the transplantation site. Large choroidal infiltrates were evident at 2-5 weeks. Serum from naive and RPC-xenografted pigs contained significant levels of preformed IgG and IgM antibodies against murine antigens. Xenogeneic RPCs transplanted to the porcine SRS induced...... mononuclear infiltration in the choroid with graft rejection occurring over 2-5 weeks. Serum analysis confirmed that mice and pigs are discordant species; however, a cell-mediated acute mechanism appears to be responsible, rather than an antibody-mediated rejection....

  14. Booster effect of canine distemper, canine parvovirus infection and infectious canine hepatitis combination vaccine in domesticated adult dogs. (United States)

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Orito, Kensuke; Lynch, Jonathan; Tsuchiya, Ryo; Sahara, Hiroeki


    Domesticated adult dogs with antibody titer classified as below 'high' to one or more of canine distemper virus (CDV), canine parvovirus type-2 (CPV-2) and canine adenovirus type-1 (CAdV-1) were then given an additional inoculation, and the effectiveness of this booster evaluated 2 months later. Consequently, CDV and CAdV-1 antibody titer experienced a significant increase, but the same effect was not observed in the antibody titer of CPV-2. These findings suggest that with additional inoculation, a booster effect may be expected in increasing antibody titers for CDV and CAdV-1, but it is unlikely to give an increase in CPV-2 antibody titer.

  15. Antibody titers for canine parvovirus type-2, canine distemper virus, and canine adenovirus type-1 in adult household dogs. (United States)

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Orito, Kensuke; Lynch, Jonathan; Sahara, Hiroeki


    Serum antibody titers for canine parvovirus type-2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type-1 (CAV-1) were investigated in 1031 healthy adult household dogs (2 to 18 years old) given an annual inoculation in the previous 11 to 13 months. The number of dogs retaining significant titers of antibodies against CPV-2, CDV, and CAV-1 were 888 (86%), 744 (72%), and 732 (71%), respectively. There were no differences between males and females in antibody titers against the 3 viruses. Antibody titer for CPV-2 was significantly higher in younger dogs than in older dogs, CDV antibody was significantly higher in older dogs than in younger dogs, and CAV titer was not associated with age.

  16. Canine pyometra: What is new? (United States)

    Hagman, R


    Pyometra is a common disease in countries where elective spaying is not routinely performed. Hormonal and bacterial factors are fundamental in the pathogenesis of the disease, which manifests itself as a potentially life-threatening bacterial infection of the uterus. Surgical ovariohysterectomy is the safest and most effective treatment for pyometra, and it has recently been shown that laparoscopically assisted methods for surgical treatment are feasible to use in selected cases. New protocols for improved medical treatment alternatives have also been tested with promising results. To be able to predict outcome and presence of complications early would be valuable in clinical practice for optimizing therapy and increasing survival. Results of commonly investigated clinical and laboratory investigations have been shown to be useful as predictive markers, with leucopenia being associated with increased risk of peritonitis as well as prolonged post-operative hospitalization after surgical treatment. A cage-side rapid and cost-effective diagnostic test would be highly valuable in clinical practice, and detection of pyometra-specific upregulated genes in the uterus and the corresponding products is a potential start in identifying novel markers suitable for such as test. The focus of the present review is to highlight recent findings on pathogenesis, prediction of outcome, diagnosis and treatment. Additionally, central research questions and suggestions for future investigations about several aspects of canine pyometra will be addressed.

  17. Composite mandibular allografts in canines

    Institute of Scientific and Technical Information of China (English)


    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.

  18. Canine mammary tumors - clinical survey

    Directory of Open Access Journals (Sweden)

    Elena Atanaskova Petrov


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

  19. Overexpression of vimentin in canine prostatic carcinoma

    DEFF Research Database (Denmark)

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


    Canine prostatic tumours exhibit similarities to those of man and may represent a useful model system to explore the mechanisms of cancer progression. Tumour progression to malignancy requires a change from an epithelial phenotype to a fibroblastic or mesenchymal phenotype. Vimentin expression...... 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...... that the acquisition of the epithelial-mesenchymal transition phenotype in canine prostatic carcinoma may be characterized by the presence of mesenchymal intermediate filament (vimentin) that could lead to a higher likelihood of metastasis....

  20. Proteins of the canine seminal plasma

    Directory of Open Access Journals (Sweden)

    Annice Aquino-Cortez


    Full Text Available ABSTRACT: Studies have been performed to identify the proteins present in canine seminal plasma (SP and relate them to sperm quality as well as to discover molecular markers of reproductive tract diseases. There is evidence that heparin-binding proteins, zinc-binding proteins, and lactoferrin as well as the matrix metalloproteinase, superoxide dismutase, catalase, and glutathione peroxidase enzymes are associated with canine sperm quality. Other studies indicate that prolactin and enzymes like arginine esterase, acid phosphatase, and alkaline phosphatase could be successfully used as biomarkers of reproductive disorders. Thus, the present literature review aims to address aspects related to proteins of the canine SP, their influence on fertility, and their importance as biomarkers of reproductive disorders.

  1. Early and unusual incisor resorption due to impacted maxillary canines. (United States)

    Otto, Ronald L


    A very early and severe case of maxillary incisor resorption caused by impacted canines is reported. An estimated 50,000 cases of ectopic eruption and impaction of maxillary canines occur each year in the United States. Although incisor resorption due to ectopically positioned permanent maxillary canines can be swift, silent, and devastating, an effective protocol has been developed for early detection and management of this condition. Palpation and, if indicated, radiographic evaluation are combined with primary canine removal in selected cases. These strategies--particularly when used early--can prevent the vast majority of palatally impacted maxillary canines and the potentially devastating resorption of adjacent incisors.


    Directory of Open Access Journals (Sweden)



    Full Text Available : Impacted teeth are those which are not predictable and do not erupt absolutely based on clinical and radiographic assessment. Certain impactions can be complicated and the outcome unpredictable if the tooth is positioned unfavourably either horizontally or vertically in the alveolar bone. Presence of canines buccally, palatally or lingually can be seen using various diagnostic methods. Factors that interfere with its development and eruption have influence on aesthetics’, function and stability. A detailed understanding of the management of impacted teeth is essential for a stable and aesthetic result. So, we put forth the most common procedures which can be carried out by general dentists in managing impacted maxillary canines.

  3. Medical Treatment of Primary Canine Glaucoma. (United States)

    Alario, Anthony F; Strong, Travis D; Pizzirani, Stefano


    Glaucoma is a painful and often blinding group of ocular diseases for which there is no cure. Although the definition of glaucoma is rapidly evolving, elevated intraocular pressure (IOP) remains the most consistent risk factor of glaucoma in the canine patient. Therapy should be aimed at neuroprotection. The mainstay of therapy focuses on reducing IOP and maintaining a visual and comfortable eye. This article discusses the most current ocular hypotensive agents, focusing on their basic pharmacology, efficacy at lowering IOP, and recommended use in the treatment of idiopathic canine glaucoma.

  4. A Study of Transmigrated Canine in an Indian Population. (United States)

    Sharma, Gaurav; Nagpal, Archna


    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.

  5. A Study of Transmigrated Canine in an Indian Population (United States)

    Sharma, Gaurav; Nagpal, Archna


    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

  6. Derivation of sperm from xenografted testis cells and tissues of the peccary (Tayassu tajacu). (United States)

    Campos-Junior, Paulo Henrique Almeida; Costa, Guilherme Mattos Jardim; Avelar, Gleide Fernandes; Lacerda, Samyra Maria Santos Nassif; da Costa, Nathália Nogueira; Ohashi, Otávio Mitio; Miranda, Moysés dos Santos; Barcelos, Lucíola Silva; Jorge, Erika Cristina; Guimarães, Diva Anelie; de França, Luiz Renato


    Because the collared peccary (Tayassu tajacu) has a peculiar Leydig cell cytoarchitecture, this species represents a unique mammalian model for investigating testis function. Taking advantage of the well-established and very useful testis xenograft technique, in the present study, testis tissue and testis cell suspensions from immature collared peccaries (n=4; 3 months old) were xenografted in SCID mice (n=48) and evaluated at 2, 4, 6, and 8 months after grafting. Complete spermatogenesis was observed at 6 and 8 months after testis tissue xenografting. However, probably due to de novo testis morphogenesis and low androgen secretion, functionally evaluated by the seminal vesicle weight, a delay in spermatogenesis progression was observed in the testis cell suspension xenografts, with the production of fertile sperm only at 8 months after grafting. Importantly, demonstrating that the peculiar testicular cytoarchitecture of the collared peccary is intrinsically programmed, the unique Leydig cell arrangement observed in this species was re-established after de novo testis morphogenesis. The sperm collected from the xenografts resulted in diploid embryos that expressed the paternally imprinted gene NNAT after ICSI. The present study is the first to demonstrate complete spermatogenesis with the production of fertile sperm from testis cell suspension xenografts in a wild mammalian species. Therefore, due to its unique testicular cytoarchitecture, xenograft techniques, particularly testis cell suspensions, may represent a new and very promising approach to evaluate testis morphogenesis and to investigate spermatogonial stem cell physiology and niche in the collared peccary.

  7. Effects of Hypericum perforatum on the healing of xenografts: a histomorphometric study in rabbits. (United States)

    Damlar, I; Arpağ, O F; Tatli, U; Altan, A


    The aim of this study was to investigate effects of the Hypericum perforatum (St John's Wort) on bone healing in rabbit calvarium. Ten male New Zealand rabbits each had three bicortical defects made in the calvarial bones, which were filled with xenograft, xenograft+H perforatum oil extract, and autogenous graft. Four weeks postoperatively all rabbits were killed and the bony defects examined histomorphometrically. Tissue compartments including new bone (p<0.001), marrow space (p<0.001), and residual bone grafts (p=0.014) differed significantly among groups (p=0.00?). The volume of residual graft was significantly decreased in the xenograft/H perforatum group compared with those with xenografts alone (p=0.0147). The differences in microarchitectural variables of de novo bone formation were also significant (trabecular thickness (p<0.001), trabecular width (p<0.001), trabecular separation (p=0.001). There were no significant differences in node:terminus ratio between the xenograft/H perforatum group and the other two groups. However, the difference in node:terminus ratio between the autogenous graft and xenograft group was significant (p=0.001) Oil extracts of H perforatum improved bony healing in defects filled with bovine-derived xenografts.

  8. Immune-mediated canine and feline keratitis. (United States)

    Andrew, Stacy E


    Although the normal cornea is devoid of vasculature and lymphatics, there are still several immune-mediated corneal conditions that can occur in dogs and cats. An overview of corneal immunology is presented. Diseases of dogs, including chronic superficial keratitis, superficial punctate keratitis, and canine adenovirus endotheliitis, as well as feline diseases, including eosinophilic keratitis and herpesvirus-related conditions, are discussed.

  9. Canine retraction with J hook headgear. (United States)

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


    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.

  10. A novel bocavirus in canine liver

    Directory of Open Access Journals (Sweden)

    Li Linlin


    Full Text Available Abstract Background Bocaviruses are classified as a genus within the Parvoviridae family of single-stranded DNA viruses and are pathogenic in some mammalian species. Two species have been previously reported in dogs, minute virus of canines (MVC, associated with neonatal diseases and fertility disorders; and Canine bocavirus (CBoV, associated with respiratory disease. Findings In this study using deep sequencing of enriched viral particles from the liver of a dog with severe hemorrhagic gastroenteritis, necrotizing vasculitis, granulomatous lymphadenitis and anuric renal failure, we identified and characterized a novel bocavirus we named Canine bocavirus 3 (CnBoV3. The three major ORFs of CnBoV3 (NS1, NP1 and VP1 shared less than 60% aa identity with those of other bocaviruses qualifying it as a novel species based on ICTV criteria. Inverse PCR showed the presence of concatemerized or circular forms of the genome in liver. Conclusions We genetically characterized a bocavirus in a dog liver that is highly distinct from prior canine bocaviruses found in respiratory and fecal samples. Its role in this animal’s complex disease remains to be determined.

  11. Efficacy of Scabisol against Canine Demodecosis

    Directory of Open Access Journals (Sweden)

    A.M. Bodkhe

    Full Text Available In the present study scabisol containing precipitated sulphur was tried in 10 dogs suffering from Canine demodecosis. The improvement was observed within 72 hours of treatment, and complete recovery was noticed after three consecutive treatments. [Veterinary World 2008; 1(7.000: 211-211

  12. Cardiac involvement in canine babesiosis : review article

    Directory of Open Access Journals (Sweden)

    R.G. Lobetti


    Full Text Available Cardiac dysfunction in canine babesiosis has traditionally been regarded as a rare complication, with the majority of lesions reported as incidental findings at post-mortem examination. Recent studies have, however, demonstrated cardiac lesions in canine babesiosis. Cardiac troponins, especially troponin I, are sensitive markers of myocardial injury in canine babesiosis, and the magnitude of elevation of plasma troponin I concentrations appears to be proportional to the severity of the disease. ECG changes in babesiosis are similar to the pattern described for myocarditis and myocardial ischaemia and together with histopathological findings indicate that the heart suffers from the same pathological processes described in other organs in canine babesiosis, namely inflammation and hypoxia. The clinical application of the ECG appears to be limited and thus cardiovascular assessment should be based on functional monitoring rather than an ECG tracing. On cardiac histopathology from dogs that succumbed to babesiosis, haemorrhage, necrosis, inflammation and fibrin microthrombi in the myocardium were documented, all of which would have resulted in ECG changes and elevations in cardiac troponin. Myocardial damage causes left ventricular failure, which will result in hypotension and an expansion of the plasma volume due to homeostatic mechanisms.

  13. Canine notoedric mange: a case report. (United States)

    Leone, Federico


    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.

  14. Medical dissolution of canine struvite uroliths. (United States)

    Osborne, C A; Polzin, D J; Kruger, J M; Abdullahi, S U; Leininger, J R; Griffith, D P


    Medical therapy is an effective method of canine struvite urolith dissolution. Recommendations include (1) eradication or control of urinary tract infection (if present), (2) use of calculolytic diets, and (3) administration of urease inhibitors to patients with persistent urinary tract infection caused by urease-producing microbes.

  15. Canine specific ELISA for coagulation factor VII

    DEFF Research Database (Denmark)

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


    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...

  16. Canine distemper outbreak in rhesus monkeys, China. (United States)

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


    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.

  17. Ineffective photodynamic therapy (PDT) in a poorly vascularized xenograft model. (United States)

    White, L.; Gomer, C. J.; Doiron, D. R.; Szirth, B. C.


    Haematoporphyrin derivative (HPD) photodynamic therapy (PDT) may have clinical application in the management of patients with retinoblastoma. Heterotransplantation of retinoblastoma cells into the anterior chamber of the nude mouse eye and the subsequent growth of small tumour masses has provided a model for evaluation of various therapeutic modalities. Ninety-four evaluable xenograft tumours in 54 nude mice were randomized to receive one of the following treatments: cyclophosphamide (CPM) alone, HPD-PDT alone, CPM followed by HPD-PDT, HPD-PDT followed by CPM, or saline control. Responses were demonstrated after CPM treatment in all three relevant groups. However, HPD-PDT was found to be ineffective either alone or as a contributor in the double modality treatment groups. The small tumour masses treated can be demonstrated histologically to be avascular. It is proposed that although the same retinoblastoma cells in different circumstances are responsive to HPD-PDT, no clinical response is demonstrable utilizing this model, due to the absence of tumor vascularity. Images Figure 1 Figure 2 PMID:3395551

  18. Deciduous canine and permanent lateral incisor differential root resorption. (United States)

    Davies, K R; Schneider, G B; Southard, T E; Hillis, S L; Wertz, P W; Finkelstein, M; Hogan, M M


    When a permanent maxillary canine erupts apical to the permanent lateral incisor and the deciduous canine, resorption typically takes place only on the deciduous canine root. An understanding of this differential resorption could provide insight into the reasons for excessive iatrogenic root resorption during orthodontic tooth movement. The purpose of the present study was to examine the response of roots of permanent lateral incisors and deciduous canines to simulated resorption, and to acid and enzyme attack, reflecting the physiologic environment of an erupting permanent canine. Groups of maxillary permanent lateral incisor and deciduous canine roots were exposed to 5 combinations of Ten Cate demineralizing solution, Ten Cate demineralizing solution with EDTA, and a Type I collagenase solution. Sections of the roots were examined under a polarized light microscope. Analysis of variation of the resulting root lesions demonstrated that the lesion depths for deciduous canines were greater than those for permanent lateral incisors when averaged across 4 of the conditions (F(1,24) = 7.49, P =.0115). On average, deciduous canine roots demonstrated lesions 10% deeper than did permanent lateral incisor roots. We concluded that when deciduous canine and permanent lateral incisor roots are subjected to acid and enzyme attack, reflecting the physiologic environment of an erupting permanent canine, significantly deeper demineralized lesions are seen in the deciduous roots compared with the permanent roots. This finding may partially explain the differential root resorption during permanent tooth eruption.

  19. A comprehensive characterization of cell cultures and xenografts derived from a human verrucous penile carcinoma

    DEFF Research Database (Denmark)

    Muñoz, Juan J; Drigo, Sandra A; Kuasne, Hellen;


    , and cultivated in KSFM/DF12 medium. Cell cultures were evaluated at passage 5 (P5) using migration and invasion assays and were serially propagated, in vivo, in BALB/c nude mice until passage 3 (X1-X3). Immunophenotypic characterization of cultures and xenografts was performed. Genomic (CytoScan HD, Affymetrix...... xenograft origin. Cell cultures and xenografts retained the genomic alterations present in the parental tumor. Compared to VSCC, differentially expressed transcripts detected in all experimental conditions were associated with cellular morphology, movement, and metabolism and organization pathways......This study aimed to establish and characterize primary cell cultures and xenografts derived from penile carcinoma (PeCa) in order to provide experimental models for cellular processes and efficacy of new treatments. A verrucous squamous cell carcinoma (VSCC) was macrodissected, dissociated...

  20. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

    Directory of Open Access Journals (Sweden)

    Sergey V. Tokalov


    Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

  1. Gene Expression Profiles Can Predict Panitumumab Monotherapy Responsiveness in Human Tumor Xenograft Models

    Directory of Open Access Journals (Sweden)

    Michael J. Boedigheimer


    Conclusion A model was constructed from microarray data that prospectively predict responsiveness to panitumumab in xenograft models. This approach may help identify patients, independent of disease origin, likely to benefit from panitumumab.

  2. Xenografting as a Tool to Preserve Endangered Species: Outcomes and Challenges in Model Systems

    Directory of Open Access Journals (Sweden)

    Paula C. Mota


    Full Text Available The use of testis tissue xenografting as a valuable tool to rescue endangered and genetically valuable individuals that die young or otherwise fail to produce sperm has been the subject of much interest. Although the technique has been successfully applied to a wide variety of species, little is known about what determines the outcome. Furthermore, to improve the applicability of xenografting, new methods to preserve and transport testis tissue from valuable animals are emerging. However, one major issue remains: the application of xenografting implies the development of subsequent ART techniques to produce offspring from the recovered material. This paper focuses on these three aspects of testis tissue xenografting as a tool for rescuing endangered and valuable genetic pools.

  3. Survivin expression in canine epidermis and in canine and human cutaneous squamous cell carcinomas. (United States)

    Bongiovanni, Laura; Colombi, Isabella; Fortunato, Carmine; Della Salda, Leonardo


    Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is ubiquitously expressed during tissue development, undetectable in most normal tissues, but re-expressed in most cancers, including skin malignancies. Expression of survivin was evaluated retrospectively in 19 canine cutaneous squamous cell carcinomas (SCCs; one in situ; 16 well differentiated; one invasive, one lymph node metastasis) and 19 well differentiated SCCs from human beings. Seven specimens of normal canine skin were included. Immunohistochemical expression of full-length survivin was determined using a commercially available antibody. In addition, apoptotic rate [Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labelling index (TUNEL) index] and mitotic index (MI), counting mitoses in 10 high power fields (HPF), were determined. Scattered survivin positive nuclei were identified in the epidermal basal cell layer of normal canine skin. Nuclear survivin expression was identified in 18 of 19 human and in all canine SCCs, mainly along the base of the tumour cell population. Cytoplasmic survivin expression was rarely observed in human SCCs and in 84.2% of canine SCCs. The TUNEL index ranged from 0.1 to 2.6 in human beings and from 7.5 to 69.4 in dogs, while MIs ranged from 0 to 4 in human beings and dogs. No correlation was found between survivin expression and apoptotic or mitotic rates. Canine and human tumours showed similar nuclear survivin expression, indicating similar functions of the molecule. We demonstrated survivin expression in normal adult canine epidermis. Increased nuclear survivin expression in pre-neoplastic and neoplastic lesions demonstrates a possible association of survivin with development of SCCs in human beings and dogs.

  4. Establishment and Its Biological Characteristics of Patient-derived Lung Cancer Xenograft Modelse

    Directory of Open Access Journals (Sweden)

    Ying ZHUO


    Full Text Available Background and objective With the ongoing need to improve therapy for lung cancer, there has been an increasing interest in the development of reliable preclinical models to test novel therapeutics. The aim of this study is to establish a patient-derived lung cancer xenograft model in mice and to observe the biological characteristics of xenografts. Methods Surgically resectected tumor specimens from patients with lung cancer were implanted in the subcutaneous layer of the NOD/SCID mice. Cancer specimens of percutaneous lung biopsy by CT fluoroscopy were implanted into the subrenal capsule of nude mouse. The subcutaneous carcinoma was surgically removed when it grew to approximately 1.0 cm in diameter, and then re-transplanted into new nude mice. The growth process of transplanted tumor was observed. Expression of CEA, cytokeratin, and Ki67 were detected by immunohistochemistry. Mutations in the exons 18-21 of EGFR and exons 12,59 of K-ras of primary and xenograft tumors were examined. The cell cycle of xenograft tumor cells was analyzed by flow cytometry. Results Eleven cases were conducted for NOD/SCID mice and nude mice modelling. The patient-derived lung cancer xenografts have been established successfully, and the tumor could be passed to new nude mice, including No 2 model (adenocasinoma, No. 3 model (small cell lung cancer, and No. 5 model (squamous cell cancer. High homogeneity was found between xenograft tumors and human lung cancer in histopathology, immunohistochemical phenotype, and EGFR, K-ras mutation status . The S-phase fraction of xenograft cell cycle was prolonged, which indicated that the xenografts remains highly proliferated. Conclusion The xenotransplantation models established for patient-derived lung cancer in immune deficient mice. The success rate is 27%. This model system displayed the biological characteristics of human lung cancer, suggesting that it may provide a stable, reliable, and useful animal model in human

  5. Coffee inhibits nuclear factor-kappa B in prostate cancer cells and xenografts. (United States)

    Kolberg, Marit; Pedersen, Sigrid; Mitake, Maiko; Holm, Kristine Lillebø; Bøhn, Siv Kjølsrud; Blomhoff, Heidi Kiil; Carlsen, Harald; Blomhoff, Rune; Paur, Ingvild


    Chronic inflammation contributes to prostate cancer and the transcription factor Nuclear Factor-kappa B (NF-κB) is constitutively active in most such cancers. We examine the effects of coffee on NF-κB and on the regulation of selected genes in human-derived prostate cancer cells (PC3) and in PC3 xenografts in athymic nude mice. PC3 cells stably transduced with an NF-κB-luciferase reporter were used both in vitro and for xenografts. NF-κB activity was measured by reporter assays, DNA binding and in vivo imaging. Gene expression was measured in PC3 cells, xenografts and tumor microenvironment by low-density arrays. Western blotting of activated caspases was used to quantify apoptosis. Coffee inhibited TNFα-induced NF-κB activity and DNA-binding in PC3 cells. Furthermore, coffee increased apoptosis and modulated expression of a number of inflammation- and cancer-related genes in TNFα-treated PC3 cells. In vivo imaging revealed a 31% lower NF-κB-luciferase activation in the xenografts of the mice receiving 5% coffee compared to control mice. Interestingly, we observed major changes in gene expression in the PC3 cells in xenografts as compared to PC3 cells in vitro. In PC3 xenografts, genes related to inflammation, apoptosis and cytoprotection were down-regulated in mice receiving coffee, and coffee also affected the gene expression in the xenograft microenvironment. Our data demonstrate that coffee inhibits NF-κB activity in PC3 cells in vitro and in xenografts. Furthermore, coffee modulates transcription of genes related to prostate cancer and inflammation. Our results are the first to suggest mechanistic links between coffee consumption and prostate cancer in an experimental mouse model.

  6. Patient-derived xenografts recapitulate molecular features of human uveal melanomas. (United States)

    Laurent, Cécile; Gentien, David; Piperno-Neumann, Sophie; Némati, Fariba; Nicolas, André; Tesson, Bruno; Desjardins, Laurence; Mariani, Pascale; Rapinat, Audrey; Sastre-Garau, Xavier; Couturier, Jérôme; Hupé, Philippe; de Koning, Leanne; Dubois, Thierry; Roman-Roman, Sergio; Stern, Marc-Henri; Barillot, Emmanuel; Harbour, J William; Saule, Simon; Decaudin, Didier


    We have previously developed a new method for the development and maintenance of uveal melanoma (UM) xenografts in immunodeficient mice. Here, we compare the genetic profiles of the primary tumors to their corresponding xenografts that have been passaged over time. The study included sixteen primary UMs and corresponding xenografts at very early (P1), early (P4), and late (P9) in vivo passages. The tumors were analyzed for mutation status of GNAQ, GNA11, GNAS, GNA15, BAP1, and BRAF, chromosomal copy number alterations using Affymetrix GeneChip(®) Genome-Wide Human SNP6.0 arrays, gene expression profiles using GeneChip(®) Human Exon 1.0 ST arrays, BAP1 mRNA and protein expression, and MAPK pathway status using Reverse Phase Protein Arrays (RPPA). The UM xenografts accurately recapitulated the genetic features of primary human UMs and they exhibited genetic stability over the course of their in vivo maintenance. Our technique for establishing and maintaining primary UMs as xenograft tumors in immunodeficient mice exhibit a high degree of genetic conservation between the primary tumors and the xenograft tumors over multiple passages in vivo. These models therefore constitute valuable preclinical tool for drug screening in UM.

  7. Xenograft survival in two species combinations using total-lymphoid irradiation and cyclosporine

    Energy Technology Data Exchange (ETDEWEB)

    Knechtle, S.J.; Halperin, E.C.; Bollinger, R.R.


    Total lymphoid irradiation (TLI) has profound immunosuppressive actions and has been applied successfully to allotransplantation but not xenotransplantation. Cyclosporine (CsA) has not generally permitted successful xenotransplantation of organs but has not been used in combination with TLI. TLI and CsA were given alone and in combination to rats that were recipients of hamster or rabbit cardiac xenografts. Combined TLI and CsA prolonged survival of hamster-to-rat cardiac xenografts from three days in untreated controls to greater than 100 days in most recipients. TLI alone significantly prolonged rabbit to rat xenograft survival with doubling of survival time. However, combined treatment did not significantly prolong rabbit-to-rat cardiac xenograft survival compared with TLI alone. The hamster and rat are phylogenetically closely related. Transplants from hamsters to rat are concordant xenografts since the time course of unmodified rejection is similar to first-set rejection of allografts. Although the rabbit-to-rat transplant is also between concordant species (average survival of untreated controls: 3.2 days) the rabbit and rat are more distantly related. These results suggest that TLI is an effective immunosuppressant when applied to cardiac xenotransplants in these animal models; that the choice of species critically affects xenograft survival when TLI and/or CsA are used for immunosuppression; and that the closely related species combination tested has markedly prolonged (greater than 100 days) survival using combined TLI and CsA.

  8. Stroma and extracellular matrix proteins in canine tumours



    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 myofibroblasts, and ECM changes were investigated. We found that the myofibroblast is the most common stromal cell in canine GIT epithelial tumours and most likely originated from pre-existing fibroblast...

  9. Sexual dimorphism in canine shape among extant great apes. (United States)

    Kelley, J


    There have been numerous attempts to sex fossil specimens using the canine dentition. Whether focused on canine size or canine shape, most of these efforts share two deficiencies: lack of quantification of male-female differences in the adopted criteria and a failure to adequately explore among extant species the discriminatory power of these criteria. Here, canine shape indices relating to relative canine height, upper canine root/crown proportionality, and relative length of the lower canine mesial ridge were calculated for males and females of all species and subspecies of extant great apes and two species of gibbons. The accuracy of these indices for identifying the sex of the extant ape specimens was investigated through discriminant analysis and the use of bivariate plots of the two upper and two lower canine indices. The indices were found to be highly accurate in identifying the sex of great ape individuals, not only in single-species and subspecies samples but in mixed-species samples as well; assignment error rates were mostly between 0 and 4%. Accuracy was lowest in Pan (error rates as high as 15%) and highest in Pongo (one error). In most cases, error rates were lower in the upper canines. The effectiveness of these shape indices for sexing might be related to the degree of absolute canine size dimorphism; the indices did not effectively segregate males and females among minimally canine-dimorphic gibbons. The mixed-species results reveal that same-sex index values are remarkably concordant across great ape species, as are the patterns of spatial segregation of males and females in the bivariate plots. Results suggest that, while the indices can be used with some confidence to sex individual fossil specimens, their greatest utility will be for identifying the sex of groups of canines united by size and morphology.

  10. 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;


    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...

  11. Developmental processes and canine dimorphism in primate evolution. (United States)

    Schwartz, Gary T; Miller, Ellen R; Gunnell, Gregg F


    Understanding the evolutionary history of canine sexual dimorphism is important for interpreting the developmental biology, socioecology and phylogenetic position of primates. All current evidence for extant primates indicates that canine dimorphism is achieved through bimaturism rather than via differences in rates of crown formation time. Using incremental growth lines, we charted the ontogeny of canine formation within species of Eocene Cantius, the earliest known canine-dimorphic primate, to test whether canine dimorphism via bimaturism was developmentally canalized early in primate evolution. Our results show that canine dimorphism in Cantius is achieved primarily through different rates of crown formation in males and females, not bimaturism. This is the first demonstration of rate differences resulting in canine dimorphism in any primate and therefore suggests that canine dimorphism is not developmentally homologous across Primates. The most likely interpretation is that canine dimorphism has been selected for at least twice during the course of primate evolution. The power of this approach is its ability to identify underlying developmental processes behind patterns of morphological similarity, even in long-extinct primate species.

  12. 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)


    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.

  13. Coryneform bacteria associated with canine otitis externa

    DEFF Research Database (Denmark)

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


    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...

  14. Breed predisposition to canine gastric carcinoma

    DEFF Research Database (Denmark)

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


    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...

  15. Impacted canines: Etiology, diagnosis, and orthodontic management

    Directory of Open Access Journals (Sweden)

    Ranjit Manne


    Full Text Available Impaction of maxillary and mandibular canines is a frequently encountered clinical problem, the treatment of which usually requires an interdisciplinary approach. Surgical exposure of the impacted tooth and the complex orthodontic mechanisms that are applied to align the tooth into the arch may lead to varying amounts of damage to the supporting structures of the tooth, not to mention the long treatment duration and the financial burden to the patient. Hence, it seems worthwhile to focus on the means of early diagnosis and interception of this clinical situation. In the present article, an overview of the incidence and sequelae, as well as the surgical, periodontal, and orthodontic considerations in the management of impacted canines is presented.

  16. Canine autoimmune hemolytic anemia: management challenges

    Directory of Open Access Journals (Sweden)

    Swann JW


    Full Text Available James W Swann,1 Barbara J Skelly2 1Queen Mother Hospital for Animals, The Royal Veterinary College, Hatfield, Hertfordshire, 2Department of Veterinary Medicine, University of Cambridge, Cambridge, UK Abstract: Immune-mediated hemolytic anemia is one of the most common manifestations of canine immune-mediated disease, yet treatment regimens remain nonstandardized and, in some cases, controversial. The main reason for this, as for most diseases in veterinary medicine, is the lack of large-scale placebo-controlled trials so that the efficacy of one treatment over another can be established. Most of the evidence used for treatment comes from retrospective studies and from personal preference and experience, and because of this, treatment regimens tend to vary among institutions and individual clinicians. Management of immune-mediated hemolytic anemia includes immunosuppression, thromboprophylaxis, and supportive care measures to help prevent and treat concurrent conditions. Keywords: IMHA, canine immune-mediated disease, management regimens

  17. The treatment of canine demodecosis with amitraz. (United States)

    Davis, D A


    The treatment of a series of 27 clinical cases of canine demodecosis is reported. Three of 4 applications of a wash containing 0,025% amitraz, together with antimicrobial and antipruritic therapy where necessary, were sufficient to effect clinical cure in 25 out of 26 cases mildly to severely affected. In one case, very severely affected, 9 weekly applications, together with antimicrobial and antipruritic therapy, effected clinical and parasitological cure.

  18. Treatment of canine scabies with milbemycin oxime. (United States)

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


    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.

  19. Increasing Incidence of Canine Leptospirosis in Switzerland

    Directory of Open Access Journals (Sweden)

    Andrea Major


    Full Text Available A marked increase in canine leptospirosis was observed in Switzerland over 10 years with a peak incidence of 28.1 diagnosed cases/100,000 dogs/year in the most affected canton. With 95% affected dogs living at altitudes <800 m, the disease presented a seasonal pattern associated with temperature (r2 0.73 and rainfall (r2 0.39, >90% cases being diagnosed between May and October. The increasing yearly incidence however was only weakly correlated with climatic data including number of summer (r2 0.25 or rainy days (r2 0.38. Serovars Australis and Bratislava showed the highest seropositivity rates with 70.5% and 69.1%, respectively. Main clinical manifestations included renal (99.6%, pulmonary (76.7%, hepatic (26.0%, and hemorrhagic syndromes (18.2%, leading to a high mortality rate (43.3%. Similar to the human disease, liver involvement had the strongest association with negative outcome (OR 16.3. Based on these data, canine leptospirosis presents similar features and severity as the human infection for which it therefore can be considered a model. Its re-emergence in a temperate country with very high incidence rates in canines should thus be viewed as a warning and emphasize the need for increased awareness in other species.

  20. Microbial profile of canine persistent wound infections

    Directory of Open Access Journals (Sweden)

    A. Padhy


    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.

  1. Coryneform bacteria associated with canine otitis externa. (United States)

    Aalbæk, Bent; Bemis, David A; Schjærff, Mette; Kania, Stephen A; Frank, Linda A; Guardabassi, Luca


    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 bacteria, mainly Staphylococcus pseudintermedius alone (n=5) or in combination with Malassezia pachydermatis (n=5). Some coryneform isolates displayed resistance to fusidic acid or enrofloxacin, two antimicrobial agents commonly used for the treatment of otitis externa in dogs. The frequency of isolation of coryneform bacteria was 16% among 55 cases of canine otitis externa examined at the Danish hospital during 2007. In contrast, detectable levels of coryneform bacteria were not demonstrated in samples from the acustic meatus of 35 dogs with apparently healthy ears, attending the hospital during the same year. On basis of the current knowledge, these coryneform bacteria should be regarded as potential secondary pathogens able to proliferate in the environment of an inflamed ear canal.

  2. Systematic analysis of a xenograft mice model for KSHV+ primary effusion lymphoma (PEL.

    Directory of Open Access Journals (Sweden)

    Lu Dai

    Full Text Available Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL, which arises preferentially in the setting of infection with human immunodeficiency virus (HIV. Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+ PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated in vivo exhibit unique biology, differing from one another or from their parental cell lines propagated through in vitro culture. Therefore, we used a KSHV(+ PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells in vivo display unique features to those passed in vitro, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.

  3. Anthocyanin Induces Apoptosis of DU-145 Cells In Vitro and Inhibits Xenograft Growth of Prostate Cancer (United States)

    Ha, U-Syn; Bae, Woong Jin; Kim, Su Jin; Yoon, Byung Il; Hong, Sung Hoo; Lee, Ji Youl; Hwang, Tae-Kon; Hwang, Sung Yeoun; Wang, Zhiping


    Purpose To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model). Materials and Methods The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2×106) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated. Results Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth. Conclusion This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model. PMID:25510742

  4. 9 CFR 113.317 - Parvovirus Vaccine (Canine). (United States)


    ... 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...

  5. Global epidemiology of canine rabies: past, present, and future prospects

    Directory of Open Access Journals (Sweden)

    Taylor LH


    Full Text Available Louise H Taylor,1 Louis H Nel1,21Global Alliance for Rabies Control, Manhattan, KS, USA; 2Department of Microbiology and Plant Pathology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa Abstract: The rabies virus, a public health scourge from ancient times, is currently responsible for an estimated 59,000 human deaths a year, almost all transmitted via dog bites. It causes considerable economic impacts on developing countries, primarily in Africa and Asia, which can least afford these losses. However, despite its almost 100% case fatality rate, canine rabies is a completely preventable disease, and historic examples of canine rabies elimination in the developed world attest to this. Over the last decade, programs based on eliminating the source of the disease from dogs have shown success in reducing the public health burden of canine rabies in developing countries, notably across Latin America, and this has contributed to the growing evidence base necessary to change attitudes toward the feasibility of global canine rabies elimination. More recently, assessments of the current economic burden of canine rabies and the potential cost savings achievable through mass dog vaccinations have been added to this evidence base. Tools and support are available from the international community to help countries move progressively toward canine rabies elimination, and there is optimism that global freedom from canine rabies can be achieved within the next few decades. Keywords: canine rabies, epidemiology, elimination, zoonosis, rabies virus

  6. Canine tooth size and fitness in male mandrills (Mandrillus sphinx). (United States)

    Leigh, Steven R; Setchell, Joanna M; Charpentier, Marie; Knapp, Leslie A; Wickings, E Jean


    Sexual selection theory explains the evolution of exaggerated male morphologies and weaponry, but the fitness consequences of developmental and age-related changes in these features remain poorly understood. This long-term study of mandrill monkeys (Mandrillus sphinx) demonstrates how age-related changes in canine tooth weaponry and adult canine size correlate closely with male lifetime reproductive success. Combining long-term demographic and morphometric data reveals that male fitness covaries simply and directly with canine ontogeny, adult maximum size, and wear. However, fitness is largely independent of other somatometrics. Male mandrills sire offspring almost exclusively when their canines exceed approximately 30 mm, or two-thirds of average adult value (45 mm). Moreover, sires have larger canines than nonsires. The tooth diminishes through wear as animals age, corresponding with, and perhaps influencing, reproductive senescence. These factors combine to constrain male reproductive opportunities to a brief timespan, defined by the period of maximum canine length. Sexually-selected weaponry, especially when it is nonrenewable like the primate canine tooth, is intimately tied to the male life course. Our analyses of this extremely dimorphic species indicate that sexual selection is closely intertwined with growth, development, and aging, pointing to new directions for sexual selection theory. Moreover, the primate canine tooth has potential as a simple mammalian system for testing genetically-based models of aging. Finally, the tooth may record details of life histories in fossil primates, especially when sexual selection has played a role in the evolution of dimorphism.

  7. Steady progression of osteoarthritic features in the canine groove model

    NARCIS (Netherlands)

    Marijnissen, A.C.A.; Roermund, P.M. van; Verzijl, N.; Tekoppele, J.M.; Bijlsma, J.W.J.; Lafeber, F.P.J.G.


    Objective: Recently we described a canine model of osteoarthritis (OA), the groove model with features of OA at 10 weeks after induction, identical to those seen in the canine anterior cruciate ligament transection (ACLT) model. This new model depends on cartilage damage accompanied by transient int

  8. Morphology and immunoreactivity of canine and feline extramedullary plasmacytomas. (United States)

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


    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.

  9. Recombinant canine distemper virus serves as bivalent live vaccine against rabies and canine distemper. (United States)

    Wang, Xijun; Feng, Na; Ge, Jinying; Shuai, Lei; Peng, Liyan; Gao, Yuwei; Yang, Songtao; Xia, Xianzhu; Bu, Zhigao


    Effective, safe, and affordable rabies vaccines are still being sought. Attenuated live vaccine has been widely used to protect carnivores from canine distemper. In this study, we generated a recombinant canine distemper virus (CDV) vaccine strain, rCDV-RVG, expressing the rabies virus glycoprotein (RVG) by using reverse genetics. The recombinant virus rCDV-RVG retained growth properties similar to those of vector CDV in Vero cell culture. Animal studies demonstrated that rCDV-RVG was safe in mice and dogs. Mice inoculated intracerebrally or intramuscularly with rCDV-RVG showed no apparent signs of disease and developed a strong rabies virus (RABV) neutralizing antibody response, which completely protected mice from challenge with a lethal dose of street virus. Canine studies showed that vaccination with rCDV-RVG induced strong and long-lasting virus neutralizing antibody responses to RABV and CDV. This is the first study demonstrating that recombinant CDV has the potential to serve as bivalent live vaccine against rabies and canine distemper in animals.

  10. Genome remodelling in a basal-like breast cancer metastasis and xenograft. (United States)

    Ding, Li; Ellis, Matthew J; Li, Shunqiang; Larson, David E; Chen, Ken; Wallis, John W; Harris, Christopher C; McLellan, Michael D; Fulton, Robert S; Fulton, Lucinda L; Abbott, Rachel M; Hoog, Jeremy; Dooling, David J; Koboldt, Daniel C; Schmidt, Heather; Kalicki, Joelle; Zhang, Qunyuan; Chen, Lei; Lin, Ling; Wendl, Michael C; McMichael, Joshua F; Magrini, Vincent J; Cook, Lisa; McGrath, Sean D; Vickery, Tammi L; Appelbaum, Elizabeth; Deschryver, Katherine; Davies, Sherri; Guintoli, Therese; Lin, Li; Crowder, Robert; Tao, Yu; Snider, Jacqueline E; Smith, Scott M; Dukes, Adam F; Sanderson, Gabriel E; Pohl, Craig S; Delehaunty, Kim D; Fronick, Catrina C; Pape, Kimberley A; Reed, Jerry S; Robinson, Jody S; Hodges, Jennifer S; Schierding, William; Dees, Nathan D; Shen, Dong; Locke, Devin P; Wiechert, Madeline E; Eldred, James M; Peck, Josh B; Oberkfell, Benjamin J; Lolofie, Justin T; Du, Feiyu; Hawkins, Amy E; O'Laughlin, Michelle D; Bernard, Kelly E; Cunningham, Mark; Elliott, Glendoria; Mason, Mark D; Thompson, Dominic M; Ivanovich, Jennifer L; Goodfellow, Paul J; Perou, Charles M; Weinstock, George M; Aft, Rebecca; Watson, Mark; Ley, Timothy J; Wilson, Richard K; Mardis, Elaine R


    Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo mutations and a large deletion not present in the primary tumour, and was significantly enriched for 20 shared mutations. The xenograft retained all primary tumour mutations and displayed a mutation enrichment pattern that resembled the metastasis. Two overlapping large deletions, encompassing CTNNA1, were present in all three tumour samples. The differential mutation frequencies and structural variation patterns in metastasis and xenograft compared with the primary tumour indicate that secondary tumours may arise from a minority of cells within the primary tumour.

  11. Simultaneous canine distemper encephalitis and canine parvovirus infection with distemper-associated cardiac necrosis in a pup


    HEADLEY, Selwyn Arlington; Saito,Taís Berelli


    Simultaneous infection of canine distemper virus and canine parvovirus associated with distemper myocardial degeneration and necrosis is described in a pup. The dog demonstrated myoclonus, nystagmus, enamel hypoplasia, abdominal pustules, and bilateral corneal ulceration clinically. Demyelinating encephalitis, myocardial degeneration and necrosis with mineralization, and necrosis, hemorrhage and fusion of intestinal villi were observed. The lesions observed in this dog are characteristic of a...

  12. Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts

    DEFF Research Database (Denmark)

    Rygaard, K; Møller, C; Bock, E


    characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were...... embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression....

  13. Patient-derived xenografts: A platform for accelerating translational research in prostate cancer. (United States)

    Davies, Alastair H; Wang, Yuzhuo; Zoubeidi, Amina


    Recently, there has been renewed interest in the development and characterization of patient-derived tumour xenograft (PDX) models. Numerous PDX models have been established for prostate cancer and, importantly, retain the principal molecular, genetic, and histological characteristics of the donor tumour. As such, these models provide significant improvements over standard cell line xenograft models for biological studies, preclinical drug development, and personalized medicine strategies. This review summarizes the current state of the art in this field, illustrating the opportunities and limitations of PDX models in translational prostate cancer research.

  14. [Effects of baicalin on HL-60 cell xenografts in nude mice and its mechanism]. (United States)

    Zheng, Jing; Hu, Jian-Da; Huang, Yi; Chen, Ying-Yu; Li, Jing; Chen, Bu-Yuan


    This study was aimed to investigate the effects of baicalin on HL-60 cell xenografts in nude mice in vivo and explore its mechanism. Xenograft tumor model of HL-60 cells in nude mice was established, which was divided randomly into 6 groups: negative control group (injection of 5% NaHCO(3)), 25, 50 and 100 mg/kg baicalin groups, combination group (50 mg/kg baicalin + 2 mg/kg VP16) and positive control group (VP16 4 mg/kg). The nude mice with HL-60 cell xenografts were treated with drugs via intraperitoneal injection daily. After treatment for 14 days average weigh and inhibitory rate of transplanted tumor stripped from 5 nude mice in each group were calculated, and the ultrastructure change of xenografts cells were tested by transmission electron microscopy. Histopathologic examination was used to observed the change of main organs in nude mice. The expression of signaling molecular PI3K/Akt proteins extracted from xenografts was detected by Western blot. The effects of baicalin on overall survival time in nude mice with HL-60 cell xenografts were evaluated. The results showed that baicalin could inhibit the growth of transplanted tumors in dose-dependent manner. There were more necrotic and apoptotic cells in mice of baicalin-treated groups and combination group than that in mice of negative control group. Baicalin could inhibit the proliferation of HL-60 cells in vivo by down-regulating the PI3K/Akt/mTOR signal pathway, where the expressions of p-Akt, mTOR and p-mTOR proteins decreased compared with negative control group, and no significant difference of Akt expression was found between different groups. Compared with negative control group, the median survival time of mice in combination group was more prolongated (P HL-60 cell xenografts in nude mice, and prolong median survival time of nude mice. The possible mechanisms may be related to inhibition of Akt activity and down-regulation of the PI3K/Akt/mTOR signal pathway. The combination of baicalin and VP16

  15. Extraglandular and intraglandular vascularization of canine prostate. (United States)

    Stefanov, Miroslav


    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.

  16. Canine parvovirus in asymptomatic feline carriers. (United States)

    Clegg, S R; Coyne, K P; Dawson, S; Spibey, N; Gaskell, R M; Radford, A D


    Canine parvovirus (CPV) and feline panleukopaenia virus (FPLV) are two closely related viruses, which are known to cause severe disease in younger unvaccinated animals. As well as causing disease in their respective hosts, CPV has recently acquired the feline host range, allowing it to infect both cats and dogs. As well as causing disease in dogs, there is evidence that under some circumstances CPV may also cause disease in cats. This study has investigated the prevalence of parvoviruses in the faeces of clinically healthy cats and dogs in two rescue shelters. Canine parvovirus was demonstrated in 32.5% (13/50) of faecal samples in a cross sectional study of 50 cats from a feline only shelter, and 33.9% (61/180) of faecal samples in a longitudinal study of 74 cats at a mixed canine and feline shelter. Virus was isolated in cell cultures of both canine and feline origin from all PCR-positive samples suggesting they contained viable, infectious virus. In contrast to the high CPV prevalence in cats, no FPLV was found, and none of 122 faecal samples from dogs, or 160 samples collected from the kennel environment, tested positive for parvovirus by PCR. Sequence analysis of major capsid VP2 gene from all positive samples, as well as the non-structural gene from 18 randomly selected positive samples, showed that all positive cats were shedding CPV2a or 2b, rather than FPLV. Longitudinally sampling in one shelter showed that all cats appeared to shed the same virus sequence type at each date they were positive (up to six weeks), despite a lack of clinical signs. Fifty percent of the sequences obtained here were shown to be similar to those recently obtained in a study of sick dogs in the UK (Clegg et al., 2011). These results suggest that in some circumstances, clinically normal cats may be able to shed CPV for prolonged periods of time, and raises the possibility that such cats may be important reservoirs for the maintenance of infection in both the cat and the dog

  17. 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)


    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.

  18. 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


    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.

  19. Intracellular route of canine parvovirus entry. (United States)

    Vihinen-Ranta, M; Kalela, A; Mäkinen, P; Kakkola, L; Marjomäki, V; Vuento, M


    The present study was designed to investigate the endocytic pathway involved in canine parvovirus (CPV) infection. Reduced temperature (18 degrees C) or the microtubule-depolymerizing drug nocodazole was found to inhibit productive infection of canine A72 cells by CPV and caused CPV to be retained in cytoplasmic vesicles as indicated by immunofluorescence microscopy. Consistent with previously published results, these data indicate that CPV enters a host cell via an endocytic route and further suggest that microtubule-dependent delivery of CPV to late endosomes is required for productive infection. Cytoplasmic microinjection of CPV particles was used to circumvent the endocytosis and membrane fusion steps in the entry process. Microinjection experiments showed that CPV particles which were injected directly into the cytoplasm, thus avoiding the endocytic pathway, were unable to initiate progeny virus production. CPV treated at pH 5.0 prior to microinjection was unable to initiate virus production, showing that factors of the endocytic route other than low pH are necessary for the initiation of infection by CPV.

  20. Expression of Bcl-2 in canine osteosarcoma

    Directory of Open Access Journals (Sweden)

    F. Piro


    Full Text Available Osteosarcoma (OS is the most common primary malignancy of bone. It is responsible for 80-85% of the primary bone tumors affecting dogs and it is characterized by aggressive and invasive behavior, with a high metastatic potential. Several studies on cancer and related tumorigenesis, show an involvement of the mechanisms of programmed cell death and cell survival. Many signals seem to be involved in the related mechanism of autophagy and in particular, our interest is focused on the expression of a family of Bcl-2 that seems to be involved either in the control of biomolecular mechanisms like autophagy and apoptosis. In this study we investigated the expression of Bcl-2 in different cases of spontaneous canine osteosarcoma and the related preliminary results are described. We found Bcl-2 activity was increased in OS tissue compared to normal bone tissue. These results suggested that Bcl-2 activity may play an important role in the formation of OS and as a diagnostic for neoplastic activity. However, further research is needed to confirm the role of Bcl-2 activity in OS in canines.

  1. 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


    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.

  2. Canine Models for Copper Homeostasis Disorders

    Directory of Open Access Journals (Sweden)

    Xiaoyan Wu


    Full Text Available Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted.

  3. Seroepidemiology of Canine parvovirus infection in dogs

    Directory of Open Access Journals (Sweden)

    Indrawati Sendow


    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.

  4. Mechanism of Growth Inhibition of Prostate Cancer Xenografts by Valproic Acid

    Directory of Open Access Journals (Sweden)

    Abhinav Sidana


    Full Text Available Valproic Acid (VPA, a histone deacetylase inhibitor, has been demonstrated to cause a marked decrease in proliferation of prostate cancer (PCa cells in vitro and a significant reduction in tumor volume in vivo. The goal of this study is to better understand the VPA-induced growth inhibition in vivo, by studying expression of various markers in PCa xenografts. Methods. For in vitro experiments, PCa cells were treated with 0, 0.6, and 1.2 mM VPA for 14 days. For in vivo models, experimental animals received 0.4% VPA in drinking water for 35 days. Tissue microarray was generated using cell pellets and excised xenografts. Results. VPA treatment causes cell cycle arrest in PCa cells in vivo, as determined by increase in p21 and p27 and decrease in cyclin D1 expression. Increased expression of cytokeratin18 was also seen in xenografts. LNCaP xenografts in treated animals had reduced androgen receptor (AR expression. While decreased proliferation was found in vitro, increase in apoptosis was found to be the reason for decreased tumor growth in vivo. Also, an anti-angiogenic effect was observed after VPA treatment. Conclusion. VPA inhibits tumor growth by multiple mechanisms including cell cycle arrest, induction of differentiation, and inhibition of growth of tumor vasculature.

  5. A membrane cofactor protein transgenic mouse model for the study of discordant xenograft rejection.

    NARCIS (Netherlands)

    N. Yannoutsos (Nikos); J.N.M. IJzermans (Jan); C. Harkes; F. Bonthuis (Fred); C-Y. Zhou; D. White; R.L.M. Marquet; F.G. Grosveld (Frank)


    textabstractBACKGROUND: In recent years, interest has been revived in the possibility of transplanting organs into humans from a phylogenetically disparate species such as the pig (xenotransplantation). Such discordant xenografts, however, are subject to hyperacute rejection (HAR) and activation of

  6. Patient-Derived Xenograft Models : An Emerging Platform for Translational Cancer Research

    NARCIS (Netherlands)

    Hidalgo, Manuel; Amant, Frederic; Biankin, Andrew V.; Budinska, Eva; Byrne, Annette T.; Caldas, Carlos; Clarke, Robert B.; de Jong, Steven; Jonkers, Jos; Maelandsmo, Gunhild Mari; Roman-Roman, Sergio; Seoane, Joan; Trusolino, Livio; Villanueva, Alberto


    Recently, there has been an increasing interest in the development and characterization of patient-derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor and remain stable across passages. These mod

  7. Establishment and characterization of human uveal malignant melanoma xenografts in nude mice

    DEFF Research Database (Denmark)

    Heegaard, S; Spang-Thomsen, M; Prause, J U


    and electron microscopy. Only one of the eight transplanted primary tumours (13%) was established as a xenograft in nude mice. Furthermore, the take rate of the transplantable tumour was low (13%). The growth of the tumour fitted a Gompertz function, and the calculated tumour volume doubling time was 54 days...

  8. The T61 human breast cancer xenograft: an experimental model of estrogen therapy of breast cancer

    DEFF Research Database (Denmark)

    Brunner, N; Spang-Thomsen, M; Cullen, K


    Endocrine therapy is one of the principal treatment modalities of breast cancer, both in an adjuvant setting and in advanced disease. The T61 breast cancer xenograft described here provides an experimental model of the effects of estrogen treatment at a molecular level. T61 is an estrogen recepto...

  9. Canine leishmaniasis: epidemiological risk and the experimental model. (United States)

    Moreno, Javier; Alvar, Jorge


    Increasing risk factors are making zoonotic visceral leishmaniasis a growing public health concern in many countries. Domestic dogs constitute the main reservoir of Leishmania infantum and Leishmania chagasi, and play a key role in the transmission to humans. New reagents and tools allow the detailed investigation of canine leishmaniasis, permitting the monitoring of the immunological status of dogs in both natural and experimental infections. Such studies are essential to determine the basis of the canine protective immune response and to establish a laboratory model, a significant aspect for the development of vaccines against canine leishmaniasis.

  10. Unilateral Maxillary Canine Agenesis: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Nagihan Koç


    Full Text Available Congenital absence of maxillary permanent canines is an extremely rare condition, which may appear as part of a syndrome or as a nonsyndromic form. Nonsyndromic canine agenesis combined with other types of tooth agenesis has occasionally been described in the literature but isolated cases are rarely observed. This report presents an isolated case of maxillary permanent canine agenesis in a healthy 18-year-old female patient and a literature review on the prevalence, etiology, and differential diagnosis of the condition.

  11. A custom made jig for individual canine retraction

    Directory of Open Access Journals (Sweden)

    Vipul Kumar Sharma


    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.

  12. Kinetics of canine dental calculus crystallization: an in vitro study on the influence of inorganic components of canine saliva. (United States)

    Borah, Ballav M; Halter, Timothy J; Xie, Baoquan; Henneman, Zachary J; Siudzinski, Thomas R; Harris, Stephen; Elliott, Matthew; Nancollas, George H


    This work identifies carbonated hydroxyapatite (CAP) as the primary component of canine dental calculus, and corrects the long held belief that canine dental calculus is primarily CaCO3 (calcite). CAP is known to be the principal crystalline component of human dental calculus, suggesting that there are previously unknown similarities in the calcification that occurs in these two unique oral environments. In vitro kinetic experiments mimicking the inorganic components of canine saliva have examined the mechanisms of dental calculus formation. The solutions were prepared so as to mimic the inorganic components of canine saliva; phosphate, carbonate, and magnesium ion concentrations were varied individually to investigate the roll of these ions in controlling the nature of the phases that is nucleated. To date, the inorganic components of the canine oral systems have not been investigated at concentrations that mimic those in vivo. The mineral composition of the synthetic calculi grown under these conditions closely resembled samples excised from canines. This finding adds new information about calculus formation in humans and canines, and their sensitivity to chemicals used to treat these conditions.

  13. Canine Visceral Leishmaniasis in Wild Canines (Fox, Jackal, and Wolf in Northeastern Iran Using Parasitological, Serological, and Molecular Methods

    Directory of Open Access Journals (Sweden)

    Mehdi Mohebali


    Full Text Available Background: Although many studies had been conducted on various aspects of canine visceral leishmaniasis (CVL in domestic dogs in the endemic areas of Iran, investigations on CVL in wild canines are rare.Methods: This is a cross-sectional study was conducted from December 2012 to 2013 in northeast of Iran where human VL is endemic. Wild canines were trapped around the areas where human VL cases had been previously identified. Wild canines were collected and examined both clinically and serologically using direct agglutination test (DAT. Microscopically examinations were performed in all the seropositive wild canines for the presence of the amastigote form of Leishmania spp. Some Leishmania sp. which had been isolated from the spleens of wild canines, were examined analyzed by conventional PCR and sequencing techniques using α-tubulin and GAPDH genes.Results: Altogether, 84 wild canines including foxes (Vulpes vulpes, n=21, Jackals (Canis aureus, n=60 and wolves (Canis lupus, n=3 were collected. Four foxes and seven jackals showed anti-Leishmania infantum antibodies with titers of 1:320–1:20480 in DAT. Furthermore, one fox and one jackal were parasitologically (microscopy and culture positive and L. infantum was confirmed by sequence analysis.Conclusion: The present study showed that sylvatic cycle of L. infantum had been established in the studied endemic areas of VL in northeastern Iran.

  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


    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. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

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    Francis Richard W


    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  16. Xenograft assessment of predictive biomarkers for standard head and neck cancer therapies. (United States)

    Stein, Andrew P; Swick, Adam D; Smith, Molly A; Blitzer, Grace C; Yang, Robert Z; Saha, Sandeep; Harari, Paul M; Lambert, Paul F; Liu, Cheng Z; Kimple, Randall J


    Head and neck squamous cell carcinoma (HNSCC) remains a challenging cancer to treat with overall 5-year survival on the order of 50-60%. Therefore, predictive biomarkers for this disease would be valuable to provide more effective and individualized therapeutic approaches for these patients. While prognostic biomarkers such as p16 expression correlate with outcome; to date, no predictive biomarkers have been clinically validated for HNSCC. We generated xenografts in immunocompromised mice from six established HNSCC cell lines and evaluated response to cisplatin, cetuximab, and radiation. Tissue microarrays were constructed from pre- and posttreatment tumor samples derived from each xenograft experiment. Quantitative immunohistochemistry was performed using a semiautomated imaging and analysis platform to determine the relative expression of five potential predictive biomarkers: epidermal growth factor receptor (EGFR), phospho-EGFR, phospho-Akt, phospho-ERK, and excision repair cross-complementation group 1 (ERCC1). Biomarker levels were compared between xenografts that were sensitive versus resistant to a specific therapy utilizing a two-sample t-test with equal standard deviations. Indeed the xenografts displayed heterogeneous responses to each treatment, and we linked a number of baseline biomarker levels to response. This included low ERCC1 being associated with cisplatin sensitivity, low phospho-Akt correlated with cetuximab sensitivity, and high total EGFR was related to radiation resistance. Overall, we developed a systematic approach to identifying predictive biomarkers and demonstrated several connections between biomarker levels and treatment response. Despite these promising initial results, this work requires additional preclinical validation, likely involving the use of patient-derived xenografts, prior to moving into the clinical realm for confirmation among patients with HNSCC.

  17. Minute virus of canines (MVC, canine parvovirus type-1): pathogenicity for pups and seroprevalence estimate. (United States)

    Carmichael, L E; Schlafer, D H; Hashimoto, A


    Minute virus of canines (MVC, canine parvovirus type-1) caused inapparent to severe illness in neonatal specific-pathogen-free pups exposed by the oronasal route. The experimental disease was generally mild. Four of 21 infected pups had clinical signs of respiratory illness, but only 2 pups, not euthanized during the early postinoculation period, developed severe illness or died. Principal pathologic changes included bronchitis and interstitial pneumonia with various degrees of lymphadenitis. In contrast to the reported field cases, enteric signs were absent in the experimentally infected animals. Histopathologic changes in the small intestine were mild or absent. Bronchial, bronchiolar, and alveolar epithelial cells appeared to be the sites of initial and most extensive viral growth, reflecting the pattern of histopathologic changes. The disease caused by MVC was mild in comparison to that caused by canine parvovirus-type 2. MVC now appears to be established as a cause of illness in young pups and of transplacental infections with embryo resorption. The prevalence of MVC hemagglutination-inhibiting antibodies was high (approximately 50%) in adult dog sera from widely separated geographic areas of the United States.

  18. Emerging perspectives on hereditary glomerulopathies in canines

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    Littman MP


    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

  19. Removal of retained upper canine in the middle. Case report

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    Bienvenido Mesa Reinaldo


    Full Text Available The inclusion of upper canine is one of the most common retentions that occur in permanent teething, this event may be related to that, this is the last tooth to erupt in the lower, also is associated with involution of the jaws, because eruption path is long and complex, often facing unfavorable. A case of a female patient, aged 25, of rural origin, which does not suffer from any disease, which was seen because of discomfort in area 23, ie in the left upper permanent canine. It was noted in the oral examination persistent left superior temporal canine, 63, and periapical and panoramic X-rays showed the presence of 23 included in an intermediate position. It was decided to make a modification of surgical technique with a conservative view of the palatal cortical bone. Was performed successfully including resection of the canine.

  20. Periodontal ligament distraction: A simplified approach for rapid canine retraction

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    K C Prabhat


    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.

  1. Canine index – A tool for sex determination

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    Shankar M. Bakkannavar


    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. The Comparative Diagnostic Features of Canine and Human Lymphoma

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    Davis M. Seelig


    Full Text Available The non-Hodgkin lymphomas (NHLs are a heterogeneous family of lymphoid malignancies that are among the most common neoplasms of both dogs and humans. Owing to shared molecular, signaling, incidence, and pathologic features, there is a strong framework supporting the utilization of canine lymphoma as a comparative, large animal model of human NHL. In alignment with the biologic similarities, the current approach towards the diagnosis and classification of canine lymphoma is based upon the human World Health Organization guidelines. While this approach has contributed to an increasing appreciation of the potential biological scope of canine lymphoma, it has also become apparent that the most appropriate diagnostic philosophy must be multimodal, namely by requiring knowledge of microscopic, immunophenotypic, and clinical features before establishing a final disease diagnosis. This review seeks to illustrate the comparative similarities and differences in the diagnosis of canine lymphoma through the presentation of the microscopic and immunophenotypic features of its most common forms.

  3. Canine heartworm disease: a review and pilot study. (United States)

    Haddock, K C


    Canine heartworm disease is a mosquito vectored illness resulting from parasitization by the filariid worm Dirofilaria immitis. While presenting some danger to humans, the filariid has its greatest impact on the canine population. In recent years the disease has become established throughout much of the United States, perhaps as the result of diffusion from a suspected hearth in the southeastern coastal plain. While its distribution is known in general terms, much research remains to be done to assess the pattern of distribution as well as the impact of D. immitis on canine populations and their human owners for many locales. The present study provides a review of the literature on the parasite; on its distribution, particularly in the United States; and on the ecology of canine heartworm disease. A pilot study is presented which emphasizes the problems encountered in establishing a data base for observations on the disease at the local level.

  4. Severe canine distemper outbreak in unvaccinated dogs in Mozambique

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    Julieta Zacarias


    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

  5. Death of a wild wolf from canine parvovirus enteritis (United States)

    Mech, L.D.; Kurtz, H.J.; Goyal, S.


    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.

  6. Genomic instability and telomere fusion of canine osteosarcoma cells.

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    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.

  7. A Compendium of Canine Normal Tissue Gene Expression


    Joseph Briggs; Melissa Paoloni; Qing-Rong Chen; Xinyu Wen; Javed Khan; Chand Khanna


    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 platf...

  8. Establishment of a PCR analysis method for canine BRCA2

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    Yoshikawa Yasunaga


    Full Text Available Abstract Background Mammary tumors are the most common tumor type in both human and canine females. In women, carriers of mutations in BRCA2, a tumor suppressor gene product, have a higher risk of breast cancer. Canine BRCA2 has also been suggested to have a relationship with mammary tumors. However, clearly deleterious BRCA2 mutations have not been identified in any canine mammary tumors, as appropriate methods to detect mutations or a consensus BRCA2 sequence have not been reported. Findings For amplification and sequencing of BRCA2, we designed 14 and 20 PCR primer sets corresponding to the BRCA2 open reading frame (ORF and all 27 exons, respectively, including exon-intron boundaries of the canine BRCA2 regions, respectively. To define the consensus canine BRCA2 ORF sequence, we used established methods to sequence the full-length canine BRCA2 ORF sequence from two ovaries and a testis obtained from individual healthy mongrel dogs and partially sequence BRCA2 genomic sequences in 20-56 tumor-free dogs, each aged over 6 years. Subsequently, we compared these sequences and seven previously reported sequences, and defined the most common base sequences as the consensus canine BRCA2 ORF sequence. Moreover, we established a detection method for identifying splicing variants. Unexpectedly, we also identified novel splicing variants in normal testes during establishment of these methods. Conclusions The present analysis methods for determining the BRCA2 base sequence and for detecting BRCA2 splicing variants and the BRCA2 ORF consensus sequence are useful for better understanding the relationship between canine BRCA2 mutation status and cancer risk.

  9. Current practices and research updates on diabetes mellitus in canine


    Pankaj Kumar; Rashmi Rekha Kumari; Manish Kumar; Sanjiv Kumar; Asit Chakrabarti


    Diabetes has evidence in ancient literatures, though recently is being considered as one amongst the most emerging disease condition in both human and companion animals. Diabetes mellitus is one of the common endocrinopathy of dog characterized by hyperglycemia, glycosuria and weight loss. Reports suggests high fraction of canine population suffer with diabetes world over. Studies in different veterinary hospitals of United States suggest increase in cases of canine diabetes and decrease in c...

  10. Transmigration of Mandibular Canine: Report of Four Cases and Review of Literature

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    Gaurav Sharma


    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.

  11. Canine vector-borne diseases in Brazil

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    Dantas-Torres Filipe


    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.

  12. Canine renal failure syndrome in three dogs. (United States)

    Jeong, Won Il; Do, Sun Hee; Jeong, Da Hee; Chung, Jae Yong; Yang, Hai Jie; Yuan, Dong Wei; Hong, Il Hwa; Park, Jin Kyu; Goo, Moon Jung; Jeong, Kyu Shik


    Three dead dogs were brought to the College of Veterinary Medicine, Kyungpook National University for study. Clinically, all the dogs showed emaciation, anorexia, depression, hemorrhagic vomiting and diarrhea for 7-10 days before death. All the clinical signs were first noted for about one month after feeding the dogs with commercial diets. At necropsy, all 3 dogs had severe renal damage with the same green-yellowish colored nephroliths in the renal pelvis. They also showed systemic hemorrhage and calcification of several organs, which might have been induced by uremia. Microscopically, necrosis, calcification and calculi were detected in the renal tubules, and especially in the proximal convoluted tubules and collecting ducts of the kidney. These findings were supportive of a mycotoxic effect, and especially on their kidneys. However, the precise cause of the toxic effect in these cases of canine renal failure could not be determined.

  13. Ultrasonographic evaluation of canine supraspinatus calcifying tendinosis. (United States)

    Mistieri, Maria Ligia A; Wigger, Antje; Canola, Julio C; Filho, João G P; Kramer, Martin


    Supraspinatus calcifying tendinosis is an uncommon finding in dogs. Although its radiographic appearance has been described previously, radiographs alone do not provide detailed information about the tendon parenchyma. Tendon ultrasonography has been widely applied for the diagnosis of human tendinosis, but it remains underused in dogs. This article reviews the ultrasonographic technique and variable appearance of canine supraspinatus calcifying tendinosis observed in 33 tendons. The ultrasonographic findings are described. The most common ultrasonographic finding was a hyperechoic area accompanied by distal acoustic shadowing. No relationship with bicipital tenosynovitis was found. A color Doppler examination was possible in only five of the tendons, revealing no blood flow in those tendons. There was evidence that the presence of a hypoechoic area surrounding the calcification was related to clinical signs of pain, suggesting an active inflammatory process. Ultrasonography was an excellent technique to evaluate lesions of the supraspinatus tendon and it revealed details not apparent on radiographs.

  14. Calcareous degeneration of the canine cornea. (United States)

    Sansom, Jane; Blunden, Tony


    The purpose of this paper is to describe a specific presentation of canine corneal calcification. Fourteen cases are described. In seven cases the corneal lesions were bilaterally symmetrical. In five cases the corneal lesion was unilateral. Two dogs were uniocular, the contralateral eye had been enucleated between 1 and 3 months previously by the referring veterinary surgeon following corneal ulceration and perforation. Of a total of 21 eyes with corneal calcification, 16 eyes had associated ulceration. The ulceration presented as follows: two eyes had descemetocoeles, four eyes had corneal perforations, eight eyes had stromal ulceration, and two eyes had superficial punctate ulceration. The cause of the corneal mineralization remains undetermined but underlying systemic disease, particularly hyperadrenocorticism (Cushing's Syndrome), is suspected as a possible contributing factor in some of these cases. Histopathology was carried out on three cases following a keratectomy and placement of a conjunctival pedicle flap into the ulcerated lesion.

  15. Canine distemper in endangered Ethiopian wolves. (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


    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.

  16. Canine tooth dimorphism: An adjunct for establishing sex identity

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    Madhavi Yuwanati


    Full Text Available Background: Teeth are an excellent material for genetic, odontological and forensic investigations and research purpose. From all the teeth, the mandibular canines are found to exhibit sexual dimorphism. However, very few studies have been published on maxillary canine′s measurements. Aims: 1. To find out utility of maxillary and mandibular canine width as a tool for sex determination in Central Indian population. 2. To find out the average size of canines in males and females of Central Indian population. 3. To compare the findings with National and International studies Materials and Methods: The present study was conducted in 100 cases in the age group of 17-21 years. Mesiodistal width of right and left mandibular and maxillary canines were measured on the casts with digital calliper and subjected to statistical analysis. Statistical Analysis: Statistical analysis was done to assess sex difference using Students ′t′ test (paired. Results and Conclusions: It was seen that a definite statistically significant sexual dimorphism exists when mandibular and maxillary canine measurements were compared. Thus, it can be suggested that canine width measurements can be used as an adjunct for sex identification purpose in Central Indian Population.

  17. Chlamydia in canine or feline coronary arteriosclerotic lesions

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    Grabarevic Zeljko


    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.

  18. Consequences of crown shortening canine teeth in Greenland sled dogs

    DEFF Research Database (Denmark)

    Kortegaard, H E; Anthony Knudsen, T; Dahl, S


    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...

  19. Current practices and research updates on diabetes mellitus in canine

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    Pankaj Kumar


    Full Text Available Diabetes has evidence in ancient literatures, though recently is being considered as one amongst the most emerging disease condition in both human and companion animals. Diabetes mellitus is one of the common endocrinopathy of dog characterized by hyperglycemia, glycosuria and weight loss. Reports suggests high fraction of canine population suffer with diabetes world over. Studies in different veterinary hospitals of United States suggest increase in cases of canine diabetes and decrease in case fatality rate over time. Increase in cases of canine diabetes worldwide is attributed to awareness amongst pet owners, better veterinary health facilities, breed preferences by dog owners, increase dependence on commercial feeds, obesity, etc. Diabetes in most dogs is immune mediated and insulin dependent. Breed predisposition in canine is attributed to dog leukocyte antigen gene pool encoding form major histocompatibility complex-II molecules, however research is still underway. Diagnosis of diabetes still relies on blood sugar evaluation for screening of canine population, though many other diagnostic methods have shown promising benefits including measurement of fructosamine and glycated haemoglobin. Management of diabetes in dog is based on insulin therapy, diet modification and exercise. Use of oral anti-diabetics drugs in canine is limited though experimental studies have shown promising results. Alternative therapies have been explored, but only a few approaches have shown promise for clinical application.

  20. An integrated analysis of miRNA and gene copy numbers in xenografts of Ewing's sarcoma

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    Mosakhani Neda


    Full Text Available Abstract Background Xenografts have been shown to provide a suitable source of tumor tissue for molecular analysis in the absence of primary tumor material. We utilized ES xenograft series for integrated microarray analyses to identify novel biomarkers. Method Microarray technology (array comparative genomic hybridization (aCGH and micro RNA arrays was used to screen and identify copy number changes and differentially expressed miRNAs of 34 and 14 passages, respectively. Incubated cells used for xenografting (Passage 0 were considered to represent the primary tumor. Four important differentially expressed miRNAs (miR-31, miR-31*, miR-145, miR-106 were selected for further validation by real time polymerase chain reaction (RT-PCR. Integrated analysis of aCGH and miRNA data was performed on 14 xenograft passages by bioinformatic methods. Results The most frequent losses and gains of DNA copy number were detected at 9p21.3, 16q and at 8, 15, 17q21.32-qter, 1q21.1-qter, respectively. The presence of these alterations was consistent in all tumor passages. aCGH profiles of xenograft passages of each series resembled their corresponding primary tumors (passage 0. MiR-21, miR-31, miR-31*, miR-106b, miR-145, miR-150*, miR-371-5p, miR-557 and miR-598 showed recurrently altered expression. These miRNAS were predicted to regulate many ES-associated genes, such as genes of the IGF1 pathway, EWSR1, FLI1 and their fusion gene (EWS-FLI1. Twenty differentially expressed miRNAs were pinpointed in regions carrying altered copy numbers. Conclusion In the present study, ES xenografts were successfully applied for integrated microarray analyses. Our findings showed expression changes of miRNAs that were predicted to regulate many ES associated genes, such as IGF1 pathway genes, FLI1, EWSR1, and the EWS-FLI1 fusion genes.

  1. Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia

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    Berthou Christian


    Full Text Available Abstract Background We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL and leukemia B cell lines. Results Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively. The same treatment of mice which were not xenografted induced no mortality. Conclusion These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.

  2. Raman spectroscopy identifies radiation response in human non-small cell lung cancer xenografts (United States)

    Harder, Samantha J.; Isabelle, Martin; Devorkin, Lindsay; Smazynski, Julian; Beckham, Wayne; Brolo, Alexandre G.; Lum, Julian J.; Jirasek, Andrew


    External beam radiation therapy is a standard form of treatment for numerous cancers. Despite this, there are no approved methods to account for patient specific radiation sensitivity. In this report, Raman spectroscopy (RS) was used to identify radiation-induced biochemical changes in human non-small cell lung cancer xenografts. Chemometric analysis revealed unique radiation-related Raman signatures that were specific to nucleic acid, lipid, protein and carbohydrate spectral features. Among these changes was a dramatic shift in the accumulation of glycogen spectral bands for doses of 5 or 15 Gy when compared to unirradiated tumours. When spatial mapping was applied in this analysis there was considerable variability as we found substantial intra- and inter-tumour heterogeneity in the distribution of glycogen and other RS spectral features. Collectively, these data provide unique insight into the biochemical response of tumours, irradiated in vivo, and demonstrate the utility of RS for detecting distinct radiobiological responses in human tumour xenografts.

  3. Molecular characterization of EGFR and EGFRvIII signaling networks in human glioblastoma tumor xenografts. (United States)

    Johnson, Hannah; Del Rosario, Amanda M; Bryson, Bryan D; Schroeder, Mark A; Sarkaria, Jann N; White, Forest M


    Glioblastoma multiforme (GBM) is a malignant primary brain tumor with a mean survival of 15 months with the current standard of care. Genetic profiling efforts have identified the amplification, overexpression, and mutation of the wild-type (wt) epidermal growth factor receptor tyrosine kinase (EGFR) in ≈ 50% of GBM patients. The genetic aberration of wtEGFR is frequently accompanied by the overexpression of a mutant EGFR known as EGFR variant III (EGFRvIII, de2-7EGFR, ΔEGFR), which is expressed in 30% of GBM tumors. The molecular mechanisms of tumorigenesis driven by EGFRvIII overexpression in human tumors have not been fully elucidated. To identify specific therapeutic targets for EGFRvIII driven tumors, it is important to gather a broad understanding of EGFRvIII specific signaling. Here, we have characterized signaling through the quantitative analysis of protein expression and tyrosine phosphorylation across a panel of glioblastoma tumor xenografts established from patient surgical specimens expressing wtEGFR or overexpressing wtEGFR (wtEGFR+) or EGFRvIII (EGFRvIII+). S100A10 (p11), major vault protein, guanylate-binding protein 1(GBP1), and carbonic anhydrase III (CAIII) were identified to have significantly increased expression in EGFRvIII expressing xenograft tumors relative to wtEGFR xenograft tumors. Increased expression of these four individual proteins was found to be correlated with poor survival in patients with GBM; the combination of these four proteins represents a prognostic signature for poor survival in gliomas. Integration of protein expression and phosphorylation data has uncovered significant heterogeneity among the various tumors and has highlighted several novel pathways, related to EGFR trafficking, activated in glioblastoma. The pathways and proteins identified in these tumor xenografts represent potential therapeutic targets for this disease.

  4. Mapping of homozygous deletions in verified esophageal adenocarcinoma cell lines and xenografts. (United States)

    Boonstra, Jurjen J; van Marion, Ronald; Douben, Hannie J C W; Lanchbury, Jerry S; Timms, Kirsten M; Abkevich, Victor; Tilanus, Hugo W; de Klein, Annelies; Dinjens, Winand N M


    Human esophageal adenocarcinoma (EAC) cell lines and xenografts are powerful tools in the search for genetic alterations because these models are composed of pure human cancer cell populations without admixture of normal human cells. In particular detection of homozygous deletions (HDs) is easier using these pure populations of cancer cells. Identification of HDs could potentially lead to the subsequent identification of new tumor suppressor genes (TSGs) involved in esophageal adenocarcinogenesis. Genome wide single nucleotide polymorphism (SNP) arrays were used to identify HDs in 10 verified EAC cell lines and nine EAC xenografts. In total, 61 HDs (range 1-6 per sample) were detected and confirmed by polymerase chain reaction. Besides HDs observed in common fragile genomic regions (n = 26), and gene deserts (n = 8), 27 HDs were located in gene-containing regions. HDs were noted for known TSGs, including CDKN2A, SMAD4 and CDH3/CDH1. Twenty-two new chromosomal regions were detected harboring potentially new TSGs involved in EAC carcinogenesis. Two of these regions of homozygous loss, encompassing the ITGAV and RUNX1 gene, were detected in multiple samples indicating a potential role in the carcinogenesis of EAC. To exclude culturing artifacts, these last two deletions were confirmed by fluorescent in situ hybridization in the primary tumors of which the involved cell lines and xenografts were derived. In summary, in this report we describe the identification of HDs in a series of verified EAC cell lines and xenografts. The deletions documented here are a step forward identifying the key genes involved in EAC development.

  5. Benzyl Isothiocyanate Inhibits Epithelial-Mesenchymal Transition in Cultured and Xenografted Human Breast Cancer Cells


    Sehrawat, Anuradha; Singh, Shivendra V.


    We showed previously that cruciferous vegetable constituent benzyl isothiocyanate (BITC) inhibits growth of cultured and xenografted human breast cancer cells, and suppresses mammary cancer development in a transgenic mouse model. We now demonstrate, for the first time, that BITC inhibits epithelial-to-mesenchymal transition (EMT) in human breast cancer cells. Exposure of estrogen-independent MDA-MB-231 and estrogen-responsive MCF-7 human breast cancer cell lines and a pancreatic cancer cell ...

  6. Xenograft scaffold full-wrap reinforcement of Krackow achilles tendon repair. (United States)

    Wisbeck, Jacob M; Parks, Brent G; Schon, Lew C


    Standard 4-strand repair of Achilles tendon tears is effective, but additional strength may be desirable in patients who are compromised or those with reruptures. Use of a xenograft scaffold has not been investigated biomechanically in Achilles tendon repair. This study compared stiffness, gap formation, and ultimate load to failure with Krackow repair vs Krackow repair augmented with xenograft scaffold in 6 matched pairs of fresh-frozen human lower extremities. The Achilles tendon was transected 4 cm above the calcaneal insertion. Specimens were randomized to receive standard Krackow repair or Krackow repair augmented with a porcine xenograft scaffold. The graft was wrapped around the repaired tendon, sutured to itself with 2-0 FiberWire (Arthrex, Naples, Florida), and attached to the tendon distally and proximally and then medially and laterally. Specimens were loaded for 200 cycles between 5 and 30 N. Load to 5-mm gapping and load to ultimate failure were measured. Xenograft scaffold augmentation of standard Krakow Achilles tendon repair was significantly stronger and stiffer than standard Krackow repair in a biomechanical model immediately after repair (39.0±8.8 vs 24.4±4.6 N/mm; P=.01). The augmented repair group had significantly higher load to ultimate failure than did the Krackow group (862.7±174.0 vs 479.5±65.5 N; P<.01). Biological factors remain to be investigated, but this augmentation method could provide additional strength in patients who are compromised or those with reruptures.

  7. Antitumor activity and biodistribution of cisplatin nanocapsules in nude mice bearing human ovarian carcinoma xenografts


    Staffhorst, R.W.H.M.; Born, K.; Erkelens, C.A.M.; Hamelers, I.H.L.; Peters, G J; Boven, E.; de Kroon, A.I.P.M.


    Cisplatin nanocapsules represent a novel lipid formulation of the anticancer drug cis-diamminedichloridoplatinum(II) (cisplatin), characterized by an unprecedented cisplatin-tolipid molar ratio, and exhibiting strongly increased in-vitro cytotoxicity compared with the free drug. In this study, antitumor efficacy and biodistribution of PEGylated cisplatin nanocapsules were compared with those of the free drug in a mouse tumor model. Nude mice bearing human ovarian carcinoma OVCAR-3 xenografts ...

  8. A novel xenograft model in zebrafish for high-resolution investigating dynamics of neovascularization in tumors.

    Directory of Open Access Journals (Sweden)

    Chengjian Zhao

    Full Text Available Tumor neovascularization is a highly complex process including multiple steps. Understanding this process, especially the initial stage, has been limited by the difficulties of real-time visualizing the neovascularization embedded in tumor tissues in living animal models. In the present study, we have established a xenograft model in zebrafish by implanting mammalian tumor cells into the perivitelline space of 48 hours old Tg(Flk1:EGFP transgenic zebrafish embryos. With this model, we dynamically visualized the process of tumor neovascularization, with unprecedented high-resolution, including new sprouts from the host vessels and the origination from VEGFR2(+ individual endothelial cells. Moreover, we quantified their contributions during the formation of vascular network in tumor. Real-time observations revealed that angiogenic sprouts in tumors preferred to connect each other to form endothelial loops, and more and more endothelial loops accumulated into the irregular and chaotic vascular network. The over-expression of VEGF165 in tumor cells significantly affected the vascularization in xenografts, not only the number and size of neo-vessels but the abnormalities of tumor vascular architecture. The specific inhibitor of VEGFR2, SU5416, significantly inhibited the vascularization and the growth of melanoma xenografts, but had little affects to normal vessels in zebrafish. Thus, this zebrafish/tumor xenograft model not only provides a unique window to investigate the earliest events of tumoral neoangiogenesis, but is sensitive to be used as an experimental platform to rapidly and visually evaluate functions of angiogenic-related genes. Finally, it also offers an efficient and cost-effective means for the rapid evaluation of anti-angiogenic chemicals.

  9. Lidamycin Induces Apoptosis of B-Cell Lymphoma Cells and Inhibits Xenograft Growth in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    Hong Fang; Shenghua Zhang; Qingfang Miao; Dongsheng Xiong; Yongsu Zhen


    OBJECTIVE To study the cytotoxicity of Lidamycin (LDM) and its induction of apoptosis in Raji and Daudi cells of B-cell lymphoma, and the inhibition of growth of the lymphoma Raji xenograft in nude mice.METHODS MTT assay was used to observe the inhibition by LDM on the proliferation of the Raji and Daudi cells. Annexin V-FITC/PI double-stain, in combination with flow cytometry (FCM), was used to determine the induction of apoptosis by LDM in Raji cells. The B-cell lymphoma Raji xenograft model in nude mice was set up to detect the in vivo antitumor activity of LDM.RESULTS LDM markedly inhibited the proliferation of the Raji and Daudi cells in vitro, with IC50 values of 7.13×10-11 mol/L and 2.91×10-10 mol/L, respectively. The apoptotic rates of Raji cells were respectively 77.98% and 67.63% at 0.5 nmol/L and 0.25 nmol/L of LDM, indicating an obvious induction of apoptosis in Raji cells. LDM inhibited the formation and growth of human B-cell lymphoma Raji xenograft in nude mice. The inhibition rates of tumor growth were respectively 74.9% and 65.2% in LDM at dosage group of 0.05 mg/kg and 0.025 mg/kg, suggesting an apparent prolongation of survival time in the nude mouse bearing lymphoma.CONCLUSION LDM can effectively induce apoptosis of the B-cell lymphoma cells and inhibit the xenograft growth in nude mice.

  10. Canine distemper virus infection with secondary Bordetella bronchiseptica pneumonia in dogs


    HEADLEY, Selwyn Arlington; Graça,Dominguita Lühers; Costa,Mateus Matiuzzi da; Vargas,Agueda Castagna de


    Canine distemper virus infection and secondary Bordetella bronchiseptica pneumonia are described in mongrel dogs. Canine distemper was characterised by nonsuppurative demyelinating encephalitis with typical inclusion bodies in astrocytes. B. bronchiseptica was isolated from areas of purulent bronchopneumonia.

  11. Operculum bone carp (cyprinus carprio sp.) scaffold is a new potential xenograft material: a preliminary study (United States)

    Kartiwa, A.; Abbas, B.; Pandansari, P.; Prahasta, A.; Nandini, M.; Fadhlillah, M.; Subroto, T.; Panigoro, R.


    Orbital floor fracture with extensive bone loss, would cause herniation of the orbital tissue into the maxillary sinus. Graft implantation should be done on the orbital fracture with extensive bone loss. Different types of grafts have their own characteristics and advantages. Xenograft has been widely studied for use in bone defects. This study was to investigate cyprinus carprio sp. opercula bone as a potential xenograft. The aim of this study was to investigate based on EDS chemical analysis using a ZAF Standardless Method of Quantitative Analysis (Oxide) and SEM examination conducted in the laboratory of Mathematics, Institute of Technology Bandung. Particularly the mass ratio of Ca and P (5.8/3:47), the result is 1.67. This is equivalent to the stoichiometric Hydroxyapatite (HA) (Aoki H, 1991, Science and medical applications of hydroxyapatite, Tokyo: Institute for Medical and Engineering, Tokyo Medical and Dental University). C N O that there is an element of protein/amino acid collagen compound, serves as a matrix together with HA. As shown in the SEM analysis that the matrix is a porous sheet-shaped (oval) that interconnect with each other, which is good scaffold. The pore is composed of large pores >200 microns and smaller pores between the large pores with a size smaller or equal to 10 microns that can serve for the attachment of osteoblast cell. In conclusion, Opercula bone carp (cyprinus carprio sp.) scaffold could be a new potential xenograft material.

  12. Primary esophageal and gastro-esophageal junction cancer xenograft models: clinicopathological features and engraftment. (United States)

    Dodbiba, Lorin; Teichman, Jennifer; Fleet, Andrew; Thai, Henry; Sun, Bin; Panchal, Devang; Patel, Devalben; Tse, Alvina; Chen, Zhuo; Faluyi, Olusola O; Renouf, Daniel J; Girgis, Hala; Bandarchi, Bizhan; Schwock, Joerg; Xu, Wei; Bristow, Robert G; Tsao, Ming-Sound; Darling, Gail E; Ailles, Laurie E; El-Zimaity, Hala; Liu, Geoffrey


    There are very few xenograft models available for the study of esophageal (E) and gastro-esophageal junction (GEJ) cancer. Using a NOD/SCID model, we implanted 90 primary E and GEJ tumors resected from patients and six endoscopic biopsy specimens. Of 69 resected tumors with histologically confirmed viable adenocarcinoma or squamous cell carcinoma, 22 (32%) was engrafted. One of 11 tumors, considered to have had a complete pathological response to neo-adjuvant chemo-radiation, also engrafted. Of the 23 patients whose tumors were engrafted, 65% were male; 30% were early stage while 70% were late stage; 22% received neo-adjuvant chemo-radiation; 61% were GEJ cancers. Engraftment occurred in 18/54 (33%) adenocarcinomas and 5/16 (31%) squamous cell carcinomas. Small endoscopic biopsy tissue had a 50% (3/6) engraftment rate. Of the factors analyzed, pretreatment with chemo-radiation and well/moderate differentiation showed significantly lower correlation with engraftment (P<0.05). In the subset of patients who did not receive neo-adjuvant chemo-radiation, 18/41 (44%) engrafted compared with those with pretreatment where 5/29 (17%, P=0.02) engrafted. Primary xenograft lines may be continued through 4-12 passages. Xenografts maintained similar histology and morphological characteristics with only minor variations even after multiple passaging in most instances.

  13. Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry (United States)

    Fernández, Roberto; Garate, Jone; Lage, Sergio; Terés, Silvia; Higuera, Mónica; Bestard-Escalas, Joan; López, Daniel H.; Guardiola-Serrano, Francisca; Escribá, Pablo V.; Barceló-Coblijn, Gwendolyn; Fernández, José A.


    Xenografts are commonly used to test the effect of new drugs on human cancer. However, because of their heterogeneity, analysis of the results is often controversial. Part of the problem originates in the existence of tumor cells at different metabolic stages: from metastatic to necrotic cells, as it happens in real tumors. Imaging mass spectrometry is an excellent solution for the analysis of the results as it yields detailed information not only on the composition of the tissue but also on the distribution of the biomolecules within the tissue. Here, we use imaging mass spectrometry to determine the distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their plasmanyl- and plasmenylether derivatives (PC-P/O and PE-P/O) in xenografts of five different tumor cell lines: A-549, NCI-H1975, BX-PC3, HT29, and U-87 MG. The results demonstrate that the necrotic areas showed a higher abundance of Na+ adducts and of PC-P/O species, whereas a large abundance of PE-P/O species was found in all the xenografts. Thus, the PC/PC-ether and Na+/K+ ratios may highlight the necrotic areas while an increase on the number of PE-ether species may be pointing to the existence of viable tumor tissues. Furthermore, the existence of important changes in the concentration of Na+ and K+ adducts between different tissues has to be taken into account while interpreting the imaging mass spectrometry results.

  14. Metabolic response to everolimus in patient-derived triple negative breast cancer xenografts. (United States)

    Euceda, Leslie R; Hill, Deborah K; Stokke, Endre; Hatem, Rana; Botty, Rania El; Bièche, Ivan; Marangoni, Elisabetta; Bathen, Tone F; Moestue, Siver A


    Patients with triple negative breast cancer (TNBC) are unresponsive to endocrine and anti-HER2 pharmacotherapy, limiting their therapeutic options to chemotherapy. TNBC is frequently associated with abnormalities in the PI3K/AKT/mTOR signaling pathway; drugs targeting this pathway are currently being evaluated in these patients. However, response is variable, partly due to heterogeneity within TNBC, conferring a need to identify biomarkers predicting response and resistance to targeted therapy. In this study, we used a metabolomics approach to assess response to the mTOR inhibitor everolimus in a panel of TNBC patient-derived xenografts (PDX) (n=103 animals). Tumor metabolic profiles were acquired using high-resolution magic angle spinning magnetic resonance spectroscopy. Partial least squares-discriminant analysis on relative metabolite concentrations discriminated treated xenografts from untreated controls with an accuracy of 67% (p=0.003). Multilevel linear mixed-effects models (LMM) indicated reduced glycolytic lactate production and glutaminolysis after treatment, consistent with PI3K/AKT/mTOR pathway inhibition. Although inherent metabolic heterogeneity between different PDX models seemed to hinder prediction of treatment response, the metabolic effects following treatment were more pronounced in responding xenografts compared to non-responders. Additionally, the metabolic information predicted p53 mutation status, which may provide complimentary insight into the interplay between PI3K signaling and other drivers of disease progression.

  15. [Biomaterials for bone filling: comparisons between autograft, hydroxyapatite and one highly purified bovine xenograft]. (United States)

    Chappard, D; Zhioua, A; Grizon, F; Basle, M F; Rebel, A


    Bone grafts are becoming increasingly common in orthopaedics, neurosurgery and periodontology. Twenty one New Zealand rabbits were used in the present study comparing several materials usable as bone substitutes. A 4.5 mm hole was drilled in the inner femoral condyles. Holes were filled with either an autograft (from the opposite condyle), an hydroxylapatite (Bioapatite), or a highly purified bovine xenograft (T650 Lubboc). Animals were sacrificed at 1, 3 and 6 months post implantation and a quantitative analysis of newly-formed bone volume (BNF/IV) and remaining biomaterials (BMAT/IV) was done. In addition, some holes were left unfilled and served as controls. At 6 months, there was no tendency for spontaneous repair in the control animals. The autografted animals have repaired their trabecular mass and architecture within the first month. Hydroxylapatite appeared unresorbed at six months and only thin and scanty new trabeculae were observed. The xenograft induced woven bone trabeculae formation on the first month. This was associated with resorption of the material by two multinucleated cell populations. At six months, the epiphyseal architecture was restored and the biomaterial has disappeared in most cases. Xenografts appear a promising alternative to autografts and allografts, whose infectious risks and ethical problems should always be borne in mind.

  16. Canine detection of free-ranging brown treesnakes on Guam (United States)

    Savidge, J.A.; Stanford, J.W.; Reed, R.N.; Haddock, G.R.; Adams, A.A.Y.


    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.

  17. A compendium of canine normal tissue gene expression.

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    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.

  18. The anti-canine distemper virus activities of ex vivo-expanded canine natural killer cells. (United States)

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


    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.

  19. Severe cases of ectopically erupting maxillary canine with excessive mesial angulation


    Taguchi, Yo; Hayashi-Sakai, Sachiko; TSUDA, takashi


    The aim of the present study was to examine retrospectively how best to treat severe cases of ectopically erupting maxillary canines with mesial angulation exceeding 50 degrees. From the ectopically erupting canines diagnosed at the Pediatric Dental Clinic of Niigata University Hospital, we selected for our study 14 severe cases in which mesial angulation exceeded 50 degrees. Nine ectopically erupting canines could be aligned within the arch after traction, and two canines are in the course o...

  20. Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin

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    Jakobsen Maria


    Full Text Available Abstract Background Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα, interleukin-12 (IL-12, and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs. Methods Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels. Results Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by

  1. Maxillary canine transpositions in two brothers and one sister: associated dental anomalies and genetic basis. (United States)

    Segura, Juan J; Hattab, Faiez; Ríos, Vicente


    Transposition is an uncommon dental anomaly involving positional interchange of two teeth. The maxillary canine is the tooth more frequently transposed in man. Maxillary canine-first premolar appears to be the most common type of tooth transposition, followed by maxillary canine-lateral incisor transposition. Maxillary canine transpositions are frequently associated with other dental abnormalities such as agenesis and pegshaped incisors. This report describes the presence of transposed canines in one sister and two brothers. The female showed bilateral maxillary canine-first premolar transposition with the left canine fully mesial to its neighboring first premolar, and the right canine blocked-out facially between the first and second premolar. One of the brothers showed full maxillary left canine-lateral incisor transposition. The other brother showed maxillary canine-first premolar transposition and agenesis of maxillary lateral incisors, with the left canine blocked-out facially between the first and second premolar. Findings from this case report and other previously published cases provide strong evidence that maxillary canine transpositions are a disturbance of tooth order and eruptive position resulting from genetic influences within a multifactorial inheritance model.

  2. Eliminating canine rabies: the role of public-private partnerships. (United States)

    Taylor, Louise


    Canine rabies has been eliminated from industrialized countries, but infected dogs remain the principal source of human infections in the developing world. Despite the availability of effective tools for prevention and post-exposure prophylaxis, canine rabies inflicts a heavy burden on the poorest people of Africa, Asia and Latin America, resulting in more than 60,000 deaths each year. Public-private partnerships offer a new approach to the challenge of eliminating canine rabies in the developing world, by bringing together stakeholders to share responsibilities and reduce costs. The leading partnership for rabies control, the Partners for Rabies Prevention, is an informal international group that includes representatives of major health organizations (WHO, PAHO, FAO, OIE), the European Commission, universities, nongovernmental organizations, the human and animal health industries, and private global health institutions. This article describes how the Partners for Rabies Prevention is working toward the global elimination of canine rabies. It forms part of a symposium in Antiviral Research on the elimination of canine rabies.

  3. Serum canine pancreatic lipase immunoreactivity in experimentally induced and naturally occurring canine monocytic ehrlichiosis (Ehrlichia canis). (United States)

    Mylonakis, Mathios E; Xenoulis, Panagiotis G; Theodorou, Konstantina; Siarkou, Victoria I; Steiner, Jörg M; Harrus, Shimon; Leontides, Leonidas; Rallis, Timoleon; Suchodolski, Jan S; Koutinas, Christos K; Koutinas, Alexander F


    Ehrlichia canis infection causes multisystemic disease in dogs (canine monocytic ehrlichiosis, CME) which is associated with variable morbidity and mortality. Atypical clinical manifestations, including gastrointestinal signs, may occasionally occur in CME and approximately 10-15% of dogs are presented with historical or clinical evidence of vomiting, diarrhea, and/or abdominal discomfort. The objective of this study was to investigate if there are any alterations in serum canine pancreatic lipase immunoreactivity (cPLI) in dogs with experimentally induced or naturally occurring monocytic ehrlichiosis. Serum samples from 10 Beagle dogs experimentally infected with E. canis and two healthy uninfected Beagles were serially examined; samples from 20 naturally infected dogs (10 with non-myelosuppressive [NME] and 10 with myelosuppressive [ME] ehrlichiosis) were also examined at a given point in time (cross-sectional sampling). None of the experimentally infected Beagles showed gastrointestinal signs or increased cPLI concentrations prior to or following the artificial infection. Three naturally infected dogs with NME and one with ME demonstrated serum cPLI concentrations in the diagnostic range for pancreatitis (>400 μg/L) without showing gastrointestinal signs. The results of the present study indicated that 4/20 (20%) of dogs naturally infected with E. canis demonstrated increased serum cPLI concentrations consistent with mild and clinically inapparent pancreatitis.

  4. Effects of the canine rattlesnake vaccine in moderate to severe cases of canine crotalid envenomation

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    Leonard MJ


    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. Soluble Form of Canine Transferrin Receptor Inhibits Canine Parvovirus Infection In Vitro and In Vivo

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    Jiexia Wen


    Full Text Available Canine parvovirus (CPV disease is an acute, highly infectious disease threatening the dog-raising industry. So far there are no effective therapeutic strategies to control this disease. Although the canine transferrin receptor (TfR was identified as a receptor for CPV infection, whether extracellular domain of TfR (called soluble TfR (sTfR possesses anti-CPV activities remains elusive. Here, we used the recombinant sTfR prepared from HEK293T cells with codon-optimized gene structure to investigate its anti-CPV activity both in vitro and in vivo. Our results indicated that codon optimization could significantly improve sTfR expression in HEK293T cells. The prepared recombinant sTfR possessed a binding activity to both CPV and CPV VP2 capsid proteins and significantly inhibited CPV infection of cultured feline F81 cells and decreased the mortality of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity both in vitro and in vivo.

  6. Soluble form of canine transferrin receptor inhibits canine parvovirus infection in vitro and in vivo. (United States)

    Wen, Jiexia; Pan, Sumin; Liang, Shuang; Zhong, Zhenyu; He, Ying; Lin, Hongyu; Li, Wenyan; Wang, Liyue; Li, Xiujin; Zhong, Fei


    Canine parvovirus (CPV) disease is an acute, highly infectious disease threatening the dog-raising industry. So far there are no effective therapeutic strategies to control this disease. Although the canine transferrin receptor (TfR) was identified as a receptor for CPV infection, whether extracellular domain of TfR (called soluble TfR (sTfR)) possesses anti-CPV activities remains elusive. Here, we used the recombinant sTfR prepared from HEK293T cells with codon-optimized gene structure to investigate its anti-CPV activity both in vitro and in vivo. Our results indicated that codon optimization could significantly improve sTfR expression in HEK293T cells. The prepared recombinant sTfR possessed a binding activity to both CPV and CPV VP2 capsid proteins and significantly inhibited CPV infection of cultured feline F81 cells and decreased the mortality of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity both in vitro and in vivo.

  7. Canine Oral Eosinophilic Granuloma Treated with Electrochemotherapy

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    Matías Nicolás Tellado


    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.

  8. [Diagnostic tools for canine parvovirus infection]. (United States)

    Proksch, A L; Hartmann, K


    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.

  9. Genotyping of Canine parvovirus in western Mexico. (United States)

    Pedroza-Roldán, César; Páez-Magallan, Varinia; Charles-Niño, Claudia; Elizondo-Quiroga, Darwin; De Cervantes-Mireles, Raúl Leonel; López-Amezcua, Mario Alberto


    Canine parvovirus (CPV) is one of the most common infectious agents related to high morbidity rates in dogs. In addition, the virus is associated with severe gastroenteritis, diarrhea, and vomiting, resulting in high death rates, especially in puppies and nonvaccinated dogs. To date, there are 3 variants of the virus (CPV-2a, CPV-2b, and CPV-2c) circulating worldwide. In Mexico, reports describing the viral variants circulating in dog populations are lacking. In response to this deficiency, a total of 41 fecal samples of suspected dogs were collected from October 2013 through April 2014 in the Veterinary Hospital of the University of Guadalajara in western Mexico. From these, 24 samples resulted positive by polymerase chain reaction, and the viral variant was determined by restriction fragment length polymorphism. Five positive diagnosed samples were selected for partial sequencing of the vp2 gene and codon analysis. The results demonstrated that the current dominant viral variant in Mexico is CPV-2c. The current study describes the genotyping of CPV strains, providing valuable evidence of the dominant frequency of this virus in a dog population from western Mexico.

  10. Haematological and biochemical analysis in canine enteritis

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    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

  11. Transmembrane potentials of canine AV junctional tissues. (United States)

    Tse, W W


    The atrioventricular (AV) junction comprises the AV node, His bundle (HB), and specialized tissues proximal to the node called paranodal fibers (PNF). In the present study, an in vitro, dissection-exposed canine right atrial (RA), transitional fiber (TF), AV junctional preparation was used. The TF and PNF formed a pathway running along the base of the septal cusp of the tricuspid valve (SCTV). In the first experiment, impulses elicited at the RA were monitored to propagate sequentially through the TF, PNF, AV node, and then the HB. This functional evidence supports the concept that a conduction pathway connecting the RA and the AV node exists along the base of the SCTV. This internodal pathway is referred to as the septal cusp pathway. In another experiment, transmembrane potentials and Vmax were determined on each of the AV junctional tissues. Results showed that PNF had the lowest Vmax (2.5 V/sec), followed by AV node (7.0 V/sec) and HB (33 V/sec). This finding showed that PNF, and not the AV node, has the lowest Vmax, suggesting that the PNF has the lowest conductivity among the AV junctional tissues, and this study advances our understanding on the mechanism of AV conduction delay in dog hearts.

  12. Nodular Epiescleritis Granulomatous Canine. Case Report

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    Camilo Guarín Patarroyo


    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.

  13. Quantification of Zolpidem in Canine Plasma

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    Mario Giorgi


    Full Text Available Problem statement: Zolpidem is a non-benzodiazepine hypnotic agent currently used in human medicine. In contrast to benzodiazepines, zolpidem preferentially binds with the GABAA complex ϖ receptors while poorly interacting with the other ϖ receptor complexes. Recent studies have suggested that ZP may be used to initiate sedation and diminish severe anxiety responses in dogs. The aim of the present study is to develop and validate a new HPLC-FL based method to quantify zolpidem in canine plasma. Approach: Several parameters both in the extraction and in the detection method were evaluated. The applicability of the method was determined by administering zolpidem to one dog. Results: The final mobile phase was acetonitrile: KH2PO4 (15 mM; pH 6.0 40:60 v/v, with a flow rate of 1 mL min-1 and excitation and emission wave lengths of 254 and 400 nm, respectively. The best extraction solvent was CH2Cl2:Et2O (3:7 v/v, this gave recoveries ranging from 83-95%. The limit of quantification was 1 ng mL-1. The chromatographic runs were specific with no interfering peaks at the retention times of the analyte. The other validation parameters were in agreement with the EMEA. Conclusion/Recommendations: This method (extraction, separation and applied techniques is simple and effective. This technique may have applications for pharmacokinetic or toxicological studies.

  14. Establishment of sexual dimorphism in north indian population by odontometric study of permanent maxillary canine teeth

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    Shalini Gupta


    Full Text Available Aim: To investigate whether sexual dimorphism can be established by odontometric study of permanent maxillary canine teeth as well as inter-canine width in north Indian population. Study Design: The study was carried out at department of oral and maxillofacial pathology, King George′s Medical University, Lucknow, India on students and patients reporting at OPD. Out of total 180 subjects examined 90 subjects were female and 90 were male. Impressions of the upper arch were made using alginate and casts poured in dental stone. The mesiodistal diameter (MD of the crown of permanent maxillary canine both on right and left sides and inter-canine width were measured. From these measurements, maxillary canine index was calculated. The percentage of sexual dimorphism (SD was assessed for all the parameters. Results: In the present study, the MD of maxillary canine for both right (P = 0.001 and left side (P = 0.005 was significantly higher among male subjects than females, Similar observation was found for inter-canine width too (P = 0.0001. However, the maxillary canine index for right and left was almost similar (P > 0.05 for both male and female subjects. The SD in right and left MDs of maxillary canine was 4.2% and 3.6% respectively. For, inter-canine width it was maximum (13.7%. However, SD in right and left canine index showed negative values (−2.1% and -0.9% respectively. Conclusion: There was SD in MD and inter-canine width of permanent maxillary canine teeth. SD was more on right permanent maxillary canine teeth than left permanent maxillary canine.

  15. Finite element analysis of rapid canine retraction through reducing resistance and distraction

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    Junjie XUE


    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.

  16. Chromosomal assignment of canine THADA gene to CFA 10q25

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    Dolf Gaudenz


    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

  17. Radiation Response Modulation of GW572016 (EGFR/HER2 Dual Tyrosine Kinase Inhibitor) in Human Breast Cancer Xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yeon Sil; Roh, Kwang Won; Chae, Soo Min; Yoon, Sei Chul; Jang, Hong Seok; Chung, Su Mi [The Catholic University of Korea, College of Medicine, Seoul (Korea, Republic of); Mun, Seong Kwon [Eulji University Hospital, Daejeon (Korea, Republic of)


    Purpose: We examined the effect of the dual EGFR/HER2 tyrosine kinase inhibitor, GW572016, on EGFR/HER2 receptor phosphorylation, inhibition of downstream signaling and radiosensitization in either an EGFR or HER2 overexpressing human breast cancer xenograft. Materials and Methods: We established SCID mice xenografts from 4 human breast cancer cell line that overexpressed EGFR or HER 2 (SUM 102, SUM 149, SUM 185, SUM 225). Two series of xenografts were established. One series was established for determining inhibition of the EGFR/HER2 receptor and downstream signaling activities by GW572016. The other series was established for determining the radiosensitization effect of GW572016. Inhibition of the receptor and downstream signaling proteins were measured by the use of immunoprecipitation and Western blotting. For determining the in vivo radiosensitization effect of GW572016, we compared tumor growth delay curves in the following four treatment arms: a) control; b) GW572016 alone; c) radiotherapy (RT) alone; d) GW572016 and RT. Results: GW572016 inhibited EGFR, HER2 receptor phosphorylation in SUM 149 and SUM 185 xenografts. In addition, the p44/42 MAPK (ERK 1/2) downstream signaling pathway was inactivated by GW572016 in the SUM 185 xenograft. In the SUM 225 xenograft, we could not observe inhibition of HER2 receptor phosphorylation by GW572016; both p44/42 MAPK (Erk1/2) and Akt downstream signal protein phosphorylation were inhibited by GW572016. GW572016 inhibited growth of the tumor xenograft of SUM 149 and SUM 185. The combination of GW572016 and RT enhanced growth inhibition greater than that with GW572016 alone or with RT alone in the SUM 149 xenograft. GW572016 appears to act as an in vivo radiosensitizer. Conclusion: GW572016 inhibited EGFR/HER2 receptor phosphorylation and downstream signaling pathway proteins. GW572016 modestly inhibited the growth of tumor in the SUM 185 xenograft and showed radiosensitization in the SUM 149 xenograft. Our results

  18. Comparative mapping of canine and human proximal Xq and genetic analysis of canine X-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Deschenes, S.M.; Puck, J.M.; Dutra, A.S. [Univ. of Pennsylvania School of Medicine and Children`s Hospital of Philadelphia, PA (United States)] [and others


    Parallel genetic analysis of animal and human genetic diseases can facilitate the identification and characterization of the causative gene defects. For example, canine X-linked severe combined immunodeficiency (SCID) is characterized by clinical, pathological, and immunological manifestations similar to the most common form of human SCID. To derive a canine syntenic map including genes that in humans are located in proximal Xq, near human X-linked SCID, poly (TG) polymorphisms were identified at the canine phosphoglycerate kinase (PGK) and choroideremia (CHM) loci. These plus a polymorphic poly (CAG) sequence in exon 1 of the canine androgen receptor gene (AR) were used to genotype members of the colony informative for X-linked SCID. No recombinations among SCIDX1, AR, PGK, or CHM were observed. Fluorescence in situ hybridization localized PGK and CHM to proximal Xq in the dog, in the same chromosomal location occupied by the human genes. Somatic cell hybrid analysis and methylation differences at AR demonstrated that female dogs carrying X-linked SCID have the same lymphocyte-limited skewed X-chromosome inactivation patterns as human carriers. These genetic and phenotypic findings provide evidence that mutations in the same gene, now identified as the {gamma} chain of the IL-2 receptor, cause canine and human X-linked SCID. This approach is an efficient method for comparative gene mapping and disease identification. 35 refs., 4 figs., 1 tab.

  19. 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))


    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.

  20. Complex odontoma associated to a primary maxillary canine: case report

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    Estela Maris LOSSO


    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.

  1. Orthodontic-surgical treatment of bilateral maxillary canine impaction

    Directory of Open Access Journals (Sweden)



    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.

  2. Glucosamine and chondroitin use in canines for osteoarthritis: A review. (United States)

    Bhathal, Angel; Spryszak, Meredith; Louizos, Christopher; Frankel, Grace


    Osteoarthritis is a slowly progressive and debilitating disease that affects canines of all breeds. Pain and decreased mobility resulting from osteoarthritis often have a negative impact on the affected canine's quality of life, level of comfort, daily functioning, activity, behaviour, and client-pet companionship. Despite limited and conflicting evidence, the natural products glucosamine hydrochloride (HCl) and chondroitin sulfate are commonly recommended by veterinarians for treating osteoarthritis in dogs. There is a paucity of well-designed clinical veterinary studies investigating the true treatment effect of glucosamine and chondroitin. The purposes of this review article are to provide a brief background on glucosamine and chondroitin use in canine osteoarthritis and to critically review the available literature on the role of these products for improving clinical outcomes. Based on critical review, recommendations for practice are suggested and a future study design is proposed.

  3. Canine tip wear in male and female anthropoids. (United States)

    Greenfield, L O


    One component of the "dual selection hypothesis" (Greenfield [1992a] Year. Phys. Anthropol. 35:153-185) is that the tips of female canines are commonly blunted and more frequently so than those of conspecific males. Data derived from two randomly selected age-graded samples of Macaca fascicularis (n = 70) and Colobus badius (n = 59) show that at least 80% of the females exhibit tip blunting on one or both canines and that frequencies of blunting are far greater than those of conspecific males in both jaws. Sexual dimorphism in mandibular canine morphology and wear and other recently critiqued aspects of the "dual selection hypothesis" (Plavcan and Kelley [1996] Am. J. Phys. Anthropol. 99:379-387.) are also discussed.

  4. Assessment of canine neonatal viability-the Apgar score. (United States)

    Veronesi, M C


    Perinatal mortality is relatively high in dogs, with deaths peaking around the time of birth and during the first week of age. Among the several causes of canine perinatal mortality, whelping is the greatest cause. Therefore, early neonatal assistance at birth should be mandatory with dogs. In comparison with human neonatology, knowledge and technological ability in canine neonatology is tremendously scarce. The Apgar score for the newborn viability assessment at birth represents a feasible method for the prompt recognition of newborns that will need special assistance immediately after birth. The five parameters of the Apgar score were adapted to the canine species by different studies. Advantages and limits, as well as clinical applications, are presented and discussed in further detail. It was concluded that the Apgar score represents the easiest and simplest, non-invasive and reliable method, that could be performed under every clinical and practical condition, for newborn puppies viability evaluations and short-term survival prognosis.

  5. Characterization of canine platelet adhesion to extracellular matrix proteins. (United States)

    Pelagalli, Alessandra; Pero, Maria Elena; Mastellone, Vincenzo; Cestaro, Anna; Signoriello, Simona; Lombardi, Pietro; Avallone, Luigi


    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.

  6. Severe canine distemper outbreak in unvaccinated dogs in Mozambique. (United States)

    Zacarias, Julieta; Dimande, Alberto; Achá, Sara; Dias, Paula T; Leonel, Elisa M; Messa, Aurora; Macucule, Baltazar; Júnior, José L; Bila, Custódio G


    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.

  7. Immunopathogenic and Neurological Mechanisms of Canine Distemper Virus

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    Otávio Valério Carvalho


    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.

  8. Cellular endocytic compartment localization of expressed canine CD1 molecules

    DEFF Research Database (Denmark)

    Schjærff, Mette; Keller, Stefan M.; Affolter, Verena K.


    CD1 molecules are glycoproteins present primarily on dendritic cells (DCs), which recognize and presenta variety of foreign- and self-lipid antigens to T-cells. Humans have five different CD1 isoforms that sur-vey distinct cellular compartments allowing for recognition of a large repertoire...... onlya diminished GFP expression. In conclusion, canine CD1 transfectants show distinct localization patternsthat are similar to human CD1 proteins with the exception of the canine CD1d isoform, which most likelyis non-functional. These findings imply that canine CD1 localization overall resembles human...... CD1 traf-ficking patterns. This knowledge is important for the understanding of lipid antigen-receptor immunityin the dog....

  9. Feline and Canine Coronaviruses: Common Genetic and Pathobiological Features

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    Sophie Le Poder


    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.

  10. Management of impacted all canines with surgical exposure and alignment by orthodontic treatment

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    Radha Katiyar


    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.

  11. Diagnosis of canine monocytotropic ehrlichiosis (Ehrlichia canis): an overview. (United States)

    Harrus, Shimon; Waner, Trevor


    Canine monocytotropic ehrlichiosis (CME), caused by the rickettsia Ehrlichia canis, an important canine disease with a worldwide distribution. Diagnosis of the disease can be challenging due to its different phases and multiple clinical manifestations. CME should be suspected when a compatible history (living in or traveling to an endemic region, previous tick exposure), typical clinical signs and characteristic hematological and biochemical abnormalities are present. Traditional diagnostic techniques including hematology, cytology, serology and isolation are valuable diagnostic tools for CME, however a definitive diagnosis of E. canis infection requires molecular techniques. This article reviews the current literature covering the diagnosis of infection caused by E. canis.

  12. Sphingomyelin induces structural alteration in canine parvovirus capsid


    Pakkanen, Kirsi; Karttunen, Jenni; Virtanen, Salla; Vuento, Matti


    One of the essential steps in canine parvovirus (CPV) infection, the release from endosomal vesicles, is dominated by interactions between the virus capsid and the endosomal membranes. In this study, the effect of sphingomyelin and phosphatidyl serine on canine parvovirus capsid and on the phospholipase A2 (PLA2) activity of CPV VP1 unique N-terminus was analyzed. Accordingly, a significant (P ≤ 0.05) shift of tryptophan fluorescence emission peak was detected at pH 5.5 in the presen...

  13. BSAVA Manual of Canine and Feline Musculoskeletal Imaging

    DEFF Research Database (Denmark)

    This, the second edition of the BSAVA Manual of Canine and Feline Musculoskeletal Imaging, has been extensively updated reflecting the dramatic changes that have taken place in radiography over the past 10 years. With the increasing availability of digital radiography in general veterinary practice...... of the manual makes it ideal for use in general practice as well as being a rich source of information for students and newly qualified veterinary surgeons. However, the depth of information supplied by an international panel of authors makes the BSAVA Manual of Canine and Feline Musculoskeletal Imaging second...

  14. Canine distemper spillover in domestic dogs from urban wildlife. (United States)

    Kapil, Sanjay; Yeary, Teresa J


    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.

  15. FDG PET/CT imaging in canine cancer patients

    DEFF Research Database (Denmark)

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


    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...

  16. MicroRNA-214 and MicroRNA-126 Are Potential Biomarkers for Malignant Endothelial Proliferative Diseases

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    Kazuki Heishima


    Full Text Available Malignant endothelial proliferative diseases including human angiosarcoma (AS and canine hemangiosarcoma (HSA are serious diseases with a grave prognosis. Establishing liquid biopsy-based biomarkers for screening has definite clinical utility; however, plasma miRNAs up- or down-regulated in these sarcomas have been unclear. For identifying possible diagnostic plasma miRNAs for these sarcomas, we investigated whether plasma miR-214 and miR-126, which miRNAs play important roles in angiogenesis and tumorigenesis, were elevated in malignant endothelial proliferative diseases. For this investigation, human angiosarcoma and canine hemangiosarcoma cell lines and clinical plasma samples of canine hemangiosarcoma were examined by performing miRNA qRT-PCR. We report here that human angiosarcoma and canine hemangiosarcoma cell lines over-secreted miR-214 and miR-126 via microvesicles; in addition, their levels in the plasma samples from canines with hemangiosarcoma were increased. Moreover, the surgical resection of primary tumors decreased the levels of plasma miR-214 and miR-126. Our findings suggest that these malignant endothelial proliferative diseases over-secreted miR-214 and miR-126, thus suggesting that these miRNAs have potential as diagnostic biomarkers for malignant endothelial proliferative diseases in canine and possible in human angiosarcoma.

  17. Erlotinib pretreatment improves photodynamic therapy of non-small cell lung carcinoma xenografts via multiple mechanisms (United States)

    Gallagher-Colombo, Shannon M.; Miller, Joann; Cengel, Keith A.; Putt, Mary E.; Vinogradov, Sergei A.; Busch, Theresa M.


    Aberrant expression of the epidermal growth factor receptor (EGFR) is a common characteristic of many cancers including non-small cell lung carcinoma (NSCLC), head and neck squamous cell carcinoma, and ovarian cancer. While EGFR is currently a favorite molecular target for treatment of these cancers, inhibition of the receptor with small molecule inhibitors (i.e.- erlotinib) or monoclonal antibodies (i.e.- cetuximab) does not provide long-term therapeutic benefit as standalone treatment. Interestingly, we have found that addition of erlotinib to photodynamic therapy (PDT) can improve treatment response in typically erlotinib-resistant NSCLC tumor xenografts. Ninety-day complete response rates of 63% are achieved when erlotinib is administered in three doses before PDT of H460 human tumor xenografts, compared to 16% after PDT-alone. Similar benefit is found when erlotinib is added to PDT of A549 NCSLC xenografts. Improved response is accompanied by increased vascular shutdown, and erlotinib increases the in vitro cytotoxicity of PDT to endothelial cells. Tumor uptake of the photosensitizer (benzoporphyrin derivative monoacid ring A; BPD) is increased by the in vivo administration of erlotinib; nevertheless, this elevation of BPD levels only partially accounts for the benefit of erlotinib to PDT. Thus, pretreatment with erlotinib augments multiple mechanisms of PDT effect that collectively lead to large improvements in therapeutic efficacy. These data demonstrate that short-duration administration of erlotinib before PDT can greatly improve the responsiveness of even erlotinib-resistant tumors to treatment. Results will inform clinical investigation of EGFR-targeting therapeutics in conjunction with PDT. PMID:26054596

  18. Analysis of the anti-tumor effect of cetuximab using protein kinetics and mouse xenograft models

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    Matsuo Teppei


    Full Text Available Abstract Background The binding of EGFR and its ligands leads to autophosphorylation of receptor tyrosine kinase as well as subsequent activation of signal transduction pathways that are involved in regulating cellular proliferation, differentiation, and survival. An EGFR inhibitor, cetuximab binds to EGFR and consequently blocks a variety of cellular processes. KRAS/BRAF mutations are known to be associated with a low response rate to cetuximab. In the present study, to clarify the anti-tumor mechanisms of cetuximab, we evaluated the KRAS/BRAF status, phosphorylation level of the EGFR pathway, and the tumor suppression effect in vivo, using a human colon cancer cell line HT29, which exhibited the highest EGFR expression in response to the cetuximab therapy among the 6 colorectal cancer cell lines tested. Findings The conventional growth suppression assay did not work efficiently with cetuximab. EGF, TGF-α, and IGF activated the EGFR/MAPK cell signaling pathway by initiating the phosphorylation of EGFR. Cetuximab partially inhibited the EGFR/MAPK pathway induced by EGF, TGF-α, and IGF. However, cetuximab exposure induced the EGFR, MEK, and ERK1/2 phosphorylation by itself. Mouse xenograft tumor growth was significantly inhibited by cetuximab and both cetuximab-treated and -untreated xenograft specimens exhibited phosphorylations of the EGFR pathway proteins. Conclusions We have confirmed that cetuximab inhibited the EGFR/MAPK pathway and reduced tumor growth in the xenografts while the remaining tumor showed EGFR pathway activation. These results suggest that: ( i The effect of cetuximab in growth signaling is not sufficient to induce complete growth suppression in vitro; ( ii time-course monitoring may be necessary to evaluate the effect of cetuximab because EGFR signaling is transmitted in a minute order; and ( iii cetuximab treatment may have cells acquired resistant selectively survived in the heterogeneous cancer population.

  19. Hepatocellular carcinoma xenograft supports HCVreplication: A mouse model for evaluating antivirals

    Institute of Scientific and Technical Information of China (English)

    Sidhartha Hazari; Henry J Hefler; Partha K Chandra; Bret Poat; Feyza Gunduz; Tara Ooms; Tong Wu; Luis A Balart; Srikanta Dash


    AIM: To develop a hepatocellular carcinoma (HCC) xenograft model for studying hepatitis C virus (HCV) replication in a mice, and antiviral treatment.METHODS: We developed a stable S3-green fluorescence protein (GFP) cell line that replicated the GFPtagged HCV sub-genomic RNA derived from a highlyefficient JFH1 virus. S3-GFP replicon cell line was injected subcutaneously into γ-irradiated SCID mice. We showed that the S3-GFP replicon cell line formed humanHCC xenografts in SCID mice. Cells were isolated from subcutaneous tumors and then serially passaged multiple times in SCID mice by culturing in growth medium supplemented with G-418. The mouse-adapted S3-GFP replicon cells were implanted subcutaneously and also into the liver of SCID mice via intrasplenic infusion to study the replication of HCV in the HCC xenografts. The tumor model was validated for antiviral testing after intraperitoneal injection of interferon-α (IFN-α).RESULTS: A highly tumorigenic S3-GFP replicon cell line was developed that formed subcutaneous tumors within 2 wk and diffuse liver metastasis within 4 wkin SCID mice. Replication of HCV in the subcutaneous and liver tumors was confirmed by cell colony assay, detection of the viral RNA by ribonuclease protectionassay and real-time quantitative reverse transcription polymerase chain reaction. High-level replication of HCV sub-genomic RNA in the tumor could be visualized by GFP expression using fluorescence microscopy. IFN-α cleared HCV RNA replication in the subcutaneous tumors within 2 wk and 4 wk in the liver tumor model.

  20. Developmental exposure to estrogen alters differentiation and epigenetic programming in a human fetal prostate xenograft model.

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    Camelia M Saffarini

    Full Text Available Prostate cancer is the most frequent non-cutaneous malignancy in men. There is strong evidence in rodents that neonatal estrogen exposure plays a role in the development of this disease. However, there is little information regarding the effects of estrogen in human fetal prostate tissue. This study explored early life estrogen exposure, with and without a secondary estrogen and testosterone treatment in a human fetal prostate xenograft model. Histopathological lesions, proliferation, and serum hormone levels were evaluated at 7, 30, 90, and 200-day time-points after xenografting. The expression of 40 key genes involved in prostatic glandular and stromal growth, cell-cycle progression, apoptosis, hormone receptors and tumor suppressors was evaluated using a custom PCR array. Epigenome-wide analysis of DNA methylation was performed on whole tissue, and laser capture-microdissection (LCM isolated epithelial and stromal compartments of 200-day prostate xenografts. Combined initial plus secondary estrogenic exposures had the most severe tissue changes as revealed by the presence of hyperplastic glands at day 200. Gene expression changes corresponded with the cellular events in the KEGG prostate cancer pathway, indicating that initial plus secondary exposure to estrogen altered the PI3K-Akt signaling pathway, ultimately resulting in apoptosis inhibition and an increase in cell cycle progression. DNA methylation revealed that differentially methylated CpG sites significantly predominate in the stromal compartment as a result of estrogen-treatment, thereby providing new targets for future investigation. By using human fetal prostate tissue and eliminating the need for species extrapolation, this study provides novel insights into the gene expression and epigenetic effects related to prostate carcinogenesis following early life estrogen exposure.

  1. Primary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma.

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    Viviana P Montecinos

    Full Text Available Characterization of the mechanism(s of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP tissue that occurs between Days 6-14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen-mediated up-regulation of VEGF-A expression in the stromal compartment. The neo-vessel network anastomosed to the host mouse vascular system between Days 6-10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts.

  2. Erlotinib Pretreatment Improves Photodynamic Therapy of Non-Small Cell Lung Carcinoma Xenografts via Multiple Mechanisms. (United States)

    Gallagher-Colombo, Shannon M; Miller, Joann; Cengel, Keith A; Putt, Mary E; Vinogradov, Sergei A; Busch, Theresa M


    Aberrant expression of the epidermal growth factor receptor (EGFR) is a common characteristic of many cancers, including non-small cell lung carcinoma (NSCLC), head and neck squamous cell carcinoma, and ovarian cancer. Although EGFR is currently a favorite molecular target for the treatment of these cancers, inhibition of the receptor with small-molecule inhibitors (i.e., erlotinib) or monoclonal antibodies (i.e., cetuximab) does not provide long-term therapeutic benefit as standalone treatment. Interestingly, we have found that addition of erlotinib to photodynamic therapy (PDT) can improve treatment response in typically erlotinib-resistant NSCLC tumor xenografts. Ninety-day complete response rates of 63% are achieved when erlotinib is administered in three doses before PDT of H460 human tumor xenografts, compared with 16% after PDT-alone. Similar benefit is found when erlotinib is added to PDT of A549 NCSLC xenografts. Improved response is accompanied by increased vascular shutdown, and erlotinib increases the in vitro cytotoxicity of PDT to endothelial cells. Tumor uptake of the photosensitizer (benzoporphyrin derivative monoacid ring A; BPD) is increased by the in vivo administration of erlotinib; nevertheless, this elevation of BPD levels only partially accounts for the benefit of erlotinib to PDT. Thus, pretreatment with erlotinib augments multiple mechanisms of PDT effect that collectively lead to large improvements in therapeutic efficacy. These data demonstrate that short-duration administration of erlotinib before PDT can greatly improve the responsiveness of even erlotinib-resistant tumors to treatment. Results will inform clinical investigation of EGFR-targeting therapeutics in conjunction with PDT.

  3. Bone marrow CFU-GM and human tumor xenograft efficacy of three antitumor nucleoside analogs. (United States)

    Bagley, Rebecca G; Roth, Stephanie; Kurtzberg, Leslie S; Rouleau, Cecile; Yao, Min; Crawford, Jennifer; Krumbholz, Roy; Lovett, Dennis; Schmid, Steven; Teicher, Beverly A


    Nucleoside analogs are rationally designed anticancer agents that disrupt DNA and RNA synthesis. Fludarabine and cladribine have important roles in the treatment of hematologic malignancies. Clofarabine is a next generation nucleoside analog which is under clinical investigation. The bone marrow toxicity, tumor cell cytotoxicity and human tumor xenograft activity of fludarabine, cladribine and clofarabine were compared. Mouse and human bone marrow were subjected to colony forming (CFU-GM) assays over a 5-log concentration range in culture. NCI-60 cell line screening data were compared. In vivo, a range of clofarabine doses was compared with fludarabine for efficacy in several human tumor xenografts. The IC90 concentrations for fludarabine and cladribine for mouse CFU-GM were >30 and 0.93 microM, and for human CFU-GM were 8 and 0.11 microM, giving mouse to human differentials of >3.8- and 8.5-fold. Clofarabine produced IC90s of 1.7 microM in mouse and 0.51 microM in human CFU-GM, thus a 3.3-fold differential between species. In the NCI-60 cell line screen, fludarabine and cladribine showed selective cytotoxicity toward leukemia cell lines while for clofarabine there was no apparent selectivity based upon origin of the tumor cells. In vivo, clofarabine produced a dose-dependent increase in tumor growth delay in the RL lymphoma, the RPMI-8226 multiple myeloma, and HT-29 colon carcinoma models. The PC3 prostate carcinoma was equally responsive to clofarabine and fludarabine. Bringing together bone marrow toxicity data, tumor cell line cytotoxicity data, and human tumor xenograft efficacy provides valuable information for the translation of preclinical findings to the clinic.

  4. Inhibition of human breast cancer xenograft growth by cruciferous vegetable constituent benzyl isothiocyanate. (United States)

    Warin, Renaud; Xiao, Dong; Arlotti, Julie A; Bommareddy, Ajay; Singh, Shivendra V


    Benzyl isothiocyanate (BITC), a constituent of cruciferous vegetables such as garden cress, inhibits growth of human breast cancer cell lines in culture. The present study was undertaken to determine in vivo efficacy of BITC against MDA-MB-231 human breast cancer xenografts. The BITC administration retarded growth of MDA-MB-231 cells subcutaneously implanted in female nude mice without causing weight loss or any other side effects. The BITC-mediated suppression of MDA-MB-231 xenograft growth correlated with reduced cell proliferation as revealed by immunohistochemical analysis for Ki-67 expression. Analysis of the vasculature in the tumors from BITC-treated mice indicated smaller vessel area compared with control tumors based on immunohistochemistry for angiogenesis marker CD31. The BITC-mediated inhibition of angiogenesis in vivo correlated with downregulation of vascular endothelial growth factor (VEGF) receptor 2 protein levels in the tumor. Consistent with these results, BITC treatment suppressed VEGF secretion and VEGF receptor 2 protein levels in cultured MDA-MB-231 cells. Moreover, the BITC-treated MDA-MB-231 cells exhibited reduced capacity for migration compared with vehicle-treated control cells. In contrast to cellular data, BITC administration failed to elicit apoptotic response as judged by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. In conclusion, the present study demonstrates in vivo anti-cancer efficacy of BITC against MDA-MB-231 xenografts in association with reduced cell proliferation and suppression of neovascularization. These preclinical observations merit clinical investigation to determine efficacy of BITC against human breast cancers.

  5. Antiangiogenic effects of pazopanib in xenograft hepatocellular carcinoma models: evaluation by quantitative contrast-enhanced ultrasonography

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    Wu Wei-Zhong


    Full Text Available Abstract Background Antiangiogenesis is a promising therapy for advanced hepatocellular carcinoma (HCC, but the effects are difficult to be evaluated. Pazopanib (GW786034B is a pan-vascular endothelial growth factor receptor inhibitor, the antitumor effects or antiangiogenic effects haven't been investigated in HCC. Methods In vitro direct effects of pazopanib on human HCC cell lines and endothelial cells were evaluated. In vivo antitumor effects were evaluated in three xenograft nude mice models. In the subcutaneous HCCLM3 model, intratumoral blood perfusion was detected by contrast-enhanced ultrasonography (CEUS, and serial quantitative parameters were profiled from the time-intensity curves of ultrasonograms. Results In vitro proliferation of various HCC cell lines were not inhibited by pazopanib. Pazopanib inhibited migration and invasion and induced apoptosis significantly in two HCC cell lines, HCCLM3 and PLC/PRF/5. Proliferation, migration, and tubule formation of human umbilical vein endothelial cells were inhibited by pazopanib in a dose-dependent manner. In vivo tumor growth was significantly inhibited by pazopanib in HCCLM3, HepG2, and PLC/PRF/5 xenograft models. Various intratumoral perfusion parameters changed over time, and the signal intensity was significantly impaired in the treated tumors before the treatment efficacy on tumor size could be observed. Mean transit time of the contrast media in hotspot areas of the tumors was reversely correlated with intratumoral microvessel density. Conclusions Antitumor effects of pazopanib in HCC xenografts may owe to its antiangiogenic effects, and the in vivo antiangiogenic effects could be evaluated by quantitative CEUS.

  6. CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer. (United States)

    Savari, Sayeh; Liu, Minghui; Zhang, Yuan; Sime, Wondossen; Sjölander, Anita


    The expression of the inflammatory G-protein coupled receptor CysLT1R has been shown to be upregulated in colon cancer patients and associated with poor prognosis. The present study investigated the correlation between CysLT1R and colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or Montelukast) and the nude mouse xenograft model. Two drug administration regimens were established. The first regimen was established to investigate the importance of CysLT1R in tumor initiation. Nude mice were inoculated with 50 µM CysLT1R antagonist-pretreated HCT-116 colon cancer cells and received continued treatment (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT-116 cells and did not receive CysLT1R antagonist treatment until recordable tumor appearance. Both regimens resulted in significantly reduced tumor size, attributed to changes in proliferation and apoptosis as determined by reduced Ki-67 levels and increased levels of p21(WAF/Cip1) (Pcolon cancer cell line HCT-116 and CysLT1R antagonists. In addition to significant reductions in cell proliferation, adhesion and colony formation, we observed induction of cell cycle arrest and apoptosis in a dose-dependent manner. The ability of Montelukast to inhibit growth of human colon cancer xenograft was further validated by using two additional colon cancer cell lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit growth of colon cancer xenografts primarily by reducing proliferation and inducing apoptosis of the tumor cells.

  7. Teratomas produced from human pluripotent stem cells xenografted into immunodeficient mice - a histopathology atlas (United States)

    Damjanov, Ivan; Andrews, Peter W.


    This atlas illustrates the microscopic features of tumors produced from human pluripotent stem cells (hPSCs) xenografted into immunosuppressed mice, according to the generally accepted protocols for performing this teratoma assay of stem cell pluripotency. Microphotographs depict various hematoxylin and eosin (H&E) stained tissues derived from all three embryonic germ layers (ectoderm, mesoderm and endoderm). The appearance of persistent hPSC in teratomas is also described with special emphasis on the morphogenesis of embryoid bodies and yolk sac components surrounding them. The use of immunohistochemistry for analyzing hPSC-derived teratomas is also illustrated. PMID:28000905

  8. Stimulation of osteoblast activity by induction of Aloe vera and xenograft combination

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    Utari Kresnoadi


    Full Text Available Background: Tooth extraction is generally followed by alveolar ridge resorption that later can cause flat ridge. Aloe vera have biogenic stimulator and hormone activities for wound healing. Purpose: This study was aimed to know osteoblast activities in alveolar bone after induction of Aloe vera and XCB combination. Methods: Fifty four of Cavia cabaya were divided into three main groups. Group I was control group. Group II was filled with xenograft concelous bovine (XCB and group III was filled with the combination of Aloe vera gel and XCB. Then, each group was divided into three sub groups according to timing, they are 14, 30, and 60 days after tooth extraction and application. Histology and morphology examination were performed on the harvested specimens. Results: There were significant differences between the control group and the other groups filled with the combination of Aloe vera and XCB. Conclusion: In conclusion, the application of Aloe vera gel and xenograft combination decrease the number of osteoclast and increase the number of osteoblast in post tooth extraction alveolar bone structure indicating the new growth of alveolar bone.Latar belakang: Pencabutan gigi pada umumnya selalu diikuti resopsi tulang alveolar, sehingga bila terjadi dalam waktu yang lama ridge akan menjadi flat. Aloe vera adalah bahan stimulasi biogenik dan mempunyai aktivitas hormon untuk proses penyembuhan luka. Tujuan: Tujuan dari penelitian ini adalah untuk mengetahui aktivitas osteoblas pada tulang alveol dengan pemberian kombinasi Aloe vera gel dan xenograft concelous bovine (XCB. Metode: Lima puluh empat ekor Cavia cabaya, dibagi menjadi 3 kelompok besar, kelompok pertama adalah kelompok kontrol yaitu hanya dilakukan pencabutan saja tanpa perlakuan, kelompok ke-2 yaitu kelompok yang setelah dicabut diberi XCB saja dan kelompok ke-3 yaitu kelompok yang setelah pencabutan diberi kombinasi Aloe vera gel dengan XCB pada luka bekas pencabutan gigi. Kemudian masing

  9. Antitumoral effects of vasoactive intestinal peptide in human renal cell carcinoma xenografts in athymic nude mice. (United States)

    Vacas, Eva; Arenas, M Isabel; Muñoz-Moreno, Laura; Bajo, Ana M; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J


    We studied antitumor effect of VIP in human renal cell carcinoma (RCC) (A498 cells xenografted in immunosuppressed mice). VIP-treated cells gave resulted in p53 upregulation and decreased nuclear β-catenin translocation and NFκB expression, MMP-2 and MMP-9 activities, VEGF levels and CD-34 expression. VIP led to a more differentiated tubular organization in tumours and less metastatic areas. Thus, VIP inhibits growth of A498-cell tumours acting on the major issues involved in RCC progression such as cell proliferation, microenvironment remodelling, tumour invasion, angiogenesis and metastatic ability. These antitumoral effects of VIP offer new therapeutical possibilities in RCC treatment.

  10. Shift of microRNA profile upon orthotopic xenografting of glioblastoma spheroid cultures

    DEFF Research Database (Denmark)

    Halle, Bo; Thomassen, Mads; Venkatesan, Ranga;


    Glioblastomas always recur despite surgery, radiotherapy and chemotherapy. A key player in the therapeutic resistance may be immature tumor cells with stem-like properties (TSCs) escaping conventional treatment. A group of promising molecular targets are microRNAs (miRs). miRs are small non......-coding RNAs exerting post-transcriptional regulation of gene expression. In this study we aimed to identify over-expressed TSC-related miRs potentially amenable for therapeutic targeting. We used non-differentiated glioblastoma spheroid cultures (GSCs) containing TSCs and compared these to xenografts using...

  11. Migrating glioma cells express stem cell markers and give rise to new tumors upon xenografting

    DEFF Research Database (Denmark)

    Munthe, Sune; Sørensen, Mia D; Thomassen, Mads


    cells (CSCs), has been identified in gliomas and many other cancers. These tumor cells have a stem cell-like phenotype and are suggested to be responsible for tumor growth, chemo- and radio-resistance as well as recurrence. However, functional evidence for migrating glioma cells having a stem cell......, but not of the commercial cell line U87MG. An in vitro limiting dilution assay showed preserved but reduced spheroid formation capacity of migrating cells. Orthotopic xenografting in mice showed preserved but reduced tumorigenic capacity. Profiling of mRNAs revealed no significant deregulation of 16 predefined CSC...

  12. Molecular Imaging of Bcr-Abl Phosphokinase in a Xenograft Model*


    Wu, Ji Yuan; David J. Yang; Angelo, Laura S.; Kohanim, Saady; Kurzrock, Razelle


    The purpose of this study was to determine whether the Bcr-Abl tyrosine kinase can be assessed by gamma imaging using an 111Indium-labeled anti-phosphotyrosine antibody, and if the response to treatment with imatinib could be detected using this imaging technique. Anti-phosphotyrosine antibody (APT) was labeled with indium (111In) using ethylenedicysteine (EC) as a chelator. To determine if 111In-EC-APT could assess a non-receptor tyrosine kinase, xenografts of the human chronic myelogenous l...

  13. Microbiological and histopathological aspects of canine pyometra (United States)

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


    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 also consisted of the counting of microorganisms colonies forming units in samples of intrauterine content, tests of antimicrobial susceptibility of the E. coli isolates and the histological examination of the uterus. E. coli was the most prevalent microorganism isolated (76.6%) and 120 strains (79.5%) were positive for sfa, 86 (56.9%) were positive for cnf, 87 (57.6%) were positive for pap, 52 (34.4%) were positive for hly, 51 (33.8%) were positive for iuc and 5 (3.3%) were positive for afa genes. One observed more sensitivity of E. coli to norfloxacin, polimixin B, sulphazotrin, chloranfenicol and enrofloxacin. In 42% of the samples of uterine walls where microorganisms were isolated, the sizes of the areas of the inflammatory responses corresponded to 39–56%. Virulence factors were identified in 98.0% of the strains evaluated, demonstrating a high frequency of potentially pathogenic E. coli. It must be considered that dogs are animals that are living in close proximity to man for thousands of years and have an important role in the transmission of E. coli to other animals and to man. PMID:24031249

  14. Chromatography purification of canine adenoviral vectors. (United States)

    Segura, María Mercedes; Puig, Meritxell; Monfar, Mercè; Chillón, Miguel


    Canine adenovirus vectors (CAV2) are currently being evaluated for gene therapy, oncolytic virotherapy, and as vectors for recombinant vaccines. Despite the need for increasing volumes of purified CAV2 preparations for preclinical and clinical testing, their purification still relies on the use of conventional, scale-limited CsCl ultracentrifugation techniques. A complete downstream processing strategy for CAV2 vectors based on membrane filtration and chromatography is reported here. Microfiltration and ultra/diafiltration are selected for clarification and concentration of crude viral stocks containing both intracellular and extracellular CAV2 particles. A DNase digestion step is introduced between ultrafiltration and diafiltration operations. At these early stages, concentration of vector stocks with good recovery of viral particles (above 80%) and removal of a substantial amount of protein and nucleic acid contaminants is achieved. The ability of various chromatography techniques to isolate CAV2 particles was evaluated. Hydrophobic interaction chromatography using a Fractogel propyl tentacle resin was selected as a first chromatography step, because it allows removal of the bulk of contaminating proteins with high CAV2 yields (88%). An anion-exchange chromatography step using monolithic supports is further introduced to remove the remaining contaminants with good recovery of CAV2 particles (58-69%). The main CAV2 viral structural components are visualized in purified preparations by electrophoresis analyses. Purified vector stocks contained intact icosahedral viral particles, low contamination with empty viral capsids (10%), and an acceptable total-to-infectious particle ratio (below 30). The downstream processing strategy that was developed allows preparation of large volumes of high-quality CAV2 stocks.

  15. Brazilian canine hepatozoonosis Hepatozoonose canina brasileira

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    Lucia Helena O'Dwyer


    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.

  16. Molecular detection of canine parvovirus in flies (Diptera) at open and closed canine facilities in the eastern United States. (United States)

    Bagshaw, Clarence; Isdell, Allen E; Thiruvaiyaru, Dharma S; Brisbin, I Lehr; Sanchez, Susan


    More than thirty years have passed since canine parvovirus (CPV) emerged as a significant pathogen and it continues to pose a severe threat to world canine populations. Published information suggests that flies (Diptera) may play a role in spreading this virus; however, they have not been studied extensively and the degree of their involvement is not known. This investigation was directed toward evaluating the vector capacity of such flies and determining their potential role in the transmission and ecology of CPV. Molecular diagnostic methods were used in this cross-sectional study to detect the presence of CPV in flies trapped at thirty-eight canine facilities. The flies involved were identified as belonging to the house fly (Mucidae), flesh fly (Sarcophagidae) and blow/bottle fly (Calliphoridae) families. A primary surveillance location (PSL) was established at a canine facility in south-central South Carolina, USA, to identify fly-virus interaction within the canine facility environment. Flies trapped at this location were pooled monthly and assayed for CPV using polymerase chain reaction (PCR) methods. These insects were found to be positive for CPV every month from February through the end of November 2011. Fly vector behavior and seasonality were documented and potential environmental risk factors were evaluated. Statistical analyses were conducted to compare the mean numbers of each of the three fly families captured, and after determining fly CPV status (positive or negative), it was determined whether there were significant relationships between numbers of flies captured, seasonal numbers of CPV cases, temperature and rainfall. Flies were also sampled at thirty-seven additional canine facility surveillance locations (ASL) and at four non-canine animal industry locations serving as negative field controls. Canine facility risk factors were identified and evaluated. Statistical analyses were conducted on the number of CPV cases reported within the past year

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

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    Michel Erika


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

  18. Rabies, canine distemper, and canine parvovirus exposure in large carnivore communities from two Zambian ecosystems. (United States)

    Berentsen, Are R; Dunbar, Mike R; Becker, Matthew S; M'soka, Jassiel; Droge, Egil; Sakuya, Nicholas M; Matandiko, Wigganson; McRobb, Rachel; Hanlon, Cathleen A


    Disease transmission within and among wild and domestic carnivores can have significant impacts on populations, particularly for threatened and endangered species. We used serology to evaluate potential exposure to rabies virus, canine distemper virus (CDV), and canine parvovirus (CPV) for populations of African lions (Panthera leo), African wild dogs (Lycaon pictus), and spotted hyenas (Crocuta crocuta) in Zambia's South Luangwa National Park (SLNP) and Liuwa Plain National Park (LPNP) as well as community lands bordering these areas. In addition, domestic dogs in the study region were evaluated for exposure to CDV and rabies. We provide the first comprehensive disease exposure data for these species in these ecosystems. Twenty-one lions, 20 hyenas, 13 wild dogs, and 38 domestic dogs were sampled across both regions from 2009 to 2011. Laboratory results show 10.5% of domestic dogs, 5.0% of hyenas, and 7.7% of wild dogs sampled were positive for CDV exposure. All lions were negative. Exposure to CPV was 10.0% and 4.8% for hyenas and lions, respectively. All wild dogs were negative, and domestic dogs were not tested due to insufficient serum samples. All species sampled were negative for rabies virus neutralizing antibodies except lions. Forty percent of lions tested positive for rabies virus neutralizing antibodies. Because these lions appeared clinically healthy, this finding is consistent with seroconversion following exposure to rabies antigen. To our knowledge, this finding represents the first ever documentation of rabies virus neutralizing antibodies consistent with rabies exposure that did not lead to clinical disease in free-ranging African lions from this region. With ever-increasing human pressure on these ecosystems, understanding disease transmission dynamics is essential for proper management and conservation of these carnivore species.

  19. 9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine). (United States)


    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Parvovirus Vaccine, Killed Virus... REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus Vaccine, Killed Virus (Canine). Parvovirus Vaccine... established as follows: (1) Twenty-five parvovirus susceptible dogs (20 vaccinates and 5 controls) shall...

  20. Soft tissue artifact in canine kinematic gait analysis

    NARCIS (Netherlands)

    Schwencke, M.; Smolders, L.A.; Bergknut, N.; Gustas, P.; Meij, B.P.; Hazewinkel, H.A.W.


    Vet Surg. 2012 Oct;41(7):829-37. doi: 10.1111/j.1532-950X.2012.01021.x. Soft tissue artifact in canine kinematic gait analysis. Schwencke M, Smolders LA, Bergknut N, Gustås P, Meij BP, Hazewinkel HA. Source Department of Clinical Sciences of Companion Animals,, Faculty of Veterinary Medicine, Utrech

  1. Improved classification, diagnosis and prognosis of canine round cell tumours

    NARCIS (Netherlands)

    Cangul, Taci


    As the name suggests, canine round cell tumour (RCTs) are composed of cells with a round morphology. There is some discrepancy amongst authors as to which tumours belong to this category, but most designate lymphomas, melanomas, plasmacytomas, transmissible venereal tumours (TVTs), histiocytomas, an

  2. Biofilm production by clinical staphylococci strains from canine otitis (United States)

    Moreira, Camila Alencar; de Oliveira, Lis Christina; Mendes, Marina Silveira; Santiago, Thiago de Melo; Barros, Eduardo Bedê; de Carvalho, Cibele Barreto Mano


    This study determined the species of 54 staphylococci isolates from canine otitis and their ability to produce biofilm through the Congo red agar method, confirmed by scanning electron microscopy. The most frequently identified species were S. intermedius and S. simulans. Results showed that 30% of the strains were biofilm producers. PMID:24031841

  3. In vitro activity of difloxacin against canine bacterial isolates

    NARCIS (Netherlands)

    Hoven, van den J.R.; Wagenaar, J.A.; Walker, R.D.


    The in vitro activity of difloxacin against canine bacterial isolates from clinical cases was studied in the United States and The Netherlands. Minimal inhibitory concentrations (MIC), the postantibiotic effect, the effect of pH on antimicrobial activity, and the bacterial killing rate tests were de

  4. Biofilm production by clinical staphylococci strains from canine otitis. (United States)

    Moreira, Camila Alencar; de Oliveira, Lis Christina; Mendes, Marina Silveira; Santiago, Thiago de Melo; Barros, Eduardo Bedê; de Carvalho, Cibele Barreto Mano


    This study determined the species of 54 staphylococci isolates from canine otitis and their ability to produce biofilm through the Congo red agar method, confirmed by scanning electron microscopy. The most frequently identified species were S. intermedius and S. simulans. Results showed that 30% of the strains were biofilm producers.

  5. Biofilm production by clinical staphylococci strains from canine otitis


    Moreira, Camila Alencar; de Oliveira, Lis Christina; Mendes, Marina Silveira; Santiago, Thiago de Melo; Barros, Eduardo Bedê; CARVALHO Cibele Barreto Mano de


    This study determined the species of 54 staphylococci isolates from canine otitis and their ability to produce biofilm through the Congo red agar method, confirmed by scanning electron microscopy. The most frequently identified species were S. intermedius and S. simulans. Results showed that 30% of the strains were biofilm producers.

  6. Biofilm production by clinical Staphylococci strains from canine otitis

    Directory of Open Access Journals (Sweden)

    Camila Alencar Moreira


    Full Text Available This study determined the species of 54 staphylococci isolates from canine otitis and their ability to produce biofilm through the Congo red agar method, confirmed by scanning electron microscopy. The most frequently identified species were S. intermedius and S. simulans. Results showed that 30% of the strains were biofilm producers.

  7. Biofilm production by clinical Staphylococci strains from canine otitis


    Camila Alencar Moreira; Lis Christina de Oliveira; Marina Silveira Mendes; Thiago de Melo Santiago; Eduardo Bedê Barros; Cibele Barreto Mano de Carvalho


    This study determined the species of 54 staphylococci isolates from canine otitis and their ability to produce biofilm through the Congo red agar method, confirmed by scanning electron microscopy. The most frequently identified species were S. intermedius and S. simulans. Results showed that 30% of the strains were biofilm producers.

  8. Morphological characterisation of vesicular structures in the canine ejaculate

    DEFF Research Database (Denmark)

    Goericke-Pesch, Sandra Kathrin; Hauck, S; Bergmann, M;


    Membrane vesicles (MV) have been identified in seminal plasma from various species and they are thought to have a significant impact on semen quality and fertilisation. Although recently presence of MV has been also described in the canine ejaculate, detailed knowledge on their morphology is miss...

  9. Canine Gouging: A Taboo Resurfacing in Migrant Urban Population

    Directory of Open Access Journals (Sweden)

    Anila Virani Noman


    Full Text Available Cosmopolitan cities have become a pool of migrants from different parts of the world, who carry their cultural beliefs and superstitions with them around the globe. Canine gouging is a kind of infant oral mutilation (IOM which is widely practiced among rural population of Africa where the primary tooth bud of the deciduous canine is enucleated. The belief is that the life threatening illnesses in children like vomiting, diarrhoea, and fevers are caused by worms which infest on tooth buds. This case report is of a 15-year-old Somalian born boy, who presented at the dental institute with intermittent pain in his lower right permanent canine which was associated with a discharging intra oral buccal sinus. The tooth was endodontically treated and then restored with composite. General dental practitioners need to be vigilant when encountered with tooth presenting unusual morphology, unilateral missing tooth, and shift in the midline due to early loss of deciduous/permanent canines. Identification of any such dental mutilation practice will need further counselling of the individual and family members. It is the duty of every dental professional to educate and safeguard the oral and dental health of general public.

  10. Generation of functional platelets from canine induced pluripotent stem cells. (United States)

    Nishimura, Toshiya; Hatoya, Shingo; Kanegi, Ryoji; Sugiura, Kikuya; Wijewardana, Viskam; Kuwamura, Mitsuru; Tanaka, Miyuu; Yamate, Jyoji; Izawa, Takeshi; Takahashi, Masahiro; Kawate, Noritoshi; Tamada, Hiromichi; Imai, Hiroshi; Inaba, Toshio


    Thrombocytopenia (TTP) is a blood disease common to canines and human beings. Currently, there is no valid therapy for this disease except blood transfusion. In this study, we report the generation of canine induced pluripotent stem cells (ciPSCs) from canine embryonic fibroblasts, and a novel protocol for creating mature megakaryocytes (MKs) and functional platelets from ciPSCs. The ciPSCs were generated using lentiviral vectors, and differentiated into MKs and platelets on OP9 stromal cells supplemented with growth factors. Our ciPSCs presented in a tightly domed shape and showed expression of a critical pluripotency marker, REX1, and normal karyotype. Additionally, ciPSCs differentiated into cells derived from three germ layers via the formation of an embryoid body. The MKs derived from ciPSCs had hyperploidy and transformed into proplatelets. The proplatelets released platelets early on that expressed specific MK and platelet marker CD41/61. Interestingly, these platelets, when activated with adenosine diphosphate or thrombin, bind to fibrinogen. Moreover, electron microscopy showed that the platelets had the same ultrastructure as peripheral platelets. Thus, we have demonstrated for the first time the generation of ciPSCs that are capable of differentiating into MKs and release functional platelets in vitro. Our system for differentiating ciPSCs into MKs and platelets promises a critical therapy for canine TTP and appears to be extensible in principle to resolve human TTP.

  11. Morphometric analysis of canine in gender determination: Revisited in India

    Directory of Open Access Journals (Sweden)

    Geetha Paramkusam


    Interpretation and Conclusion: Use of the standard mandibular CI in gender determination is recommended for forensic procedures as it was found to have an acceptable accuracy. MD width of canine may be used in a setup when only the single tooth or a fragment of a jaw is available for analysis, with due consideration to its relatively low accuracy.

  12. Complete Genome Sequence of Canine Papillomavirus Type 16


    Luff, Jennifer; Mader, Michelle; Britton, Monica; Fass, Joseph; Rowland, Peter; Orr, Carolyn; Schlegel, Richard; Yuan, Hang


    Papillomaviruses are epitheliotropic, circular, double-stranded DNA viruses within the family Papillomaviridae that are associated with benign and malignant tumors in humans and animals. We report the complete genome sequence of canine papillomavirus type 16 identified within multiple pigmented cutaneous plaques and squamous cell carcinoma from an intact female Basenji dog.

  13. Canine distemper virus - a morbillivirus in search of new hosts?

    NARCIS (Netherlands)

    T.C. Harder (Timm); A.D.M.E. Osterhaus (Albert)


    textabstractCanine distemper morbillivirus (CDV) induces a multisystemic, often fatal disease in a wide and seemingly expanding host range among the Carnivora. Several genotypes of an otherwise monotypic virus species co-circulate in a geographically restricted pattern. Interspecies transmissions fr

  14. Canine distemper virus in Lake Baikal seals (Phoca sibirica).

    NARCIS (Netherlands)

    L.V. Mamaev; I.K.G. Visser (Ilona); S.I. Belikov; N.N. Denikina; T.C. Harder (Timm); L. Goatley; B. Rima; B. Edginton; A.D.M.E. Osterhaus (Albert); T. Barrett (Thomas)


    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

  15. Compensatory canine angulation in angle Class II and III patients

    Directory of Open Access Journals (Sweden)

    Mauro Carlos Agner Busato


    Full Text Available The aim of this study was to evaluate the occurence of compensation in mesiodistal axial inclinations of canines in skeletal malocclusions patients. The sample consisted of 25 Angle Class II, division 1 malocclusion (group 1 and 19 Angle Class III malocclusion patients (group 2. After measurement of dental angulations through a method that associates plaster model photography and AutoCad software, comparisons between the groups were performed by T-test for independent samples. Results showed that there was no statistically significant difference (p < 0.05 between groups, when maxillary canine angulations were compared. Regarding the mandibular canines, there was a statistically significant difference in dental angulation, expressed by 3.2° for group 1 and 0.15° for group 2. An upright position tendency for mandibular canines was observed in the Angle Class III sample. This configures a pattern of compensatory coronary positioning, since the angulation of these teeth makes them occupy less space in the dental arch and consequently mandibular incisors can be in a more retracted position in the sagittal plane.

  16. Canine Leishmaniosis: tools for diagnosis in veterinary practice in Colombia

    Directory of Open Access Journals (Sweden)

    Víctor Acero P


    Full Text Available The objective of this article is to perform a critical analysis and guide veterinarians in the management of canine Leishmaniosis. A systematic literature review was performed between 2005 and 2014 including scientific papers which take into account experiences and reports of: pathogenesis, diagnosis, clinical presentation, treatment, vaccination, prevention and control strategies. We discuss the different aspects of VL management and aspects that should be taken into account depending on the country, after a patient is suspected or confirmed as positive, including the possibility of euthanasia. We describe the different clinical manifestations of the disease, diagnosis, signs and treatment of canine leishmaniosis. Canine leishmaniosis is present in different parts of the country, therefore it must be considered as a possible differential diagnosis in the veterinary clinic, in patients with dermatological and systemic signs that are compatible with various diseases. In Colombia, the patients diagnosed with cutaneous leishmaniasis could be treated and have a favorable prognosis, whereas in canines with diagnosis of visceral leishmaniasis euthanasia should be considered because of the public health implications.

  17. Canine versus human epilepsy: are we up to date? (United States)

    Uriarte, A; Maestro Saiz, I


    In this paper we analyse and compare features of canine and human epilepsy and we suggest new tools for better future understanding of canine epilepsy. The prevalence of epileptic seizures in dogs ranges between 0.5% and 5.7% and between 1% and 3% in the human population. Studies on human epilepsy provide a ready-made format for classification, diagnosis and treatment in veterinary epilepsy. Human studies highlight the value of a thorough seizure classification. Nevertheless, a matter of concern in canine epilepsy is the limited information regarding seizure description and classification because of the lack of EEG-video recording. Establishment of a consensus protocol for ambulatory home video-recording in dogs who suffer from epilepsy, mainly considering indications, duration of monitoring, the sufficient essential training for an optimal interpretation of ictal semiology and the methodology of recordings is needed. The ultimate goal is that the information gathered by these videos will be analysed to describe the epileptic seizures thoroughly, recognize patterns and move towards a better understanding and therefore classification of canine epileptic seizures.

  18. 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


    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.

  19. Spinosad is a potent inhibitor of canine P-glycoprotein

    NARCIS (Netherlands)

    Schrickx, Johannes A


    Inhibition of the drug transporter P-glycoprotein (P-gp) by the oral flea preventative spinosad has been suggested as the underlying cause of the drug-drug interaction with ivermectin. In this study, an in vitro model consisting of canine cells was validated to describe the inhibitory effect of drug

  20. Clinical history and hematological findings among canines with monocytic ehrlichiosis. (United States)

    Moonarmart, Walasinee; Sungpradit, Sivapong; Rawangchue, Thanakorn; Suphaphiphat, Karuna; Suksusieng, Sineenart; Jirapattharasate, Charoonluk


    Canine monocytic ehrlichiosis is a tick borne disease caused by Ehrlichia canis, an obligate intracellular rickettsial organism belonging to the family Anaplasmataceae. Canine ehrlichiosis causes hemaotological changes among infected animals which could be used as a potential predictor for diagnosing canine monocytic ehrlichiosis (CME). Ninety-four blood samples were obtained from canines that either presented for a routine health check-up or for clinical illness. A history, physical and laboratory test were conducted on each animal. All samples were examined for E. canis using a 16S rDNA polymerase chain reaction (PCR) amplification to confirm CME infection. Thirty-six of the samples were positive for E. canis using PCR and the rest were negative. The Mann-Whitney and chi-square test were used to compare the differences between the PCR-positive and negative animals. PCR-positive animals had a higher mean body temperature than PCR-negative animals. The following were significantly lower in PCR-positive animals: white blood cell count, eosinophil count, red blood cell count, hemoglobin, hematocrit, platelet count, and the random distribution of width (RDW) of the red blood cells. We evaluated complete blood cell count findings to determine factors associated with CME using multivariable logistic regression analysis and found thrombocytopenia was significantly associated with CME (OR = 0.085; 95% CI: 0.78-0.92, p < 0.001). For every decrease in the platelet count of 10,000 there was a 15% increase in the likelihood of having CME.

  1. Experimental investigation of the penetration of ultrasound nanobubbles in a gastric cancer xenograft (United States)

    Fan, Xiaozhou; Wang, Luofu; Guo, Yanli; Tong, Haipeng; Li, Lang; Ding, Jun; Huang, Haiyun


    Nanobubbles as a type of ultrasound contrast agent have attracted much interest in recent years due to their many advantages, such as strong penetrating power and high stability. However, there is still insufficient morphological evidence concerning gas-filled nanobubbles in tumor tissue spaces and tumor angiogenesis. We used a gastric cancer xenograft as an example to study this question. Nanobubbles with a particle size of 435.2 ± 60.53 nm were prepared and compared with SonoVue® microbubbles in vitro and in vivo, and they exhibited a superior contrast imaging effect. After excluding the impact of the nanobubbles in blood vessels through saline flush, we used an ultrasound burst and frozen sectioning to investigate the distribution of nanobubbles in the gastric cancer xenografts and confirmed this by transmission electron microscopy. Preliminary results showed that the nanobubbles were able to pass through the gaps between the endothelial cells in the tumor vascular system to enter the tissue space. These findings could provide morphological evidence for extravascular ultrasound imaging of tumors and serve as a foundation for the application of nanobubbles in extravascular tumor-targeted ultrasonic diagnostics and therapy.

  2. Nanosuspension delivery of paclitaxel to xenograft mice can alter drug disposition and anti-tumor activity (United States)

    Chiang, Po-Chang; Gould, Stephen; Nannini, Michelle; Qin, Ann; Deng, Yuzhong; Arrazate, Alfonso; Kam, Kimberly R.; Ran, Yingqing; Wong, Harvey


    Paclitaxel is a common chemotherapeutic agent that is effective against various cancers. The poor aqueous solubility of paclitaxel necessitates a large percentage of Cremophor EL:ethanol (USP) in its commercial formulation which leads to hypersensitivity reactions in patients. We evaluate the use of a crystalline nanosuspension versus the USP formulation to deliver paclitaxel to tumor-bearing xenograft mice. Anti-tumor efficacy was assessed following intravenous administration of three 20 mg/kg doses of paclitaxel. Paclitaxel pharmacokinetics and tissue distribution were evaluated, and differences were observed between the two formulations. Plasma clearance and tissue to plasma ratio of mice that were dosed with the nanosuspension are approximately 33- and 11-fold higher compared to those of mice that were given the USP formulation. Despite a higher tumor to plasma ratio for the nanosuspension treatment group, absolute paclitaxel tumor exposure was higher for the USP group. Accordingly, a higher anti-tumor effect was observed in the xenograft mice that were dosed with the USP formulation (90% versus 42% tumor growth inhibition). This reduction in activity of nanoparticle formulation appeared to result from a slower than anticipated dissolution in vivo. This study illustrates a need for careful consideration of both dose and systemic solubility prior utilizing nanosuspension as a mode of intravenous delivery.

  3. Spectral CT evaluation of interstitial brachytherapy in pancreatic carcinoma xenografts: preliminary animal experience

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Shudong [Jiangsu University, Department of Radiology, The Affiliated Renmin Hospital, Zhenjiang, Jiangsu (China); Shanghai Jiao tong University, School of Medicine, Department of Radiology, Ruijin Hospital, Shanghai (China); Huang, Wei; Song, Qi; Lin, Xiaozhu; Wang, Zhongmin; Chen, Kemin [Shanghai Jiao tong University, School of Medicine, Department of Radiology, Ruijin Hospital, Shanghai (China); Chen, Yerong [Jiangsu University, Department of Radiology, The Affiliated Renmin Hospital, Zhenjiang, Jiangsu (China)


    We sought to evaluate the capability of spectral CT to detect the therapeutic response to {sup 125}I interstitial brachytherapy in a pancreatic carcinoma xenograft nude mouse model. Twenty mice bearing SWl990 human pancreatic cancer cell xenografts were randomly separated into two groups: experimental (n = 10; 1.0 mCi) and control (n = 10; 0 mCi). After a two-week treatment, spectral CT was performed. Contrast-to-noise ratio (CNR) and iodine concentration (IC) in the lesions were measured and normalized to the muscle tissue, and nIC CD31 immunohistochemistry was used to measure microvessel density (MVD). The relationships between the nIC and MVD of the tumours were analysed. The nIC of the experimental group was significantly lower than that of the control group during the multiphase examination. A significant difference in the MVD was observed between the two groups (P <0.001). The nIC values of the three-phase scans have a certain positive correlation with MVD (r = 0.57, p < 0.0001; r = 0.48, p = 0.002; r = 0.63, p = 0.0017 in the 10, 25, and 60 s phase, respectively). Spectral CT can be a useful non-invasive imaging modality in evaluating the therapeutic effect of {sup 125}I interstitial brachytherapy to a pancreatic carcinoma. (orig.)

  4. p53 Small Molecule Inhibitor Enhances Temozolomide Cytotoxic Activity against Intracranial Glioblastoma Xenografts (United States)

    Dinca, Eduard B.; Lu, Kan V.; Sarkaria, Jann N.; Pieper, Russell O.; Prados, Michael D.; Haas-Kogan, Daphne A.; VandenBerg, Scott R.; Berger, Mitchel S.; James, C. David


    In this study we investigated corresponding precursor and active forms of a p53 small molecule inhibitor for effect on temozolomide (TMZ) anti-tumor activity against glioblastoma (GBM), using both in vitro and in vivo experimental approaches. Results from in vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased when GBMs with wild-type p53 were co-treated with the active form of p53 inhibitor, and this heightened cytotoxic response was accompanied by increased PARP cleavage as well as elevated cellular phospho-H2AX. Analysis of the same series of GBMs, as intracranial xenografts in athymic mice, and administering corresponding p53 inhibitor precursor, that is converted to the active compound in vivo, yielded results consistent with the in vitro analyses: i.e., TMZ + p53 inhibitor precursor co-treatment, of three distinct wild-type p53 GBM xenografts, resulted in significant enhancement of TMZ anti-tumor effect relative to treatment with TMZ alone, as indicated by serial bioluminescence monitoring as well as survival analysis (p < 0.001 for co-treatment survival benefit in each case). Mice receiving intracranial injection with p53 null GBM showed similar survival benefit from TMZ treatment regardless of the presence or absence of p53 inhibitor precursor. In total, our results indicate that the p53 active and precursor inhibitor pair enhance TMZ cytotoxicity in vitro and in vivo, respectively, and do so in a p53-dependent manner. PMID:19074867

  5. Pathologic Correlates of Primary Central Nervous System Lymphoma Defined in an Orthotopic Xenograft Model (United States)

    Kadoch, Cigall; Dinca, Eduard B.; Voicu, Ramona; Chen, Lingjing; Nguyen, Diana; Parikh, Seema; Karrim, Juliana; Shuman, Marc A.; Lowell, Clifford A.; Treseler, Patrick A.; James, C. David; Rubenstein, James L.


    Purpose The prospect for advances in the treatment of patients with primary central nervous system lymphoma (PCNSL) is likely dependent on the systematic evaluation of its pathobiology. Animal models of PCNSL are needed to facilitate the analysis of its molecular pathogenesis and for the efficient evaluation of novel therapeutics. Experimental Design We characterized the molecular pathology of CNS lymphoma tumors generated by the intracerebral implantation of Raji B lymphoma cells in athymic mice. Lymphoma cells were modified for bioluminescence imaging to facilitate monitoring of tumor growth and response to therapy. In parallel, we identified molecular features of lymphoma xenograft histopathology that are evident in human PCNSL specimens. Results Intracerebral Raji tumors were determined to faithfully reflect the molecular pathogenesis of PCNSL, including the predominant immunophenotypic state of differentiation of lymphoma cells and their reactive microenvironment. We show the expression of interleukin-4 by Raji and other B lymphoma cell lines in vitro and by Raji tumors in vivo and provide evidence for a role of this cytokine in the M2 polarization of lymphoma macrophages both in the murine model and in diagnostic specimens of human PCNSL. Conclusion Intracerebral implantation of Raji cells results in a reproducible and invasive xenograft model, which recapitulates the histopathology and molecular features of PCNSL, and is suitable for preclinical testing of novel agents. We also show for the first time the feasibility and accuracy of tumor bioluminescence in the monitoring of a highly infiltrative brain tumor. PMID:19276270

  6. Effects of antineoplastic agents and ionizing irradiation on a human testicular cancer xenograft

    Energy Technology Data Exchange (ETDEWEB)

    Osieka, R.; Pfeiffer, R.; Glatte, P.; Schmidt, C.G.; Bamberg, M.; Scherer, E.


    Chemotherapy has afforded a high percentage of definitive cures in advanced testicular cancer. Nevertheless some patients with large tumor burden still succumb to chemorefractory disease. Therefore preclinical and clinical evaluation of new drugs and agents not primarily used against this type of disease are still mandatory. For preclinical drug screening purposes heterotransplantation of specific human tumors yields a model with high validity for tumor markers and drug response. Heterotransplantation of a human embryonal testicular cancer was used for simultaneous testing of established agents such as cisplatin, melphalan, bleomycin, vinblastine, etoposide and adriamycin and some newer derivatives such as PHM or mafosfamide. Furthermore agents such as procarbazine, dacarbazine and methyl-CCNU that cross the blood-brain-barrier displayed some interesting activity. The results hint at a unique chemosensitivity pattern of the xenograft line, with some accordance between clinical response to vinblastine and bleomycin and good response of the xenografts to bleomycin but not to vinblastine. Radiotherapy was also effective against this tumor line, but there was not much difference in response when the schedule of fractionation was changed. It is concluded that a combined modality approach might salvage patients with residual, chemorefractory disease.


    Institute of Scientific and Technical Information of China (English)


    To assess whether novel analogue of nitrosoureas, 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), has antitumor effect to 06-methylguanine-DNA methyltransferase (MGMT) positive tumors in vivo. Methods: MGMT positive human glioma cell line SF-767 xenografts in nude mice were treated with SarCNU. The antitumor efficacy of SarCNU was compared with the results of 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment with or without 06-benzylguanine (06-BG) preadministration. Results: Since the SF-767 is MGMT strongly positive, BCNU treatment alone did not result in a satisfactory anticancer effect. As expected, 06-BG by depleting MGMT activity, significantly enhanced BCNU antitumor efficacy (p<0.001). More interestingly, SarCNU treatment alone had a better antitumor effect than 06-BG plus BCNU treatment (F=51.7, p=0.00036). Conclusion: Since SarCNU enters cells via extraneuronal monoamine transporter (EMT), the enhanced antitumor activity of SarCNU in this MGMT positive human tumor xenograft model may be due to the presence of EMT in SF-767.SarCNU may be used as an alternative treatment for MGMT positive tumors, specifically for tumors expressing EMT.

  8. In vivo photoacoustic tomography of EGFR overexpressed in hepatocellular carcinoma mouse xenograft. (United States)

    Zhou, Quan; Li, Zhao; Zhou, Juan; Joshi, Bishnu P; Li, Gaoming; Duan, Xiyu; Kuick, Rork; Owens, Scott R; Wang, Thomas D


    EGFR is a promising cell surface target for in vivo imaging that is highly overexpressed in hepatocellular carcinoma (HCC), a common cancer worldwide. Peptides penetrate easily into tumors for deep imaging, and clear rapidly from the circulation to minimize background. We aim to demonstrate use of an EGFR specific peptide to detect HCC xenograft tumors in mice with photoacoustic imaging. Nude mice implanted with human HCC cells that overexpress EGFR were injected intravenously with Cy5.5-labeled EGFR and scrambled control peptides respectively. Photoacoustic images collected from 0 to 24 h. Photoacoustic signal peaked in tumors at 3 h post-injection. Images from 0 to 1.8 cm beneath the skin revealed increased target-to-background (T/B) ratio from tumors. The T/B ratio was significantly greater for the EGFR versus control peptide. Clearance of signal was observed by ∼24 h. EGFR overexpression was validated with immunofluorescence and immunohistochemistry. A peptide specific for EGFR delivered systemically can detect HCC xenograft tumors in vivo with photoacoustic imaging.

  9. DADS Suppresses Human Esophageal Xenograft Tumors through RAF/MEK/ERK and Mitochondria-Dependent Pathways

    Directory of Open Access Journals (Sweden)

    Xiaoran Yin


    Full Text Available Diallyl disulfide (DADS is a natural organosulfur compound isolated from garlic. DADS has various biological properties, including anticancer, antiangiogenic, and antioxidant effects. However, the anticancer mechanisms of DADS in human esophageal carcinoma have not been elucidated, especially in vivo. In this study, MTT assay showed that DADS significantly reduced cell viability in human esophageal carcinoma ECA109 cells, but was relatively less toxic in normal liver cells. The pro–apoptotic effect of DADS on ECA109 cells was detected by Annexin V-FITC/propidium iodide (PI staining. Flow cytometry analysis showed that DADS promoted apoptosis in a dose-dependent manner and the apoptosis rate could be decreased by caspase-3 inhibitor Ac-DEVD-CHO. Xenograft study in nude mice showed that DADS treatment inhibited the growth of ECA109 tumor in both 20 and 40 mg/kg DADS groups without obvious side effects. DADS inhibited ECA109 tumor proliferation by down-regulating proliferation cell nuclear antigen (PCNA. DADS induced apoptosis by activating a mitochondria-dependent pathway with the executor of caspase-3, increasing p53 level and Bax/Bcl-2 ratio, and downregulating the RAF/MEK/ERK pathway in ECA109 xenograft tumosr. Based on studies in cell culture and animal models, the findings here indicate that DADS is an effective and safe anti-cancer agent for esophageal carcinoma.

  10. Molecular Imaging of Hepatocellular Carcinoma Xenografts with Epidermal Growth Factor Receptor Targeted Affibody Probes

    Directory of Open Access Journals (Sweden)

    Ping Zhao


    Full Text Available Hepatocellular carcinoma (HCC is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%–20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo.

  11. Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma

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    Ruifen Dong


    Full Text Available Abstract Background Patient derived xenografts (PDX are generated by transplanting the original patient’s tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC is a deadly form of ovarian/fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient. Methods In this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged (from P0 to P4 and tumors were grafted orthotopically under the ovarian bursa or subcutaneously. Results Comparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted. Conclusion Our findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC.

  12. Metformin Treatment Does Not Inhibit Growth of Pancreatic Cancer Patient-Derived Xenografts. (United States)

    Lipner, Matthew B; Marayati, Raoud; Deng, Yangmei; Wang, Xianxi; Raftery, Laura; O'Neil, Bert H; Yeh, Jen Jen


    There is currently tremendous interest in developing anti-cancer therapeutics targeting cell signaling pathways important for both cancer cell metabolism and growth. Several epidemiological studies have shown that diabetic patients taking metformin have a decreased incidence of pancreatic cancer. This has prompted efforts to evaluate metformin, a drug with negligible toxicity, as a therapeutic modality in pancreatic cancer. Preclinical studies in cell line xenografts and one study in patient-derived xenograft (PDX) models were promising, while recently published clinical trials showed no benefit to adding metformin to combination therapy regimens for locally advanced and metastatic pancreatic cancer. PDX models in which patient tumors are directly engrafted into immunocompromised mice have been shown to be excellent preclinical models for biomarker discovery and therapeutic development. We evaluated the response of four PDX tumor lines to metformin treatment and found that all four of our PDX lines were resistant to metformin. We found that the mechanisms of resistance may occur through lack of sustained activation of adenosine monophosphate-activated protein kinase (AMPK) or downstream reactivation of the mammalian target of rapamycin (mTOR). Moreover, combined treatment with metformin and mTOR inhibitors failed to improve responses in cell lines, which further indicates that metformin alone or in combination with mTOR inhibitors will be ineffective in patients, and that resistance to metformin may occur through multiple pathways. Further studies are required to better understand these mechanisms of resistance and inform potential combination therapies with metformin and existing or novel therapeutics.

  13. Load System of Segmental T-Loops for Canine Retraction (United States)

    Xia, Zeyang; Chen, Jie; Jiang, Feifei; Li, Shuning; Viecilli, Rodrigo F; Liu, Sean Y.


    Objectives The orthodontic load system, especially the ideal moment-to-force ratios (M/F), is the commonly used design parameter of segmental T-loops for canine retraction. However, the load system, including M/F, may be affected by the changes in canine angulations and interbracket distance (IBD). Here, we hypothesize that clinical changes in canine position and angulation during canine retraction will significantly affect the load system delivered to the tooth. Methods The load systems of two T-loop groups, one for translation (TR) and the other for controlled tipping (CT), from nine bilateral canine retraction patients were made to the targeted values obtained from finite element analyses and validated. Each loop was tested on the corresponding maxillary dental cast obtained in the clinic. The casts were made before and after each treatment interval so that both initial and residual load systems could be obtained. The pre- and post-treatment IBDs were recorded for calculating IBD changes. Results As the IBDs decreased, the averaged retraction-force-drop per IBD reduction was 36 cN/mm, a 30% drop per 1 mm IBD decrease. The averaged anti-tipping-moment-drops per IBD reductions were 0.02 N-mm/mm for CT and 1.4 N-mm/mm for TR, ~0.6 % and 17% drop per 1 mm IBD decrease, respectively. Consequently, the average M/F increases per 1 mm IBD reduction were 1.24 mm/mm for CT and 6.34 mm/mm for TR. There was significant residual load left, which could continue to move the tooth if the patient missed the scheduled appointment. Conclusions Clinical changes in canine position and angulation during canine retraction significantly affect the load system. The initial planned M/F needs to be lower to reach the expected average ideal value. Patients should be required to follow the office visit schedule closely to avoid negative effects due to significant M/F increases with time. PMID:24075663

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

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    Helen L. Del Puerto


    Full Text Available 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 nucleocapsid protein coding region fragment amplification (84 bp. Canine b-actin (93 bp was utilized as the endogenous control for normalization. Quantitative results of real time PCR generated by ABI Prism 7000 SDS Software showed that 54.5% of dogs with asymptomatic canine distemper were positive for canine distemper virus. Dissociation curves confirmed the specificity of the real time PCR fragments. This technique could detect even a few copies of viral RNA and identificate subclinically infected dogs providing accurate diagnosis of this disease at an early stage.A reação em cadeia da polimerase (PCR em tempo real revelou a presença do vírus da cinomose canina em amostra de sangue de cães assintomáticos e não vacinados. Amostra de onze cães domésticos sem nenhum sinal clínico de cinomose e que não foram vacinados no mês da coleta de sangue foram utilizados para análise. Amostra vacinal do vírus da cinomose canina em células VERO foi utilizada como controle positivo. O RNA total foi isolado utilizando-se Trizol®, e tratadas com o Kit TURBO DNA-free. Os iniciadores foram desenhados para amplificar a região do nucleocapsídeo viral com 319pb e 84pb para a PCR convencional e PCR em tempo real, respectivamente. O fragmento alvo da b-actina canina com 93pb foi utilizado como controle endógeno e normalizador. Resultados quantitativos da PCR em tempo real gerados pelo programa ABI Prism 7000 SDS demonstraram que 54,5% dos cães assintom

  15. Effects of body weight on antibody titers against canine parvovirus type 2, canine distemper virus, and canine adenovirus type 1 in vaccinated domestic adult dogs. (United States)

    Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Saito, Miyoko; Lynch, Jonathan; Sahara, Hiroeki


    The objective of this study was to determine whether post-vaccination antibody titers vary according to body weight in adult dogs. Antibody titers against canine parvovirus type 2 (CPV-2), canine distemper virus (CDV), and canine adenovirus type 1 (CAdV-1) were measured for 978 domestic adult dogs from 2 to 6 y of age. The dogs had been vaccinated approximately 12 mo earlier with a commercial combination vaccine. The dogs were divided into groups according to their weight. It was found that mean antibody titers in all weight groups were sufficient to prevent infection. Intergroup comparison, however, revealed that CPV-2 antibody titers were significantly higher in the Super Light ( 20 kg) groups and were also significantly higher in the Light (5 to 9.9 kg) group than in the Heavy group. Antibody titers against CDV were significantly higher in the Super Light, Light, and Medium groups than in the Heavy group. There were no significant differences among the groups for the CAdV-1 antibody titers.

  16. Determining epithelial contribution to in vivo mesenchymal tumour expression signature using species-specific microarray profiling analysis of xenografts. (United States)

    Purdom, E; Restall, C; Busuttil, R A; Schluter, H; Boussioutas, A; Thompson, E W; Anderson, R L; Speed, T P; Haviv, I


    Gene expression profiling using microarrays and xenograft transplants of human cancer cell lines are both popular tools to investigate human cancer. However, the undefined degree of cross hybridization between the mouse and human genomes hinders the use of microarrays to characterize gene expression of both the host and the cancer cell within the xenograft. Since an increasingly recognized aspect of cancer is the host response (or cancer-stroma interaction), we describe here a bioinformatic manipulation of the Affymetrix profiling that allows interrogation of the gene expression of both the mouse host and the human tumour. Evidence of microenvironmental regulation of epithelial mesenchymal transition of the tumour component in vivo is resolved against a background of mesenchymal gene expression. This tool could allow deeper insight to the mechanism of action of anti-cancer drugs, as typically novel drug efficacy is being tested in xenograft systems.

  17. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

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    Kinga Majchrzak

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

  18. Current state of knowledge: the canine gastrointestinal microbiome. (United States)

    Hooda, Seema; Minamoto, Yasushi; Suchodolski, Jan S; Swanson, Kelly S


    Gastrointestinal (GI) microbes have important roles in the nutritional, immunological, and physiologic processes of the host. Traditional cultivation techniques have revealed bacterial density ranges from 10(4) to 10(5) colony forming units (CFU)/g in the stomach, from 10(5) to 10(7) CFU/g in the small intestine, and from 10(9) to 10(11) CFU/g in the colon of healthy dogs. As a small number of bacterial species can be grown and studied in culture, however, progress was limited until the recent emergence of DNA-based techniques. In recent years, DNA sequencing technology and bioinformatics have allowed for better phylogenetic and functional/metabolic characterization of the canine gut microbiome. Predominant phyla include Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria, and Actinobacteria. Studies using 16S ribosomal RNA (rRNA) gene pyrosequencing have demonstrated spatial differences along the GI tract and among microbes adhered to the GI mucosa compared to those in intestinal contents or feces. Similar to humans, GI microbiome dysbiosis is common in canine GI diseases such as chronic diarrhea and inflammatory bowel diseases. DNA-based assays have also identified key pathogens contributing to such conditions, including various Clostridium, Campylobacter, Salmonella, and Escherichia spp. Moreover, nutritionists have applied DNA-based techniques to study the effects of dietary interventions such as dietary fiber, prebiotics, and probiotics on the canine GI microbiome and associated health indices. Despite recent advances in the field, the canine GI microbiome is far from being fully characterized and a deeper characterization of the phylogenetic and functional/metabolic capacity of the GI microbiome in health and disease is needed. This paper provides an overview of recent studies performed to characterize the canine GI microbiome.

  19. MicroRNA expression in canine mammary cancer. (United States)

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


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

  20. Survey of canine babesiosis in South Africa

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    M.G. Collett


    Full Text Available A questionnaire, designed to obtain qualitative information on a number of variables concerning canine babesiosis (biliary fever in South Africa, was sent to 510 veterinary practices in late 1993. Of the 157 practices that responded, all were presented with cases of babesiosis and most were situated in Gauteng, the Western Cape and KwaZulu-Natal. Apart from the Western Cape, a winter-rainfall region, the prevalence of babesiosis cases in dogs was highest in summer. Most of the respondent practices treated between 1000 and 5000 sick dogs that included 100 to 500 babesiosis cases each year. Respondents identified cerebral babesiosis, enterorrhagia, 'red' or haemoconcentrated babesiosis, acute renal failure and pulmonary babesiosis or 'shock lung', amongst others, as the most prevalent forms of complicated ('atypical' babesiosis. Diminazene, imidocarb and trypan blue were the most popular antibabesials. Trypan blue was most often used in shocked patients, whereas diminazene and imidocarb were preferred when there was a high parasitaemia in the absence of shock. At least 19 antibabesial treatment regimens were used in practices. These comprised the use of single doses of antibabesial drugs; split doses with repeat injections, and combined drug variations, some of which are undesirable due to possible sterilisation of Babesia infection or potential toxicity. Side-effects were most commonly associated with imidocarb use. Ninety-six percent of respondents used supportive treatment (e.g. corticosteroids, vitamins and 'liver support' in all cases of babesiosis. The use of blood transfusion as supportive treatment varied according to practice and severity of the case. Most practices never cross-matched blood to be transfused, and transfusion reactions were rare. Diminazene was most frequently incriminated in cases where drug 'resistance' or relapses occurred. Cerebral and 'red' cases resulted in high mortality. Treatment of babesiosis costs the dog

  1. Release of canine parvovirus from endocytic vesicles. (United States)

    Suikkanen, Sanna; Antila, Mia; Jaatinen, Anne; Vihinen-Ranta, Maija; Vuento, Matti


    Canine parvovirus (CPV) is a small nonenveloped virus with a single-stranded DNA genome. CPV enters cells by clathrin-mediated endocytosis and requires an acidic endosomal step for productive infection. Virion contains a potential nuclear localization signal as well as a phospholipase A(2) like domain in N-terminus of VP1. In this study we characterized the role of PLA(2) activity on CPV entry process. PLA(2) activity of CPV capsids was triggered in vitro by heat or acidic pH. PLA(2) inhibitors inhibited the viral proliferation suggesting that PLA(2) activity is needed for productive infection. The N-terminus of VP1 was exposed during the entry, suggesting that PLA(2) activity might have a role during endocytic entry. The presence of drugs modifying endocytosis (amiloride, bafilomycin A(1), brefeldin A, and monensin) caused viral proteins to remain in endosomal/lysosomal vesicles, even though the drugs were not able to inhibit the exposure of VP1 N-terminal end. These results indicate that the exposure of N-terminus of VP1 alone is not sufficient to allow CPV to proliferate. Some other pH-dependent changes are needed for productive infection. In addition to blocking endocytic entry, amiloride was able to block some postendocytic steps. The ability of CPV to permeabilize endosomal membranes was demonstrated by feeding cells with differently sized rhodamine-conjugated dextrans together with the CPV in the presence or in the absence of amiloride, bafilomycin A(1), brefeldin A, or monensin. Dextran with a molecular weight of 3000 was released from vesicles after 8 h of infection, while dextran with a molecular weight of 10,000 was mainly retained in vesicles. The results suggest that CPV infection does not cause disruption of endosomal vesicles. However, the permeability of endosomal membranes apparently changes during CPV infection, probably due to the PLA(2) activity of the virus. These results suggest that parvoviral PLA(2) activity is essential for productive

  2. Cardiac troponin I levels in canine pyometra (United States)

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


    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 parameters were associated with cTnI increase. Methods Preoperative plasma levels of cTnI were investigated in 58 female dogs with pyometra and 9 controls. The value of physical examination findings, haematological, serum biochemical and pro-inflammatory (CRP and TNF-α) parameters as possible predictors of increased cTnI levels was also evaluated. Results Seven dogs with pyometra (12%) and one control dog (11%) had increased levels of cTnI. In the pyometra group, the levels ranged between 0.3–0.9 μg l-1 and in the control dog the level was 0.3 μg l-1. The cTnI levels did not differ significantly between the two groups. No cardiac abnormalities were evident on preoperative physical examinations. Four of the pyometra patients died within two weeks of surgery, of which two were examined post mortem. In one of these cases (later diagnosed with myocarditis and disseminated bacterial infection) the cTnI levels increased from 0.9 μg l-1 preoperatively to 180 μg l-1 the following day when also heart arrhythmia was also detected. The other patient had cTnI levels of 0.7 μg l-1 with no detectable heart pathology post mortem. CTnI increase was not associated with presence of SIRS. There was a trend for the association of cTnI increase with increased mortality. No preoperative physical examination findings and few but unspecific laboratory parameters were associated with increased cTnI levels. Conclusion Increased cTnI levels were observed in 12% of the dogs with pyometra. The proportions of dogs

  3. Cardiac troponin I levels in canine pyometra

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    Hagman Ragnvi


    Full Text Available 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 parameters were associated with cTnI increase. Methods Preoperative plasma levels of cTnI were investigated in 58 female dogs with pyometra and 9 controls. The value of physical examination findings, haematological, serum biochemical and pro-inflammatory (CRP and TNF-α parameters as possible predictors of increased cTnI levels was also evaluated. Results Seven dogs with pyometra (12% and one control dog (11% had increased levels of cTnI. In the pyometra group, the levels ranged between 0.3–0.9 μg l-1 and in the control dog the level was 0.3 μg l-1. The cTnI levels did not differ significantly between the two groups. No cardiac abnormalities were evident on preoperative physical examinations. Four of the pyometra patients died within two weeks of surgery, of which two were examined post mortem. In one of these cases (later diagnosed with myocarditis and disseminated bacterial infection the cTnI levels increased from 0.9 μg l-1 preoperatively to 180 μg l-1 the following day when also heart arrhythmia was also detected. The other patient had cTnI levels of 0.7 μg l-1 with no detectable heart pathology post mortem. CTnI increase was not associated with presence of SIRS. There was a trend for the association of cTnI increase with increased mortality. No preoperative physical examination findings and few but unspecific laboratory parameters were associated with increased cTnI levels. Conclusion Increased cTnI levels were observed in 12% of the dogs with pyometra. The

  4. Enterohemorrhagic Escherichia coli induce attaching and effacing lesions and hemorrhagic colitis in human and bovine intestinal xenograft models

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    Lilach Golan


    Enterohemorrhagic Escherichia coli (EHEC O157:H7 is an important cause of diarrhea, hemorrhagic colitis and hemolytic uremic syndrome in humans worldwide. The two major virulence determinants of EHEC are the Shiga toxins (Stx and the type III secretion system (T3SS, including the injected effectors. Lack of a good model system hinders the study of EHEC virulence. Here, we investigated whether bovine and human intestinal xenografts in SCID mice can be useful for studying EHEC and host tissue interactions. Fully developed, germ-free human and bovine small intestine and colon were established by subcutaneous transplantation of human and bovine fetal gut into SCID mice. Xenografts were allowed to develop for 3–4 months and thereafter were infected by direct intraluminal inoculation of Stx-negative derivatives of EHEC O157:H7, strain EDL933. The small intestine and colon xenografts closely mimicked the respective native tissues. Upon infection, EHEC induced formation of typical attaching and effacing lesions and tissue damage that resembled hemorrhagic colitis in colon xenografts. By contrast, xenografts infected with an EHEC mutant deficient in T3SS remained undamaged. Furthermore, EHEC did not attach to or damage the epithelium of small intestinal tissue, and these xenografts remained intact. EHEC damaged the colon in a T3SS-dependent manner, and this model is therefore useful for studying the molecular details of EHEC interactions with live human and bovine intestinal tissue. Furthermore, we demonstrate that Stx and gut microflora are not essential for EHEC virulence in the human gut.

  5. Site-specific rectocele repair with dermal graft augmentation: comparison of porcine dermal xenograft (Pelvicol) and human dermal allograft. (United States)

    Biehl, Roger C; Moore, Robert D; Miklos, John R; Kohli, Neeraj; Anand, Indu S; Mattox, T Fleming


    This study is a retrospective chart review comparing 195 women who underwent rectocele repair with either a porcine dermal xenograft or human allogenic cadaveric dermal graft augmentation over a two year period. A site-specific defect repair was completed prior to augmentation with the graft. Examinations were performed preoperatively and postoperatively using the pelvic organ prolapse quantification system. Questionnaires were used to assess constipation and dyspareunia. De novo dyspareunia and cure rates for constipation and dyspareunia were not statistically different between the two groups. Site-specific fascial rectocele repairs with xenograft or allograft augmentation were found to have similar complication rates as well as objective and subjective cure rates.

  6. The TCD[sub 50] and regrowth delay assay in human tumor xenografts: Differences and implications

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    Budach, W.; Budach, V.; Stuschke, M.; Dinges, S.; Sack, H. (Univ. of Essen (Germany))


    The response to irradiation of five human xenograft cell lines - a malignant paraganglioma, a neurogenic sarcoma, a malignant histiocytoma, a primary lymphoma of the brain, and a squamous cell carcinoma - were tested in nude mice. All mice underwent 5 Gy whole body irradiation prior to xenotransplantation to minimize the residual immune response. The subcutaneous tumors were irradiated at a tumor volume of 120 mm[sup 3] under acutely hypoxic conditions with single doses between 8 Gy and 80 Gy depending on the expected radiation sensitivity of the tumor line. Endpoints of the study were the tumor control dose 50% (TCD[sub 50]) and the regrowth delay endpoints growth delay, specific growth delay, and the tumor bed effect corrected specific growth delay. Specific growth delay and corrected specific growth delay at 76% of the TCD[sub 50] was used in order to compare the data to previously published data from spheroids. The lowest TCD[sub 50] was found in the lymphoma with 24.9 Gy, whereas the TCD[sub 50] of the soft tissue sarcomas and the squamous cell carcinoma ranged from 57.8 Gy to 65.6 Gy. The isoeffective dose levels for the induction of 30 days growth delay, a specific growth delay of 3, and a corrected specific growth delay of 3 ranged from 15.5 Gy (ECL1) to 37.1 Gy (FADU), from 7.2 Gy (ENE2) to 45.6 Gy (EPG1) and from 9.2 Gy (ENE2) to 37.6 Gy (EPG1), respectively. The corrected specific growth delay at 76% of the TCD[sub 50] was correlated with the number of tumor rescue units per 100 cells in spheroids, which was available for three tumor lines, and with the tumor doubling time in xenografts (n = 5). The TCD[sub 50] values corresponded better to the clinical experience than the regrowth delay data. There was no correlation between TCD[sub 50] and any of the regrowth delay endpoints. This missing correlation was most likely a result of large differences in the number of tumor rescue units in human xenografts of the same size.

  7. Differentiation-inducing and anti-proliferative activities of lupeol on canine melanoma cells. (United States)

    Ogihara, Kikumi; Naya, Yuko; Okamoto, Yoshiharu; Hata, Keishi


    Canine melanoma is the most common oral malignant tumor reported in the field of veterinary medicine. We found that lupeol, a lupine triterpene, inhibited mouse melanoma cell growth in vitro and in vivo by inducing cell differentiation. In the present study, we examined the differentiation-inducing activities of lupeol on 4 canine melanoma cells in vitro and in vivo. The induction of canine melanoma cell differentiation by lupeol was confirmed by evaluating some differentiation markers such as tyrosinase with real-time RT-PCR. Furthermore, we transplanted canine melanoma cells into a severe combined immunodeficiency mouse, and studied the anti-progressive effects of lupeol on tumor tissue. The gene expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related protein-2, which are markers of pigment cell differentiation, was induced in 4 canine oral malignant melanoma cells by lupeol, and the agent markedly inhibited tumor progression in canine melanoma-bearing mice.

  8. Orthodontic management of buccally erupted ectopic canine with two case reports

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    Avesh Sachan


    Full Text Available Ectopic canine teeth develop displaced from their normal position. Any permanent tooth can be ectopic, and the cause may be both genetic and environmental. Orthodontic treatment is justified because ectopic canine teeth can migrate in the jaw bone and may damage the adjacent teeth roots and bone. Orthodontic treatment is also justifiable for aesthetic reasons. Diagnosis and treatment of ectopically erupting permanent maxillary canines requires timely management by the orthodontist. Internal or external root resorption of teeth adjacent to the ectopic canine is the most common sequel. Malocclusion with severe crowding is difficult to treat without extraction. Non-extraction treatment of ectopic canines can compromise the patient′s profile. This article represents two cases of extraction treatment approach for buccally displaced or ectopic canine in a patient with severe crowding in the mandibular arch.

  9. Orthodontic management of buccally erupted ectopic canine with two case reports. (United States)

    Sachan, Avesh; Chaturvedi, T P


    Ectopic canine teeth develop displaced from their normal position. Any permanent tooth can be ectopic, and the cause may be both genetic and environmental. Orthodontic treatment is justified because ectopic canine teeth can migrate in the jaw bone and may damage the adjacent teeth roots and bone. Orthodontic treatment is also justifiable for aesthetic reasons. Diagnosis and treatment of ectopically erupting permanent maxillary canines requires timely management by the orthodontist. Internal or external root resorption of teeth adjacent to the ectopic canine is the most common sequel. Malocclusion with severe crowding is difficult to treat without extraction. Non-extraction treatment of ectopic canines can compromise the patient's profile. This article represents two cases of extraction treatment approach for buccally displaced or ectopic canine in a patient with severe crowding in the mandibular arch.

  10. Canine hypothyroidism. A diagnostic challenge?; Die canine Hypothyreose. Eine diagnostische Herausforderung?

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    Boretti, Felicitos; Reusch, C.E. [Klinik fuer Kleintiermedizin, Vetsuisse Fakultaet Zuerich, Univ. Zuerich (Switzerland)


    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 {sup 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

  11. [Effects of compound Zhe-Bei granule (CZBG) combined with doxorubicin on expression of membrane transport proteins in K562/A02 cell xenografts]. (United States)

    Li, Dong-Yun; Zheng, Zhi; Hou, Li; Jiang, Miao; Dong, Qing; Tian, Shao-Dan; Ma, Wei; Chen, Ju; Wang, Jing; Chen, Xin-Yi


    This study was purposed to investigate the effects of compound Zhe-Bei granule (CZBG) combined with doxorubicin on expressions of P-gp, MRP, LRP in K562/A02 cell xenografts. Tumor xenograft model were established by injecting the multidrug resistant cell line K562/A02 in the axillary flank of BALB/c-nu-nu mice. CZBG-intragastric administration and doxorubicin-intraperitoneal injection in combination were given to the BALB/c-nu nude mice. The tumor xenografts were made into slice after the dissection, and the expression of P-gp, MRP, LRP in K562/A02 tumor xenografts in mice were investigated by immunohistochemical technique. The integral optical density (IOD) of P-gp, MRP, LRP in K562/A02 tumor xenografts were measured by Image Pro Plus 6.0. The results showed that as compared with the doxorubicin alone, the combination of the doxorubicin and CZBG with high, middle and low dosage could decrease IOD of P-gp, MRP in K562/A02 tumor xenografts with statistical significance (p < 0.05). The LRP expression in K562/A02 tumor xenografts was not observed in five groups. It is concluded that the combination of CZBG with doxorubicin decreases the expressions of P-gp, MRP in K562/A02 tumor xenografts of mice.


    NARCIS (Netherlands)



    In the WAG/Rij nude rat, subcutaneous (s.c.) and intracerebral (i.c.) xenografts of the human SCLC cell line GLC-28 were evaluated for their growth behavior, in vivo monoclonal antibody binding and presence of tumor infiltrating lymphocytes. For the i.c. xenografts, two models of cerebral tumor grow

  13. Impacted maxillary canines and root resorption of adjacent teeth: A retrospective observational study (United States)

    Cavallini, Costanza; Vernucci, Roberto; Vichi, Maurizio; Leonardi, Rosalia; Barbato, Ersilia


    Background The prevalence of impacted maxillary canine is reported to be between 1% and 3%. The lack of monitoring and the delay in the treatment of the impacted canine can cause different complications such as: displacement of adjacent teeth, loss of vitality of neighbouring teeth, shortening of the dental arch, follicular cysts, canine ankylosis, recurrent infections, recurrent pain, internal resorption of the canine and the adjacent teeth, external resorption of the canine and the adjacent teeth, combination of these factors. An appropriate diagnosis, accurate predictive analysis and early intervention are likely to prevent such undesirable effects. The objective is to evaluate, by means of a retrospective observational study, the possibility of carrying out a predictive analysis of root resorption adjacent to the impacted canines by means of orthopantomographs, so as to limit the prescription of additional 3D radiography. Material and Methods 120 subjects with unilateral or bilateral maxillary impacted canine were examined and 50 patients with 69 impacted maxillary canine (22 male, 28 female; mean age: 11.7 years) satisfied the inclusion criteria of the study. These patients were subjected to a basic clinical and radiographic investigation (orthopantomographs and computerized tomography). All panoramic films were viewed under standardized conditions for the evaluation of two main variables: maxillary canine angulations (a, b, g angles) and the overlapping between the impacted teeth and the lateral incisor (Analysis of Lindauer). Binary logistic regression was used to estimate the likelihood of resorbed lateral incisors depending on sector location and angle measurements. Results Results indicated that b angle has the greatest influence on the prediction of root resorption (predictive value of b angle = 76%). If β angle resorption is 0.06. Conclusions Evaluation of b angle and superimposition lateral incisor/impacted canine analysed on orthopantomographs could

  14. 3 '2' 1: Orthodontic re-positioning of canines into central incisors. (United States)

    Mahdmina, A; Malik, O; Ashley, M; Waring, D


    Resorption of lateral incisors caused by impacted maxillary canines is frequently reported. However, resorption of the central incisor is less common and management of such a finding can prove to be a challenge for the clinician. This article reviews the literature of impacted canines and incisor resorption. The management of two cases of severe central incisor resorption caused by an impacted maxillary canine is also described.

  15. Orthodontic management of buccally erupted ectopic canine with two case reports


    Avesh Sachan; T P Chaturvedi


    Ectopic canine teeth develop displaced from their normal position. Any permanent tooth can be ectopic, and the cause may be both genetic and environmental. Orthodontic treatment is justified because ectopic canine teeth can migrate in the jaw bone and may damage the adjacent teeth roots and bone. Orthodontic treatment is also justifiable for aesthetic reasons. Diagnosis and treatment of ectopically erupting permanent maxillary canines requires timely management by the orthodontist. Internal o...

  16. Medical dissolution and prevention of canine and feline uroliths: diagnostic and therapeutic caveats. (United States)

    Osborne, C A; Lulich, J P; Bartges, J W; Felice, L J


    Medical protocols designed to promote the dissolution of canine and feline struvite uroliths, the dissolution of canine ammonium urate and cystine uroliths and the prevention of all major types of canine and feline uroliths have been developed. However, because the causes of different types of uroliths vary, the medical protocols for their dissolution and prevention also vary. When the diagnosis of the underlying causes of uroliths becomes the rule rather than the exception, therapeutic failures should become the exception rather than the rule.

  17. Comparison of canine parvovirus with mink enteritis virus by restriction site mapping.


    McMaster, G K; Tratschin, J D; Siegl, G


    The genomes of canine parvovirus and mink enteritis virus were compared by restriction enzyme analysis of their replicative-form DNAs. Of 79 mapped sites, 68, or 86%, were found to be common for both types of DNA, indicating that canine parvovirus and mink enteritis virus are closely related viruses. Whether they evolved from a common precursor or whether canine parvovirus is derived from mink enteritis virus, however, cannot be deduced from our present data.

  18. Patient-derived xenografts as models for personalized medicine research in cancer

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    Marco Perez


    Full Text Available Basic research and clinical trials are essential components of the process of discovery and development of new drugs. The use of preclinical models is a key component in every aspect of drug development in cancer. Unfortunately, preclinical models often fail to capture the diverse heterogeneity of human malignancies, and the correlation between the antitumor activity of cytotoxic agents observed in these animal models and that observed in humans is poor. In recent years, there has been an increasing interest in the application of preclinical cancer models which can actually recapitulate the clinical disease, including patient-derived xenografts (PDXs. PDX models maintain the phenotypic, genetic, and molecular characteristics of the original tumor and reflect tumor pathology. This review discusses the limitation of the conventional strategy of developing new drugs in oncology and proposes the PDX models as a powerful technology for the biological study of tumors and to evaluate the antitumoral effect of new compounds.

  19. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response. (United States)

    Gao, Hui; Korn, Joshua M; Ferretti, Stéphane; Monahan, John E; Wang, Youzhen; Singh, Mallika; Zhang, Chao; Schnell, Christian; Yang, Guizhi; Zhang, Yun; Balbin, O Alejandro; Barbe, Stéphanie; Cai, Hongbo; Casey, Fergal; Chatterjee, Susmita; Chiang, Derek Y; Chuai, Shannon; Cogan, Shawn M; Collins, Scott D; Dammassa, Ernesta; Ebel, Nicolas; Embry, Millicent; Green, John; Kauffmann, Audrey; Kowal, Colleen; Leary, Rebecca J; Lehar, Joseph; Liang, Ying; Loo, Alice; Lorenzana, Edward; Robert McDonald, E; McLaughlin, Margaret E; Merkin, Jason; Meyer, Ronald; Naylor, Tara L; Patawaran, Montesa; Reddy, Anupama; Röelli, Claudia; Ruddy, David A; Salangsang, Fernando; Santacroce, Francesca; Singh, Angad P; Tang, Yan; Tinetto, Walter; Tobler, Sonja; Velazquez, Roberto; Venkatesan, Kavitha; Von Arx, Fabian; Wang, Hui Qin; Wang, Zongyao; Wiesmann, Marion; Wyss, Daniel; Xu, Fiona; Bitter, Hans; Atadja, Peter; Lees, Emma; Hofmann, Francesco; Li, En; Keen, Nicholas; Cozens, Robert; Jensen, Michael Rugaard; Pryer, Nancy K; Williams, Juliet A; Sellers, William R


    Profiling candidate therapeutics with limited cancer models during preclinical development hinders predictions of clinical efficacy and identifying factors that underlie heterogeneous patient responses for patient-selection strategies. We established ∼1,000 patient-derived tumor xenograft models (PDXs) with a diverse set of driver mutations. With these PDXs, we performed in vivo compound screens using a 1 × 1 × 1 experimental design (PDX clinical trial or PCT) to assess the population responses to 62 treatments across six indications. We demonstrate both the reproducibility and the clinical translatability of this approach by identifying associations between a genotype and drug response, and established mechanisms of resistance. In addition, our results suggest that PCTs may represent a more accurate approach than cell line models for assessing the clinical potential of some therapeutic modalities. We therefore propose that this experimental paradigm could potentially improve preclinical evaluation of treatment modalities and enhance our ability to predict clinical trial responses.

  20. Optimal Design for Informative Protocols in Xenograft Tumor Growth Inhibition Experiments in Mice. (United States)

    Lestini, Giulia; Mentré, France; Magni, Paolo


    Tumor growth inhibition (TGI) models are increasingly used during preclinical drug development in oncology for the in vivo evaluation of antitumor effect. Tumor sizes are measured in xenografted mice, often only during and shortly after treatment, thus preventing correct identification of some TGI model parameters. Our aims were (i) to evaluate the importance of including measurements during tumor regrowth and (ii) to investigate the proportions of mice included in each arm. For these purposes, optimal design theory based on the Fisher information matrix implemented in PFIM4.0 was applied. Published xenograft experiments, involving different drugs, schedules, and cell lines, were used to help optimize experimental settings and parameters using the Simeoni TGI model. For each experiment, a two-arm design, i.e., control versus treatment, was optimized with or without the constraint of not sampling during tumor regrowth, i.e., "short" and "long" studies, respectively. In long studies, measurements could be taken up to 6 g of tumor weight, whereas in short studies the experiment was stopped 3 days after the end of treatment. Predicted relative standard errors were smaller in long studies than in corresponding short studies. Some optimal measurement times were located in the regrowth phase, highlighting the importance of continuing the experiment after the end of treatment. In the four-arm designs, the results showed that the proportions of control and treated mice can differ. To conclude, making measurements during tumor regrowth should become a general rule for informative preclinical studies in oncology, especially when a delayed drug effect is suspected.

  1. Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer.

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    Harold D Love

    Full Text Available Benign prostatic hyperplasia (BPH and prostate carcinoma (CaP are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and CaP and which could serve as potential clinical biomarkers. In this study, we used a human prostate xenograft model to define a profile of genes regulated in vivo by androgens, with an emphasis on identifying candidate biomarkers. Benign transition zone (TZ human prostate tissue from radical prostatectomies was grafted to the sub-renal capsule site of intact or castrated male immunodeficient mice, followed by the removal or addition of androgens, respectively. Microarray analysis of RNA from these tissues was used to identify genes that were; 1 highly expressed in prostate, 2 had significant expression changes in response to androgens, and, 3 encode extracellular proteins. A total of 95 genes meeting these criteria were selected for analysis and validation of expression in patient prostate tissues using quantitative real-time PCR. Expression levels of these genes were measured in pooled RNAs from human prostate tissues with varying severity of BPH pathologic changes and CaP of varying Gleason score. A number of androgen regulated genes were identified. Additionally, a subset of these genes were over-expressed in RNA from clinical BPH tissues, and the levels of many were found to correlate with disease status. Our results demonstrate the feasibility, and some of the problems, of using a mouse xenograft model to characterize the androgen regulated expression profiles of intact human prostate tissues.

  2. Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer. (United States)

    Love, Harold D; Booton, S Erin; Boone, Braden E; Breyer, Joan P; Koyama, Tatsuki; Revelo, Monica P; Shappell, Scott B; Smith, Jeffrey R; Hayward, Simon W


    Benign prostatic hyperplasia (BPH) and prostate carcinoma (CaP) are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and CaP and which could serve as potential clinical biomarkers. In this study, we used a human prostate xenograft model to define a profile of genes regulated in vivo by androgens, with an emphasis on identifying candidate biomarkers. Benign transition zone (TZ) human prostate tissue from radical prostatectomies was grafted to the sub-renal capsule site of intact or castrated male immunodeficient mice, followed by the removal or addition of androgens, respectively. Microarray analysis of RNA from these tissues was used to identify genes that were; 1) highly expressed in prostate, 2) had significant expression changes in response to androgens, and, 3) encode extracellular proteins. A total of 95 genes meeting these criteria were selected for analysis and validation of expression in patient prostate tissues using quantitative real-time PCR. Expression levels of these genes were measured in pooled RNAs from human prostate tissues with varying severity of BPH pathologic changes and CaP of varying Gleason score. A number of androgen regulated genes were identified. Additionally, a subset of these genes were over-expressed in RNA from clinical BPH tissues, and the levels of many were found to correlate with disease status. Our results demonstrate the feasibility, and some of the problems, of using a mouse xenograft model to characterize the androgen regulated expression profiles of intact human prostate tissues.

  3. Molecular targeting of carbonic anhydrase IX in mice with hypoxic HT29 colorectal tumor xenografts.

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    Sean Carlin

    Full Text Available BACKGROUND: Carbonic anhydrase IX (CAIX is a membrane spanning protein involved in the enzymatic regulation of tumor acid-base balance. CAIX has been shown to be elevated in a number of hypoxic tumor types. The purpose of this study was to determine the efficiency of intact and IgG fragments of cG250 to target CAIX in vivo in a hypoxic tumor model. METHODOLOGY/PRINCIPAL FINDINGS: Conventional biodistribution studies were performed with (111In-DO3A-cG250, (111In-DO3A-F(ab'(2-cG250 and (111In-DO3A-Fab-cG250. Additional ex vivo analysis of the tumor was performed with markers for tumor hypoxia, blood perfusion and endogenous CAIX expression. All four data sets were digitally correlated to determine the optimal agent for determining hypoxia in a HT29 colon cancer xenograft. The HT29 human colorectal tumor xenografts show strong CAIX expression in hypoxic areas of poor blood perfusion. The intact IgG had an initial high focal uptake at the periphery of these hypoxic regions and penetration into the areas of highest CAIX expression over the 7-day study period. The lower molecular weight antibody fragments had a faster uptake into areas of high CAIX expression, but had a much lower absolute uptake at the optimal imaging times. CONCLUSIONS/SIGNIFICANCE: For the clinical detection of hypoxia induced CAIX using cG250 antibody based agents, imaging with the intact IgG at 7 days post injection would allow for the most sensitive and accurate detection of CAIX.

  4. Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts. (United States)

    José, Anabel; Sobrevals, Luciano; Miguel Camacho-Sánchez, Juan; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina


    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p less than 0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.

  5. Benzyl isothiocyanate inhibits epithelial-mesenchymal transition in cultured and xenografted human breast cancer cells. (United States)

    Sehrawat, Anuradha; Singh, Shivendra V


    We showed previously that cruciferous vegetable constituent benzyl isothiocyanate (BITC) inhibits growth of cultured and xenografted human breast cancer cells and suppresses mammary cancer development in a transgenic mouse model. We now show, for the first time, that BITC inhibits epithelial-mesenchymal transition (EMT) in human breast cancer cells. Exposure of estrogen-independent MDA-MB-231 and estrogen-responsive MCF-7 human breast cancer cell lines and a pancreatic cancer cell line (PL-45) to BITC resulted in upregulation of epithelial markers (e.g., E-cadherin and/or occludin) with a concomitant decrease in protein levels of mesenchymal markers, including vimentin, fibronectin, snail, and/or c-Met. The BITC-mediated induction of E-cadherin protein was accompanied by an increase in its transcription, whereas BITC-treated MDA-MB-231 cells exhibited suppression of vimentin, snail, and slug mRNA levels. Experimental EMT induced by exposure to TGFβ and TNFα or Rb knockdown in a spontaneously immortalized nontumorigenic human mammary epithelial cell line (MCF-10A) was also partially reversed by BITC treatment. The TGFβ-/TNFα-induced migration of MCF-10A cells was inhibited in the presence of BITC, which was partially attenuated by RNA interference of E-cadherin. Inhibition of MDA-MB-231 xenograft growth in vivo in female athymic mice by BITC administration was associated with an increase in protein level of E-cadherin and suppression of vimentin and fibronectin protein expression. In conclusion, this study reports a novel anticancer effect of BITC involving inhibition of EMT, a process triggered during progression of cancer to invasive state.

  6. Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models. (United States)

    Leu, Jyh-Der; Wang, Bo-Shen; Chiu, Shu-Jun; Chang, Chun-Yuan; Chen, Chien-Chih; Chen, Fu-Du; Avirmed, Shiirevnyamba; Lee, Yi-Jang


    Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vivo effects of fisetin on tumor growth remain unclear. In the present study a murine xenograft tumor model was employed to investigate the therapeutic effects of fisetin in combination with radiation on CT-26 colon cancer cells and human HCT116 colorectal cancer cells. This revealed that intratumoral injection of fisetin significantly suppressed the growth of CT-26 tumors compared with the untreated control group, but had little effect on the growth of HCT116 tumors. However, fisetin in combination with 2-Gy radiation enhanced tumor suppressor activity in murine colon and human colorectal xenograft tumors, as compared with 2-Gy fractionated radiation administered alone for 5 days and fisetin alone. Interestingly, fisetin downregulated the expression of the oncoprotein securin in a p53-independent manner. However, securin-null HCT116 tumors showed only moderate sensitivity to fisetin treatment, and the combination of fisetin and radiation did not significantly suppress securin-null HCT116 tumor growth compared with normal HCT116 tumors. Therefore, the role of securin in mediating the effect of fisetin on colorectal cancer growth warrants further investigation. In conclusion, the results of the current study provide important preclinical data for evaluating the efficacy of fisetin and radiation combination treatment as an adjuvant chemoradiotherapy for human colorectal cancers.

  7. Near-infrared optical imaging in glioblastoma xenograft with ligand-targeting {alpha}3 integrin

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    Xiao, Wenwu; Yao, Nianhuan; Peng, Li; Liu, Ruiwu; Lam, Kit S. [University of California Davis, Division of Hematology and Oncology, Department of Internal Medicine, UC Davis Cancer Center, Sacramento, CA (United States)


    Patients with glioblastoma usually have a very poor prognosis. Even with a combination of radiotherapy plus temozolomide, the median survival of these patients is only 14.6 months. New treatment approaches to this cancer are needed. Our purpose is to develop new cell surface-binding ligands for glioblastoma cells and use them as targeted imaging and therapeutic agents for this deadly disease. One-bead one-compound combinatorial cyclic peptide libraries were screened with live human glioblastoma U-87MG cells. The binding affinity and targeting specificity of peptides identified were tested with in vitro experiments on cells and in vivo and ex vivo experiments on U-87MG xenograft mouse model. A cyclic peptide, LXY1, was identified and shown to be binding to the {alpha}3 integrin of U-87MG cells with moderately high affinity (K{sub d} = 0.5 {+-} 0.1 {mu}M) and high specificity. Biotinylated LXY1, when complexed with streptavidin-Cy5.5 (SA-Cy5.5) conjugate, targeted both subcutaneous and orthotopic U-87MG xenograft implants in nude mice. The in vivo targeting specificity was further verified by strong inhibition of tumor uptake of LXY1-biotin-SA-Cy5.5 complex when intravenously injecting the animals with anti-{alpha}3 integrin antibody or excess unlabeled LXY1 prior to administrating the imaging probe. The smaller univalent LXY1-Cy5.5 conjugate (2,279 Da) was found to have a faster accumulation in the U-87MG tumor and shorter retention time compared with the larger tetravalent LXY1-biotin-SA-Cy5.5 complex (approximately 64 kDa). Collectively, the data reveals that LXY1 has the potential to be developed into an effective imaging and therapeutic targeting agent for human glioblastoma. (orig.)

  8. Patient-Derived Tumor Xenografts Are Susceptible to Formation of Human Lymphocytic Tumors

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    Gennadiy Bondarenko


    Full Text Available Patient-derived xenograft (PDX tumor models have emerged as a new approach to evaluate the effects of cancer drugs on patients’ personalized tumor grafts enabling to select the best treatment for the cancer patient and providing a new tool for oncology drug developers. Here, we report that human tumors engrafted in immunodeficient mice are susceptible to formation of B-and T-cell PDX tumors. We xenografted human primary and metastatic tumor samples into immunodeficient mice and found that a fraction of PDX tumors generated from patients’ samples of breast, colon, pancreatic, bladder and renal cancer were histologically similar to lymphocytic neoplasms. Moreover, we found that the first passage of breast and pancreatic cancer PDX tumors after initial transplantation of the tumor pieces from the same human tumor graft could grow as a lymphocytic tumor in one mouse and as an adenocarcinoma in another mouse. Whereas subcutaneous PDX tumors resembling human adenocarcinoma histology were slow growing and non-metastatic, we found that subcutaneous PDX lymphocytic tumors were fast growing and formed large metastatic lesions in mouse lymph nodes, liver, lungs, and spleen. PDX lymphocytic tumors were comprised of B-cells which were Epstein-Barr virus positive and expressed CD45 and CD20. Because B-cells are typically present in malignant solid tumors, formation of B-cell tumor may evolve in a wide range of PDX tumor models. Although PDX tumor models show great promise in the development of personalized therapy for cancer patients, our results suggest that confidence in any given PDX tumor model requires careful screening of lymphocytic markers.

  9. The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model.

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    Kiyoshi Takahara

    Full Text Available Boron neutron capture therapy (BNCT is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa using an in vivo mouse xenograft model that we have developed.Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA; Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment.The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean ± SD 6.9 ± 1.5 vs 12.7 ± 4.0, p<0.05, while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment.This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.

  10. beta 1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts

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    Park, Catherine C.; Park, Catherine C.; Zhang, Hui J.; Yao, Evelyn S.; Park, Chong J.; Bissell, Mina J.


    {beta}1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of {beta}1 integrin signaling. We showed previously that {beta}1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix (3D lrECM) cultures and in vivo. Here we asked whether AIIB2 could synergize with IR to modify Akt-mediated IR resistance. We used 3D lrECM cultures to test the optimal combination of AIIB2 with IR treatment of two breast cancer cell lines, MCF-7 and HMT3522-T4-2, as well as T4-2 myr-Akt breast cancer colonies or HMT3522-S-1, which form normal organotypic structures in 3D lrECM. Colonies were assayed for apoptosis and {beta}1 integrin/Akt signaling pathways were evaluated using western blot. In addition, mice bearing MCF-7 xenografts were used to validate the findings in 3D lrECM. We report that AIIB2 increased apoptosis optimally post-IR by down regulating Akt in breast cancer colonies in 3D lrECM. In vivo, addition of AIIB2 after IR significantly enhanced tumor growth inhibition and apoptosis compared to either treatment alone. Remarkably, the degree of tumor growth inhibition using AIIB2 plus 2 Gy radiation was similar to that of 8 Gy alone. We showed previously that AIIB2 had no discernible toxicity in mice; here, its addition allowed for a significant reduction in the IR dose that was necessary to achieve comparable growth inhibition and apoptosis in breast cancer xenografts in vivo.

  11. Growth hormone receptor antagonism suppresses tumour regrowth after radiotherapy in an endometrial cancer xenograft model. (United States)

    Evans, Angharad; Jamieson, Stephen M F; Liu, Dong-Xu; Wilson, William R; Perry, Jo K


    Human GH expression is associated with poor survival outcomes for endometrial cancer patients, enhanced oncogenicity of endometrial cancer cells and reduced sensitivity to ionising radiation in vitro, suggesting that GH is a potential target for anticancer therapy. However, whether GH receptor inhibition sensitises to radiotherapy in vivo has not been tested. In the current study, we evaluated whether the GH receptor antagonist, pegvisomant (Pfizer), sensitises to radiotherapy in vivo in an endometrial tumour xenograft model. Subcutaneous administration of pegvisomant (20 or 100 mg/kg/day, s.c.) reduced serum IGF1 levels by 23% and 68%, respectively, compared to vehicle treated controls. RL95-2 xenografts grown in immunodeficient NIH-III mice were treated with vehicle or pegvisomant (100 mg/kg/day), with or without fractionated gamma radiation (10 × 2.5 Gy over 5 days). When combined with radiation, pegvisomant significantly increased the median time tumours took to reach 3× the pre-radiation treatment volume (49 days versus 72 days; p = 0.001). Immunohistochemistry studies demonstrated that 100 mg/kg pegvisomant every second day was sufficient to abrogate MAP Kinase signalling throughout the tumour. In addition, treatment with pegvisomant increased hypoxic regions in irradiated tumours, as determined by immunohistochemical detection of pimonidazole adducts, and decreased the area of CD31 labelling in unirradiated tumours, suggesting an anti-vascular effect. Pegvisomant did not affect intratumoral staining for HIF1α, VEGF-A, CD11b, or phospho-EGFR. Our results suggest that blockade of the human GH receptor may improve the response of GH and/or IGF1-responsive endometrial tumours to radiation.

  12. Comparative Analysis of Human and Canine Campylobacter upsaliensis Isolates by Amplified Fragment Length Polymorphism

    DEFF Research Database (Denmark)

    Damborg, Peter; Guardabassi, Luca; Pedersen, Karl;


    Human (n = 33) and canine (n = 53) Campylobacter upsaliensis isolates from seven countries were genotyped by a new amplified fragment length polymorphism method. We observed 100% typeability and high overall diversity. The majority of human strains (23/33) clustered separately from canine strains......, indicating that dogs may not be the main source of human infection.......Human (n = 33) and canine (n = 53) Campylobacter upsaliensis isolates from seven countries were genotyped by a new amplified fragment length polymorphism method. We observed 100% typeability and high overall diversity. The majority of human strains (23/33) clustered separately from canine strains...

  13. Feeding ecology and morphology of the upper canines in bears (carnivora: Ursidae). (United States)

    Christiansen, Per


    The morphology and mechanical strength of the upper canines in all eight extant species of ursids is analyzed, and the findings are discussed in relation to feeding ecology. Ursids have proportionally smaller canines than other large carnivores with a specialized feeding ecology, such as large felids, and the upper canine morphology is both canid-like and felid-like. The giant panda is the most divergent species, and its short, blunt, and cone-like canines appear well adapted for tearing into bamboo. The almost equally herbivorous spectacled bear has a less derived canine morphology. The large canines of the sun bear are divergent from other ursine ursids, and may be an adaptation for tearing open tree trunks in search of insects. Discriminant Analysis is successful in separating ursid species on the basis of canine morphology, but the canines of ursine ursids, and also of the spectacled bear, show greater resemblance among the species than the marked differences in feeding ecology would suggest. This could be in part due to a short evolutionary history, and in part due to canines not having been subjected to much evolutionary selection as has been the case among other large carnivores, such as large felids. Ursids are probably evolutionarily and ecologically successful due to physical size and strength rather than a derived craniodental anatomy.

  14. Canine length in wild male baboons: maturation, aging and social dominance rank.

    Directory of Open Access Journals (Sweden)

    Jordi Galbany

    Full Text Available Canines represent an essential component of the dentition for any heterodont mammal. In primates, like many other mammals, canines are frequently used as weapons. Hence, tooth size and wear may have significant implications for fighting ability, and consequently for social dominance rank, reproductive success, and fitness. We evaluated sources of variance in canine growth and length in a well-studied wild primate population because of the potential importance of canines for male reproductive success in many primates. Specifically, we measured maxillary canine length in 80 wild male baboons (aged 5.04-20.45 years from the Amboseli ecosystem in southern Kenya, and examined its relationship with maturation, age, and social dominance rank. In our analysis of maturation, we compared food-enhanced baboons (those that fed part time at a refuse pit associated with a tourist lodge with wild-feeding males, and found that food-enhanced males achieved long canines earlier than wild-feeding males. Among adult males, canine length decreased with age because of tooth wear. We found some evidence that, after controlling for age, longer canines were associated with higher adult dominance rank (accounting for 9% of the variance in rank, but only among relatively high-ranking males. This result supports the idea that social rank, and thus reproductive success and fitness, may depend in part on fighting ability mediated by canine size.

  15. Modularity of the anthropoid dentition: Implications for the evolution of the hominin canine honing complex. (United States)

    Delezene, Lucas K


    In most anthropoid primates, the maxillary canine, mandibular canine, and mesial mandibular premolar form a functional complex that hones the canines. Characters in functional complexes are predicted to covary genetically, which constrains their evolutionary independence. As a result of substantial changes to canine and honing premolar size and shape, hominins are characterized by the apomorphic loss of canine honing. In early hominins, changes in canine and 'honing' premolar size and shape appear to have been uncoordinated, which is unexpected if there is strong genetic covariation coupling these teeth. Using the pattern and magnitude of phenotypic dental size covariation in extant anthropoids, results of this study indicate that certain dimensions of the anthropoid honing complex are characterized by strong size covariation within species and that canine and honing premolar size have evolved in a coordinated manner in both males and females, which undermines arguments that the complex is selectively important only in males. Further, there is no evidence for negative or strong positive covariance between canine and either incisor or postcanine size. If patterns of phenotypic covariation reflect genetic covariation, this suggests that canine reduction was unlikely to have been a dependent change associated with the development of postcanine megadontia or incisor reduction.

  16. Canine length in wild male baboons: maturation, aging and social dominance rank. (United States)

    Galbany, Jordi; Tung, Jenny; Altmann, Jeanne; Alberts, Susan C


    Canines represent an essential component of the dentition for any heterodont mammal. In primates, like many other mammals, canines are frequently used as weapons. Hence, tooth size and wear may have significant implications for fighting ability, and consequently for social dominance rank, reproductive success, and fitness. We evaluated sources of variance in canine growth and length in a well-studied wild primate population because of the potential importance of canines for male reproductive success in many primates. Specifically, we measured maxillary canine length in 80 wild male baboons (aged 5.04-20.45 years) from the Amboseli ecosystem in southern Kenya, and examined its relationship with maturation, age, and social dominance rank. In our analysis of maturation, we compared food-enhanced baboons (those that fed part time at a refuse pit associated with a tourist lodge) with wild-feeding males, and found that food-enhanced males achieved long canines earlier than wild-feeding males. Among adult males, canine length decreased with age because of tooth wear. We found some evidence that, after controlling for age, longer canines were associated with higher adult dominance rank (accounting for 9% of the variance in rank), but only among relatively high-ranking males. This result supports the idea that social rank, and thus reproductive success and fitness, may depend in part on fighting ability mediated by canine size.

  17. Dental anomalies in first-degree relatives of transposed canine probands

    Institute of Scientific and Technical Information of China (English)

    Adriana Bartolo; Neville Calleja; Fraser McDonald; Simon Camilleri


    The aim of this study was to investigate and compare the inheritance pattern and prevalence of inheritable dental anomalies in a sample of patients with maxillary canine—first premolar transposition and their first-degree relatives with a sample of palatally displaced canine families. Thirty-five consecutive maxillary canine—first premolar transposition probands and 111 first-degree relatives were matched to 35 consecutive palatally displaced canine probands and 115 first-degree relatives. These were assessed for palatally displaced canines and incisor-premolar hypodontia. Parental age at birth of the proband was also noted. The results revealed that (i) there is no difference in the overall prevalence of palatally displaced canine or incisor-premolar hypodontia between the groups of relatives; (ii) first-degree relatives of bilateral palatally displaced canine probands have a higher prevalence of palatally displaced canine and incisor-premolar hypodontia than those with unilateral palatally displaced canine; and (iii) maternal age at birth of the maxillary canine—first premolar transposition probands was significantly higher than that of the palatally displaced canine probands. The results suggest that maxillary canine—first premolar transposition and palatally displaced canine are unlikely to be different genetic entities and also indicate environmental or epigenetic influences on dental development.

  18. Dental anomalies in first-degree relatives of transposed canine probands (United States)

    Bartolo, Adriana; Calleja, Neville; McDonald, Fraser; Camilleri, Simon


    The aim of this study was to investigate and compare the inheritance pattern and prevalence of inheritable dental anomalies in a sample of patients with maxillary canine—first premolar transposition and their first-degree relatives with a sample of palatally displaced canine families. Thirty-five consecutive maxillary canine—first premolar transposition probands and 111 first-degree relatives were matched to 35 consecutive palatally displaced canine probands and 115 first-degree relatives. These were assessed for palatally displaced canines and incisor-premolar hypodontia. Parental age at birth of the proband was also noted. The results revealed that (i) there is no difference in the overall prevalence of palatally displaced canine or incisor-premolar hypodontia between the groups of relatives; (ii) first-degree relatives of bilateral palatally displaced canine probands have a higher prevalence of palatally displaced canine and incisor-premolar hypodontia than those with unilateral palatally displaced canine; and (iii) maternal age at birth of the maxillary canine—first premolar transposition probands was significantly higher than that of the palatally displaced canine probands. The results suggest that maxillary canine—first premolar transposition and palatally displaced canine are unlikely to be different genetic entities and also indicate environmental or epigenetic influences on dental development. PMID:25634123

  19. Exposure of pampas fox (Pseudalopex gymnocercus) and crab-eating fox (Cerdocyon thous) from the Southern region of Brazil to Canine distemper virus (CDV), Canine parvovirus (CPV) and Canine coronavirus (CCoV)


    Silvia de Oliveira Hübner; Felipe Geraldes Pappen; Jerônimo Lopes Ruas; Gilberto D'Ávila Vargas; Geferson Fischer; Telmo Vidor


    The exposure of 13 Brazilian free-ranging nondomestic canids (five pampas fox - Pseudalopex gymnocercus and eight crab-eating fox -Cerdocyon thous) from Southern region of Brazil, to Canine distemper virus (CDV), canine parvovirus (CPV) and Canine coronavirus (CCoV) was investigated. Antibodies against CDV were detected in 38.5% (5/13) of the samples. There were anti-CDV antibodies in 60% (3/5) of P. gymnocercus and in 25% (2/8) of C. thous. The frequency was higher among the adults and males...

  20. Characterization of human glioblastoma cell lines in vitro and their xenografts in nude mice by DNA fingerprinting

    DEFF Research Database (Denmark)

    Türeci, O; Fischer, H; Lagoda, P;


    Human gliomas were grown as permanent tissue cultures and xenografts in nude mice. DNA fingerprint patterns from two human gliomas were established using two different hypervariable multilocus probes [( GTG]5 and 33.15). In general the cell lines investigated showed an overall stability in the DNA...

  1. Utility of a human-mouse xenograft model and in vivo near-infrared fluorescent imaging for studying wound healing. (United States)

    Shanmugam, Victoria K; Tassi, Elena; Schmidt, Marcel O; McNish, Sean; Baker, Stephen; Attinger, Christopher; Wang, Hong; Shara, Nawar; Wellstein, Anton


    To study the complex cellular interactions involved in wound healing, it is essential to have an animal model that adequately mimics the human wound microenvironment. Currently available murine models are limited because wound contraction introduces bias into wound surface area measurements. The purpose of this study was to demonstrate utility of a human-mouse xenograft model for studying human wound healing. Normal human skin was harvested from elective abdominoplasty surgery, xenografted onto athymic nude (nu/nu) mice, and allowed to engraft for 3 months. The graft was then wounded using a 2-mm punch biopsy. Wounds were harvested on sequential days to allow tissue-based markers of wound healing to be followed sequentially. On the day of wound harvest, mice were injected with XenoLight RediJect cyclooxygenase-2 (COX-2) probe and imaged according to package instructions. Immunohistochemistry confirms that this human-mouse xenograft model is effective for studying human wound healing in vivo. Additionally, in vivo fluorescent imaging for inducible COX-2 demonstrated upregulation from baseline to day 4 (P = 0·03) with return to baseline levels by day 10, paralleling the reepithelialisation of the wound. This human-mouse xenograft model, combined with in vivo fluorescent imaging provides a useful mechanism for studying molecular pathways of human wound healing.

  2. Systemic treatment of xenografts with vaccinia virus GLV-1h68 reveals the immunologic facet of oncolytic therapy

    Directory of Open Access Journals (Sweden)

    Liu Hui


    Full Text Available Abstract Background GLV-1h68 is an attenuated recombinant vaccinia virus (VACV that selectively colonizes established human xenografts inducing their complete regression. Results Here, we explored xenograft/VACV/host interactions in vivo adopting organism-specific expression arrays and tumor cell/VACV in vitro comparing VACV replication patterns. There were no clear-cut differences in vitro among responding and non-responding tumors, however, tumor rejection was associated in vivo with activation of interferon-stimulated genes (ISGs and innate immune host's effector functions (IEFs correlating with VACV colonization of the xenografts. These signatures precisely reproduce those observed in humans during immune-mediated tissue-specific destruction (TSD that causes tumor or allograft rejection, autoimmunity or clearance of pathogens. We recently defined these common pathways in the "immunologic constant of rejection" hypothesis (ICR. Conclusion This study provides the first prospective validation of a universal mechanism associated with TSD. Thus, xenograft infection by oncolytic VACV, beyond offering a promising therapy of established cancers, may represent a reliable pre-clinical model to test therapeutic strategies aimed at modulating the central pathways leading to TSD; this information may lead to the identification of principles that could refine the treatment of cancer and chronic infection by immune stimulation or autoimmunity and allograft rejection through immune tolerance.

  3. Biodistribution and imaging of FDG in rats with LS174T carcinoma xenografts and focal Escherichia coli infection.

    NARCIS (Netherlands)

    Kok, P.J.; Eerd-Vismale, J.E.M. van; Boerman, O.C.; Corstens, F.H.M.; Oyen, W.J.G.


    OBJECTIVE: The aim of this study was to compare the dynamic distribution of fluorodeoxyglucose (FDG) in malignant and in infectious lesions. METHODS: The dynamic distribution of FDG was studied in Rowett nude (RNU) rats with a LS174T carcinoma xenograft in the left front leg and an Escherichia coli-

  4. Canine trypanosomiasis: etiology of infection and implications for public health

    Directory of Open Access Journals (Sweden)

    LJ Eloy


    Full Text Available Canine trypanosomiasis, caused by protozoans of the genus Trypanosoma, is divided into two primary types: the American form (Chagas disease, due to Trypanosoma cruzi infection, and the African form (sleeping sickness or surra, provoked by Trypanosomaevansi. This disease was originally enzootic and affected only wild animals, including mammals and birds, which served as reservoirs. Later, it spread to domestic animals such as horses, cattle and dogs. The disease became a zoonosis when contact between rural inhabitants and natural Trypanosoma foci occurred, due to ecological imbalances and increasing migration. Dogs are significantly involved in this context, because they are the main domestic animals and participate in the transmission and maintenance cycles of these parasites. This article reports etiological, epidemiological and public health aspects of canine trypanosomiasis, and the most important peculiarities of this zoonosis in dogs.

  5. Canine tooth wear in captive little brown bats (United States)

    Clark, D.R.


    Upper canine teeth of little brown bats Myotis lucifugus lucifugus held in stainless steel wire mesh cages underwent severe wear which exceeded that observed previously in caged big brown bats, Eptesicus fuscus fuscus. This suggests a relationship between amount of wear and size of the caged bats with damage increasing as size decreases. Rapid wear of canine teeth by little brown bats resembled that observed in big brown bats in that it was limited to the first 2 weeks of captivity. This result indicates a universal interval for acclimation to cage conditions among vespertilionid bats. Dietary toxicants DDE and PCB did not affect the extent of wear. If bats are to be released to the wild, confinement in wire mesh cages should be avoided.

  6. Survey of Canine Dirofilaria immitis Infection in New Caledonia

    Directory of Open Access Journals (Sweden)

    S. Watier-Grillot


    Full Text Available 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 (RIM test: WITNESS DIROFILARIA (Synbiotics Europe. Blood samples were collected from 64 dogs: 49 strays and 15 military working dogs. The military dogs received a permanent chemoprophylaxis (moxidectin. In 11 stray dogs, both tests were positive (22.4%. All the military dogs were negative, showing efficiency of chemoprophaxis. Results were discrepant in 6 dogs, negative with one test and doubtful with the other. Antigen heartworm test kits are available and reliable diagnostic tools. They are useful to evaluate the efficiency of chemoprophylaxis and to detect infected animals in order to treat them and to prevent the spreading of the disease.

  7. An Update on Therapeutic Management of Canine Demodicosis

    Directory of Open Access Journals (Sweden)

    S. K. Singh


    Full Text Available Canine demodicosis is a common noncontagious parasitic dermatosis caused by different spp of Demodex mites including Demodex canis, Demodex injai and D. cornei. Generalized demodicosis can be one of the most frustrating skin diseases, one will ever treat. Conventional and newer miticidal therapies are available to veterinarian to treat this frustrating skin disease. All recognized Demodex mites in dogs appear to respond similarly to mite targeted therapy. Treatment for canine demodicosis includes amitraz, ivermectin, milbemicin oxime, moxidectin, and doramectin. The use of any glucocorticoid-containing products is contraindicated and could favour disease generalization. Conventional treatments will often appear to work however, but it relies heavily on a highly toxic method of treatment. Using natural remedies for mange, on the other hand, can enhance the dog’s immune system, so that the body can fight off the mange mite infection by itself. [Veterinary World 2011; 4(1.000: 41-44

  8. Canine hepatozoonosis in Brazil: description of eight naturally occurring cases. (United States)

    Gondim, L F; Kohayagawa, A; Alencar, N X; Biondo, A W; Takahira, R K; Franco, S R


    Eight cases of canine hepatozoonosis were diagnosed at the Veterinary Hospital (Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual Paulista, Campus de Botucatu), between October 1993 and April 1994. Clinical signs included anorexia, pale mucous membranes, weight loss, pain, diarrhoea, vomit, gait abnormalities, fever, polyuria and polydipsia. Haematologic findings revealed anaemia in seven cases, leucocytosis with neutrophilia in three cases, lymphopenia in three cases and monocytosis in four cases. Serum biochemistries included alterations in many parameters. The micrometry of Hepatozoon canis gametocytes ranged from 6.8 x 4.0 microns to 7.5 x 4.5 microns. Parasitaemia ranged from less than 0.5% to 2%. In all the cases reported other concurrent diseases were present. Diagnosis of canine hepatozoonosis was made by identifying H. canis gametocytes within leucocytes in stained blood smears.

  9. Evaluation of a sponge-on therapy for canine scabies. (United States)

    Folz, S D; Kratzer, D D; Kakuk, T J; Rector, D L


    Forty dogs (20 treated, 20 controls) were utilized to evaluate a new treatment for naturally acquired canine scabies. A liquid concentrate formulation of amitraz was diluted and applied as a sponge-on therapy. Ninety-four percent of the dogs treated with the scabicide were cleared of mites and returned to clinical normality with a single topical treatment; one dog was retreated, cleared of mites and was also returned to normality. All dogs treated with the miticide responded clinically, therefore the treatment also may be useful when trial therapy is necessary to differentially diagnose the disease. The miticide was well tolerated by all dogs, and there was no evidence of dermal or ocular irritation. Topical treatment with the liquid concentrate was efficacious and safe as a therapy for naturally acquired canine scabies. Placebo controls did not improve clinically and these animals retained their mite populations.

  10. The unerupted maxillary canine - a post-surgical review.

    LENUS (Irish Health Repository)

    O'Dowling, Ian


    The orthodontic records of 685 patients referred for surgical exposure of an unerupted impacted maxillary canine tooth were examined. The condition was more common among females than males, slightly less than 2:1. The impacted teeth had a palatal-labial ratio of 3:1. All of the teeth were exposed using the open surgical technique and in 98% of cases the tooth erupted and was orthodontically aligned. In 2% of cases ankylosis occurred and the teeth were subsequently extracted. The presence of peg-shaped lateral incisors associated with the impacted maxillary canine tooth was 3.4% of the total number of impacted teeth and congenital absence was found in 1.7% of impacted teeth.

  11. Serotonin transporter and dopamine transporter imaging in the canine brain

    Energy Technology Data Exchange (ETDEWEB)

    Peremans, Kathelijne [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Goethals, Ingeborg [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium); De Vos, Filip [Laboratory of Radiopharmacy, Pharmaceutical Sciences, Ghent University, B-9000 Ghent (Belgium); Dobbeleir, A. [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Ham, Hamphrey [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium); Van Bree, Henri [Department of Medical Imaging, Faculty of Veterinary Sciences, Ghent University, B-9000 Ghent (Belgium); Heeringen, Cees van [Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, B-9000, Ghent (Belgium); Audenaert, Kurt [Division of Nuclear Medicine, University Hospital Ghent, B-9000 Ghent (Belgium) and Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, B-9000, Ghent (Belgium)]. E-mail:


    The serotonergic and dopaminergic systems are involved in a wide range of emotional and behavioral aspects of animals and humans and are involved in many neuropsychiatric disorders. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are designed to block the 5-HT transporter (SERT), thereby increasing the available 5-HT in the brain. Functional imaging with specific SERT and dopamine transporter (DAT) ligands contributes to the study of the SSRI-transporter interaction. First, we evaluated the feasibility of a canine model in the study of the SERT and DAT with the radioligands [{sup 123}I]-{beta}-CIT and [{sup 123}I]-FP-CIT as well as single-photon emission computed tomography imaging. Second, we studied the effect of SSRIs (sertraline, citalopram and escitalopram) on the SERT and DAT in two dogs. The position of the canine model in the study of the SERT and DAT is discussed and compared with other animal models.

  12. Canine parvovirus effect on wolf population change and pup survival (United States)

    Mech, L.D.; Goyal, S.M.


    Canine parvovirus infected wild canids more than a decade ago, but no population effect has been documented. In wild Minnesota wolves (Canis lupus) over a 12-yr period, the annual percent population increase and proportion of pups each were inversely related to the percentage of wolves serologically positive to the disease. Although these effects did not seem to retard this large extant population, similar relationships in more isolated wolf populations might hinder recovery of this endangered and threatened species.

  13. Management of chemical burns of the canine cornea


    Christmas, Richard


    Significant clinical signs and general principles of treatment for chemical burns of the canine cornea are presented using three typical case studies for illustration. Alkali burns are more common in dogs than acid burns. The sources of alkali in this study were soap, cement, and mortar dust. Common signs of chemical burns are ocular pain, corneal ulceration, tear film inadequacy, corneal edema, and marked corneal neovascularity. Successful treatment requires thorough ocular lavage, treatment...

  14. Clinical systemic lupeol administration for canine oral malignant melanoma


    YOKOE, INORU; AZUMA, Kazuo; Hata, Keishi; MUKAIYAMA, TOSHIYUKI; Goto, Takahiro; Tsuka, Takeshi; Imagawa, Tomohiro; ITOH, Norihiko; Murahata, Yusuke; Osaki, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu


    Canine oral malignant melanoma (COMM) is the most aggressive malignant tumor in dogs. Lupeol is a triterpene extracted from various fruits and vegetables that reportedly inhibits melanoma cell proliferation in vitro and in vivo. In this study, the efficacy of subcutaneous lupeol for spontaneous COMM was evaluated. A total of 11 dogs (3, 5 and 3 dogs diagnosed with clinical stage I, II and III melanoma, respectively) were evaluated. Subcutaneous lupeol (10 mg/kg) was administered postoperative...

  15. Feline and Canine Coronaviruses: Common Genetic and Pathobiological Features


    Sophie Le Poder


    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 ...

  16. Modified Dento - Alveolar Distraction Osteogenesis Technique for Rapid Canine Retraction

    Directory of Open Access Journals (Sweden)

    Sameer Patil


    Full Text Available Distraction Osteogenesis claims to reduce the duration of treatment as well aid in conservation of anchorage. With the introduction of Dento- alveolar distraction retraction of canine can now be done in about 2-3 weeks with minimal loss of anchorage and little/no root resorption. However, surgical procedure required for dento-alveolar distraction can cause significant swelling and post operative discomfort. Our small modification in the surgical procedure drastically reduces the discomfort and improves patient compliance.

  17. Modified Dento - Alveolar Distraction Osteogenesis Technique for Rapid Canine Retraction


    Sameer Patil; Sharadindu Kotrashetti; Sumit Yadev; Ketan Vhora


    Distraction Osteogenesis claims to reduce the duration of treatment as well aid in conservation of anchorage. With the introduction of Dento- alveolar distraction retraction of canine can now be done in about 2-3 weeks with minimal loss of anchorage and little/no root resorption. However, surgical procedure required for dento-alveolar distraction can cause significant swelling and post operative discomfort. Our small modification in the surgical procedure drastically reduces the discomfort an...

  18. Systemic canine histoplasmosis: A case report from Ecuador. (United States)

    Ortiz-Yépez, Julio R; Ortega-Paredes, David A; Barba, Pedro M; Mafla-Endara, Paola M; Zurita, Jeannete


    Histoplasmosis is a zoonotic systemic mycosis caused by Histoplasma capsulatum. We report a case of a female canine, 4 years old, presenting multifocal lymphadenitis and skin and gingival lesions, in Ecuador. Based on cytological, histopathological, histochemical analyses, fungal culture and DNA sequencing of the ITS region of the fungus, the diagnosis confirmed the presence of H. capsulatum as the agent of infection. The treatment plan included ketoconazole with a satisfactory outcome.

  19. Electronic nose versus canine nose : clash of the titans


    Ramesh P. Arasaradnam; Nwokolo, Chuka U.; Bardhan, Karna Dev; Covington, James A.


    We read with great interest the article by Sonoda et al published on line (Gut doi:10.1136/gut.2010.218305) of canine scent detection in those with colorectal cancer. The concept of using a dog to detect diseases is not new; there are many reported incidents of dogs barking at their owners (or even trying to bite the leg off of an owner with melanoma!) who are later shown to have the disease.

  20. Canine aggression toward people: a guide for practitioners. (United States)

    Sueda, Karen Lynn C; Malamed, Rachel


    This article reviews the various causes of human-directed aggression in dogs and provides a step-by-step plan guiding the general practitioner through history taking, behavior observations, diagnosis, consultation, treatment, and follow-up care. Charts summarizing how to obtain behavioral information, the client's management options, treatment recommendations, diagnosis and treatment of human-directed aggression, and the clinician's role in preventing human-directed aggression are included. A graphic illustration of canine body language is also provided.

  1. Canine and feline nephrolithiasis. Epidemiology, detection, and management. (United States)

    Ross, S J; Osborne, C A; Lulich, J P; Polzin, D J; Ulrich, L K; Koehler, L A; Bird, K A; Swanson, L L


    Calcium oxalate (39%) and struvite (33%) were the predominant mineral types in canine nephroliths submitted to the Minnesota Urolith Center. Urate salts (12%) and calcium phosphate (2%) occurred less frequently. Provided they are not causing obstruction, struvite nephroliths may be dissolved with medical protocols. Although there are no dissolution protocols for nephroliths containing calcium, risk-benefit ratios should be considered before proceeding with surgery.

  2. Feline and canine coronaviruses : common genetic and pathobiological features


    Sophie Le Poder


    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 ...

  3. Histamine concentration is involved in canine valvular disease


    Mitsuhiro Isaka; Masahiko Befu; Nami Matsubara; Mayuko Ishikawa; Yurie Arase; Shinichi Namba


    It has been known since many years that there are histamine receptors (H) in the heart. Histamines display chronotropic and inotropic activity, cardiovascular diseases, and are thought to be a systemic inflammatory disease. During heart failure, the histamine concentration is elevated. In addition, H2 blockers prolonged the survival period for human patients with heart failure. The aim of this study was to evaluate whether blood concentration of histamine is associated with canine valvular di...

  4. Diagnosis, prevention, and management of canine hip dysplasia: a review

    Directory of Open Access Journals (Sweden)

    Schachner ER


    Full Text Available Emma R Schachner, Mandi J Lopez Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA Abstract: Canine hip dysplasia (CHD is a polygenic and multifactorial developmental disorder characterized by coxofemoral (hip joint laxity, degeneration, and osteoarthritis (OA. Current diagnostic techniques are largely subjective measures of joint conformation performed at different stages of development. Recently, measures on three-dimensional images generated from computed tomography scans predicted the development of OA associated with CHD. Continued refinement of similar imaging methods may improve diagnostic imaging techniques to identify dogs predisposed to degenerative hip joint changes. By current consensus, joint changes consistent with CHD are influenced by genetic predisposition as well as environmental and biomechanical factors; however, despite decades of work, the relative contributions of each to the development and extent of CHD signs remain elusive. Similarly, despite considerable effort to decipher the genetic underpinnings of CHD for selective breeding programs, relevant genetic loci remain equivocal. As such, prevention of CHD within domestic canine populations is marginally successful. Conservative management is often employed to manage signs of CHD, with lifelong maintenance of body mass as one of the most promising methods. Surgical intervention is often employed to prevent joint changes or restore joint function, but there are no gold standards for either goal. To date, all CHD phenotypes are considered as a single entity in spite of recognized differences in expression and response to environmental conditions and treatment. Identification of distinct CHD phenotypes and targeting evidence-based conservative and invasive treatments for each may significantly advance prevention and management of a prevalent, debilitating condition in canine companions. Keywords: canine

  5. Inhibitory effect of celecoxib combined with cisplatin on growth of human tongue squamous carcinoma Tca8113 cell xenograft tumor

    Institute of Scientific and Technical Information of China (English)

    Weizhong Li; Xiaoyan Wang; Zuguo Li; Yanqing Ding


    Objective:The aim of this study was to observe the inhibitory effect of application of COX-2 inhibitor,celecoxib,combined with cisplatin on the growth of human tongue squamous carcinoma Tca8113 cell xenograft by animal experiment.Methods:The nude mice were transplanted subcutaneously with Tca 8113 cells,and then were administrated with celecoxib,cisplatin or celecoxib combined with cisplatin respectively,and were sacrificed after 35 days.The weight of xenograft was measured to calculate the tumor inhibition rate.The histological change was studied under light and electron microscope.The COX-2 protein expression was observed by immunohistological staining.And the COX-2 mRNA expression was determined by RT-PCR.Results:Celecoxib,the COX-2 inhibitor,could not only inhibit the growth of Tca8113 cell xenograft tumor and COX-2 protein expression,but also enhance the inhibitory effect cisplatin on xenograft tumor growth significantly.The tumor inhibition rates of celecoxib group,cisplatin group and celecoxib plus cisplatin group were 15.63%,37.50% and 82.81%respectively that was statistically significant compared to control group(P < 0.01).The combined application of celecoxib and dsplatin could inhibit tumor growth more significantly than that of separated application(P < 0.01).The inhibitory effect of celecoxib on COX-2 mRNA expression of Tca 8113 cell was weaker and not significant(P= 0.073).Conclusion:Celecoxib can not only inhibit xenograft tumor growth in nude mice,but also enhance the inhibitory effect of CDDP on Tca 8113 trans planted tumor growth in nude mice.The mechanism maybe related to inhibition of COX-2 protein expression,which offers beneficial reference to further explore the mechanism between inhibition of COX-2 enzyme activity and prevention of head and neck tumor.

  6. Cetuximab intensifies the ADCC activity of adoptive NK cells in a nude mouse colorectal cancer xenograft model (United States)

    Chen, Shanshan; Li, Xuechun; Chen, Rongming; Yin, Mingang; Zheng, Qiuhong


    Natural killer (NK) cells, discovered ~40 years ago, are believed to be the most effective cytotoxic lymphocytes to counteract cancer; however, adoptive NK cell therapy in vivo has encountered certain limitations, including a lack of specificity. The drug cetuximab can mediate antibody dependent cell mediated cytotoxicity (ADCC) activity through NK cells in vivo, and has been approved for the first-line treatment of epidermal growth factor receptor (EGFR)-positive metastatic colorectal cancer (CRC). However, the ADCC activity of adoptive NK cells, induced by cetuximab in a nude mouse CRC xenograft model, has not been previously reported. The aim of the present study was to explore the ADCC activity of cetuximab combined with adoptive NK cells in CRC xenograft models with various EGFR expressions. The nude mouse xenograft models were established by subcutaneously injecting LOVO or SW620 cells. The mice were then randomly divided into 6 groups: Phosphate-buffered saline, cetuximab, human immunoglobulin G (hIgG), NK cells, hIgG plus NK cells and cetuximab plus NK cells. The ADCC antitumor activity was evaluated in these CRC models. The results indicated that the cetuximab plus NK cells group showed the greatest tumor inhibition effect compared with the NK cells group in LOVO xenograft tumor models with positive EGFR expression. However, the combination of cetuximab and NK cells did not show a stronger tumor inhibitory effect against the SW620 xenograft tumor models compared with the efficiency of NK cells. In conclusion, cetuximab could intensify the ADCC antitumor activity of adoptive NK cells towards CRC with an increased EGFR expression. The combination of cetuximab and NK cells may be a potential immunotherapy for metastatic CRC patients with positive EGFR expression. PMID:27602116

  7. Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy. (United States)

    Valiulienė, Giedrė; Treigytė, Gražina; Savickienė, Jūratė; Matuzevičius, Dalius; Alksnė, Milda; Jarašienė-Burinskaja, Rasa; Bukelskienė, Virginija; Navakauskas, Dalius; Navakauskienė, Rūta


    Xenograft models are suitable for in vivo study of leukemia's pathogenesis and the preclinical development of anti-leukemia agents but understanding of epigenetic regulatory mechanisms linking to adult cell functions in pathological conditions during different in vivo treatments is yet unknown. In this study, for the first time epigenetic chromatin modifications were characterized in tissues and tumours from murine xenograft model generated using the human acute promyelocytic leukemia (APL) NB4 cells engrafted in immunodeficient NOG mice. Xenografts were subjected to combined epigenetic treatment by histone deacetylase inhibitor Belinostat, histone methyltransferase inhibitor 3-DZNeaplanocin A and all-trans-retinoic acid based on in vitro model, where such combination inhibited NB4 cell growth and enhanced retinoic acid-induced differentiation to granulocytes. Xenotransplantation was assessed by peripheral blood cells counts, the analysis of cell surface markers (CD15, CD33, CD45) and the expression of certain genes (PML-RAR alpha, CSF3, G-CSFR, WT1). The combined treatment prolonged APL xenograft mice survival and prevented tumour formation. The analysis of the expression of histone marks such as acetylation of H4, trimethylation of H3K4, H3K9 and H3K27 in APL xenograft mice tumours and tissues demonstrated tissue-specific changes in the level of histone modifications and the APL prognostic mark, WT1 protein. In summary, the effects of epigenetic agents used in this study were positive for leukemia prevention and linked to a modulation of the chromatin epigenetic environment in adult tissues of malignant organism.

  8. Therapeutic Efficacy Assessment of CK6, a Monoclonal KIT Antibody, in a Panel of Gastrointestinal Stromal Tumor Xenograft Models

    Directory of Open Access Journals (Sweden)

    Thomas Van Looy


    Full Text Available We evaluated the efficacy of CK6, a KIT monoclonal antibody, in a panel of human gastrointestinal stromal tumor (GIST xenograft models. Nude mice were bilaterally transplanted with human GIST xenografts (four patient derived and two cell line derived, treated for 3 weeks, and grouped as follows: control (untreated; CK6 (40 mg/kg, 3× weekly; imatinib (50 mg/kg, twice daily; sunitinib (40 mg/kg, once daily; imatinib + CK6; sunitinib + CK6 (same doses and schedules as in the single-agent treatments. Tumor volume assessment, Western blot analysis, and histopathology were used for evaluation of efficacy. Statistical analysis was performed using Mann-Whitney U (MWU and Wilcoxon matched-pairs tests. CK6 as a single agent only reduced tumor growth rate in the UZLX-GIST3 model (P = .053, MWU compared to control, while in none of the other GIST models an effect on tumor growth rate was observed. CK6 did not result in significant anti-proliferative or pro-apoptotic effects in any of the GIST models, and moreover, CK6 did not induce a remarkable inhibition of KIT activation. Furthermore, no synergistic effect of combining CK6 with tyrosine kinase inhibitors (TKIs was observed. Conversely, in certain GIST xenografts, anti-tumor effects seemed to be inferior under combination treatment compared to single-agent TKI treatment. In the GIST xenografts tested, the anti-tumor efficacy of CK6 was limited. No synergy was observed on combination of CK6 with TKIs in these GIST models. Our findings highlight the importance of using relevant in vivo human tumor xenograft models in the preclinical assessment of drug combination strategies.

  9. mtDNA depletion confers specific gene expression profiles in human cells grown in culture and in xenograft

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    Ramaswamy Krishna


    Full Text Available Abstract Background Interactions between the gene products encoded by the mitochondrial and nuclear genomes play critical roles in eukaryotic cellular function. However, the effects mitochondrial DNA (mtDNA levels have on the nuclear transcriptome have not been defined under physiological conditions. In order to address this issue, we characterized the gene expression profiles of A549 lung cancer cells and their mtDNA-depleted ρ0 counterparts grown in culture and as tumor xenografts in immune-deficient mice. Results Cultured A549 ρ0 cells were respiration-deficient and showed enhanced levels of transcripts relevant to metal homeostasis, initiation of the epithelial-mesenchymal transition, and glucuronidation pathways. Several well-established HIF-regulated transcripts showed increased or decreased abundance relative to the parental cell line. Furthermore, growth in culture versus xenograft has a significantly greater influence on expression profiles, including transcripts involved in mitochondrial structure and both aerobic and anaerobic energy metabolism. However, both in vitro and in vivo, mtDNA levels explained the majority of the variance observed in the expression of transcripts in glucuronidation, tRNA synthetase, and immune surveillance related pathways. mtDNA levels in A549 xenografts also affected the expression of genes, such as AMACR and PHYH, involved in peroxisomal lipid metabolic pathways. Conclusion We have identified mtDNA-dependent gene expression profiles that are shared in cultured cells and in xenografts. These profiles indicate that mtDNA-depleted cells could provide informative model systems for the testing the efficacy of select classes of therapeutics, such as anti-angiogenesis agents. Furthermore, mtDNA-depleted cells grown culture and in xenografts provide a powerful means to investigate possible relationships between mitochondrial activity and gene expression profiles in normal and pathological cells.

  10. Penetration of ASM 981 in canine skin: a comparative study. (United States)

    Gutzwiller, Meret E Ricklin; Reist, Martin; Persohn, Elke; Peel, John E; Roosje, Petra J


    ASM 981 has been developed for topical treatment of inflammatory skin diseases. It specifically inhibits the production and release of pro-inflammatory cytokines. We measured the skin penetration of ASM 981 in canine skin and compared penetration in living and frozen skin. To make penetration of ASM 981 visible in dog skin, tritium labelled ASM 981 was applied to a living dog and to defrosted skin of the same dog. Using qualitative autoradiography the radioactive molecules were detected in the lumen of the hair follicles until the infundibulum, around the superficial parts of the hair follicles and into a depth of the dermis of 200 to 500 microm. Activity could not be found in deeper parts of the hair follicles, the dermis or in the sebaceous glands. Penetration of ASM 981 is low in canine skin and is only equally spread in the upper third of the dermis 24 hours after application. Penetration in frozen skin takes even longer than in living canine skin but shows the same distribution.

  11. First report: Yersinia enterocolitica recovered from canine tonsils. (United States)

    Murphy, Brenda P; Drummond, Niall; Ringwood, Tamara; O'Sullivan, Edmund; Buckley, James F; Whyte, Paul; Prentice, Mike B; Fanning, Séamus


    Yersinia enterocolitica (Y. enterocolitica) is a known zoonotic pathogen and is often found in pig tonsils as the primary site of colonisation. In this study we investigated whether or not Y. enterocolitica could be recovered from canine tonsils. During a study on the prevalence of Y. enterocolitica in animal populations in Ireland, 144 canine tonsils and 72 canine rectal swabs were procured over a ten-month period and subjected to microbiological examination for the presence of this human pathogen. Molecular methods were used to determine virulence and all strains were negative for the chromosomally mediated virulence factor (ail) and plasmid-encoded adhesion molecule (pYad). Y. enterocolitica was recovered from 25 of 216 (12%) samples. Twenty-four strains were from tonsils along with one from a rectal swab. All were biotype 1A. Antimicrobial resistance profiling showed two of 25 (8%) were resistant to cephalothin and the remaining strains were resistant to ampicillin and cephalothin with six of these additionally resistant to streptomycin. Our evidence that a human pathogen may be harboured in the oral cavity of dogs' adds a new dimension to the epidemiology of this organism, identifying a potential public health risk following exposure to dogs.

  12. Appearance of the canine meninges in subtraction magnetic resonance images. (United States)

    Lamb, Christopher R; Lam, Richard; Keenihan, Erin K; Frean, Stephen


    The canine meninges are not visible as discrete structures in noncontrast magnetic resonance (MR) images, and are incompletely visualized in T1-weighted, postgadolinium images, reportedly appearing as short, thin curvilinear segments with minimal enhancement. Subtraction imaging facilitates detection of enhancement of tissues, hence may increase the conspicuity of meninges. The aim of the present study was to describe qualitatively the appearance of canine meninges in subtraction MR images obtained using a dynamic technique. Images were reviewed of 10 consecutive dogs that had dynamic pre- and postgadolinium T1W imaging of the brain that was interpreted as normal, and had normal cerebrospinal fluid. Image-anatomic correlation was facilitated by dissection and histologic examination of two canine cadavers. Meningeal enhancement was relatively inconspicuous in postgadolinium T1-weighted images, but was clearly visible in subtraction images of all dogs. Enhancement was visible as faint, small-rounded foci compatible with vessels seen end on within the sulci, a series of larger rounded foci compatible with vessels of variable caliber on the dorsal aspect of the cerebral cortex, and a continuous thin zone of moderate enhancement around the brain. Superimposition of color-encoded subtraction images on pregadolinium T1- and T2-weighted images facilitated localization of the origin of enhancement, which appeared to be predominantly dural, with relatively few leptomeningeal structures visible. Dynamic subtraction MR imaging should be considered for inclusion in clinical brain MR protocols because of the possibility that its use may increase sensitivity for lesions affecting the meninges.

  13. Video otoscopy as a diagnostic tool for canine otoacariasis. (United States)

    de Souza, Clarissa Pimentel; Verocai, Guilherme Gomes; Balbi, Margareth; Scott, Fabio Barbour


    Canine otoacariasis, or otodectic mange, is a common parasitic disorder of dogs' ear canals caused by the mite Otodectes cynotis. Infestation can be detected through diverse protocols of varying sensitivity. We evaluated the use of video otoscopy in comparison with conventional otoscopy and cerumen examination under a microscope for diagnosing O. cynotis in dogs. Thirty-five dogs were evaluated bilaterally for the presence of ear mites, using a veterinary otoscope (Gowlands®), a video otoscope (Welch Allyn®) and the gold-standard technique of examination of swab-collected cerumen under a microscope. Each ear was considered to represent one sample, and 69 ears were examined, since one dog presented with one completely stenotic ear canal. Ear mites were diagnosed in 59.42% (41/69) through video otoscopy. The same 41 infested ear canals were detected by means of cerumen examination under a microscope, whereas conventional otoscopy was able to diagnose mites in only 39.13% (27/69). This difference was statistically significant (p < 0.001). Video otoscopy proved to be superior to conventional otoscopy, and equivalent to the gold standard for detection of O. cynotis in canine ear canals, and should be recommended for controlled trials on drug efficacy for treatment of canine otoacariasis.

  14. Biotinylated dextran amine anterograde tracing of the canine corticospinal tract

    Institute of Scientific and Technical Information of China (English)

    Xiao Han; Guangming Lv; Huiqun Wu; Dafeng Ji; Zhou Sun; Yaofu Li; Lemin Tang


    In this study, biotinylated dextran amine (BDA) was microinjected into the left cortical motor area of the canine brain. Fluorescence microscopy results showed that a large amount of BDA-labeled pyramidal cells were visible in the left cortical motor area after injection. In the left medulla oblongata, the BDA-labeled corticospinal tract was evenly distributed, with green fluorescence that had a clear boundary with the surrounding tissue. The BDA-positive corticospinal tract entered into the right lateral funiculus of the spinal cord and descended into the posterior part of the right lateral funiculus, close to the posterior horn, from cervical to sacral segments. There was a small amount of green fluorescence in the sacral segment. The distribution of BDA labeling in the canine central nervous system was consistent with the course of the corticospinal tract. Fluorescence labeling for BDA gradually diminished with time after injection. Our findings indicate that the BDA anterograde tracing technique can be used to visualize the localization and trajectory of the corticospinal tract in the canine central nervous system.

  15. Validation of a Model for Teaching Canine Fundoscopy. (United States)

    Nibblett, Belle Marie D; Pereira, Mary Mauldin; Williamson, Julie A; Sithole, Fortune


    A validated teaching model for canine fundoscopic examination was developed to improve Day One fundoscopy skills while at the same time reducing use of teaching dogs. This novel eye model was created from a hollow plastic ball with a cutout for the pupil, a suspended 20-diopter lens, and paint and paper simulation of relevant eye structures. This eye model was mounted on a wooden stand with canine head landmarks useful in performing fundoscopy. Veterinary educators performed fundoscopy using this model and completed a survey to establish face and content validity. Subsequently, veterinary students were randomly assigned to pre-laboratory training with or without the use of this teaching model. After completion of an ophthalmology laboratory on teaching dogs, student outcome was assessed by measuring students' ability to see a symbol inserted on the simulated retina in the model. Students also completed a survey regarding their experience with the model and the laboratory. Overall, veterinary educators agreed that this eye model was well constructed and useful in teaching good fundoscopic technique. Student performance of fundoscopy was not negatively impacted by the use of the model. This novel canine model shows promise as a teaching and assessment tool for fundoscopy.

  16. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

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    K. Jayasri


    Full Text Available Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS, glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175% was found to be increased, whereas glucose-6-phosphatase (33%, fructose-1, 6-bisphosphatase (42%, and G6PD (5 fold activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors.

  17. Refinement of the canine CD1 locus topology and investigation of antibody binding to recombinant canine CD1 isoforms

    DEFF Research Database (Denmark)

    Schjaerff, Mette; Keller, Stefan M; Fass, Joseph;


    CD1 molecules are antigen-presenting glycoproteins primarily found on dendritic cells (DCs) responsible for lipid antigen presentation to CD1-restricted T cells. Despite their pivotal role in immunity, little is known about CD1 protein expression in dogs, notably due to lack of isoform-specific a......CD1 molecules are antigen-presenting glycoproteins primarily found on dendritic cells (DCs) responsible for lipid antigen presentation to CD1-restricted T cells. Despite their pivotal role in immunity, little is known about CD1 protein expression in dogs, notably due to lack of isoform......-specific antibodies. The canine (Canis familiaris) CD1 locus was previously found to contain three functional CD1A genes: canCD1A2, canCD1A6, and canCD1A8, where two variants of canCD1A8, canCD1A8.1 and canCD1A8.2, were assumed to be allelic variants. However, we hypothesized that these rather represented two...... recognized canine CD1a8 and CD1a9 isoforms, and Fe1.5F4 mAb solely recognized canine CD1a6. Anti-CD1b mAbs recognized the canine CD1b protein, but also bound CD1a2, CD1a8, and CD1a9. Interestingly, Ca9.AG5 showed allele specificity based on a single nucleotide polymorphism (SNP) located at position 321. Our...

  18. A survey of canine tick-borne diseases in India

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    Coleman Glen T


    Full Text Available Abstract Background There are few published reports on canine Babesia, Ehrlichia, Anaplasma, Hepatozoon and haemotropic Mycoplasma infections in India and most describe clinical disease in individual dogs, diagnosed by morphological observation of the microorganisms in stained blood smears. This study investigated the occurrence and distribution of canine tick-borne disease (TBD pathogens using a combination of conventional and molecular diagnostic techniques in four cities in India. Results On microscopy examination, only Hepatozoon gamonts were observed in twelve out of 525 (2.3%; 95% CI: 1.2, 4 blood smears. Using polymerase chain reaction (PCR, a total of 261 from 525 dogs (49.7%; 95% CI: 45.4, 54.1 in this study were infected with one or more canine tick-borne pathogen. Hepatozoon canis (30%; 95% CI: 26.0, 34.0 was the most common TBD pathogen found infecting dogs in India followed by Ehrlichia canis (20.6%; 95% CI: 17.2, 24.3, Mycoplasma haemocanis (12.2%; 95% CI: 9.5, 15.3, Anaplasma platys (6.5%; 95% CI: 4.5, 8.9, Babesia vogeli (5.5%, 95% CI: 3.7, 7.8 and Babesia gibsoni (0.2%, 95% CI: 0.01, 1.06. Concurrent infection with more than one TBD pathogen occurred in 39% of cases. Potential tick vectors, Rhipicephalus (most commonly and/or Haemaphysalis ticks were found on 278 (53% of dogs examined. Conclusions At least 6 species of canine tick-borne pathogens are present in India. Hepatozoon canis was the most common pathogen and ticks belonging to the genus Rhipicephalus were encountered most frequently. Polymerase chain reaction was more sensitive in detecting circulating pathogens compared with peripheral blood smear examination. As co-infections with canine TBD pathogens were common, Indian veterinary practitioners should be cognisant that the discovery of one such pathogen raises the potential for multiple infections which may warrant different clinical management strategies.

  19. Genotypic characterization of canine coronaviruses associated with fatal canine neonatal enteritis in the United States. (United States)

    Licitra, Beth N; Whittaker, Gary R; Dubovi, Edward J; Duhamel, Gerald E


    Emerging canine coronavirus (CCoV) variants that are associated with systemic infections have been reported in the European Union; however, CCoV-associated disease in the United States is incompletely characterized. The purpose of this study was to correlate the clinicopathological findings and viral antigen distribution with the genotypic characteristics of CCoV in 11 puppies from nine premises in five states that were submitted for diagnostic investigation at Cornell University between 2008 and 2013. CCoV antigen was found in epithelial cells of small intestinal villi in all puppies and the colon in 2 of the 10 puppies where colon specimens were available. No evidence of systemic CCoV infection was found. Comparative sequence analyses of viral RNA extracted from intestinal tissues revealed CCoV-II genotype in 9 out of 11 puppies. Of the nine CCoV-IIs, five were subtyped as group IIa and one as IIb, while three CCoVs could not be subtyped. One of the CCoV-IIa variants was isolated in cell culture. Infection with CCoV alone was found in five puppies, of which two also had small intestinal intussusception. Concurrent infections with either parvovirus (n = 1), attaching-effacing Escherichia coli (n = 4), or protozoan parasites (n = 3) were found in the other six puppies. CCoV is an important differential diagnosis in outbreaks of severe enterocolitis among puppies between 4 days and 21 weeks of age that are housed at high population density. These findings will assist with the rapid laboratory diagnosis of enteritis in puppies and highlight the need for continued surveillance for CCoV variants and intestinal viral diseases of global significance.

  20. Evaluation of the biological differences of canine and human factor VIII in gene delivery: Implications in human hemophilia treatment (United States)

    The canine is the most important large animal model for testing novel hemophilia A(HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, the different biological properties between cFVIII and human FVII...

  1. Tratamento da papilomatose canina com Propionibacterium acnes Treatment of canine papillomatosis using Propionibacterium acnes

    Directory of Open Access Journals (Sweden)

    J. Megid


    Full Text Available Propionibacterium acnes as immunostimulant in oral canine papillomatosis treatment in 16 animals was studied. Regression of the pappiloma started being observed after the second aplication, with complete resolution in all dogs after the sixth aplication. These results suggest the use of P. acnes as an alternative in oral canine papillomatosis therapy.

  2. Promoter mutation and reduced expression of BRCA1 in canine mammary tumors. (United States)

    Qiu, H B; Sun, W D; Yang, X; Jiang, Q Y; Chen, S; Lin, D G


    Breast cancer 1, early onset (BRCA1) is one of the most important genes in human familial breast cancer, which also plays an important role in canine mammary tumors. The objectives of this study were to determine the promoter sequence of canine BRCA1, to investigate its promoter mutation status and to describe BRCA1 expression pattern in canine mammary tumors. The promoter sequence of canine BRCA1 was acquired by aligning human BRCA1 promoter sequence with canine genomic sequence and confirmed by standard promoter activity analysis. Same as human BRCA1 promoter, the CAAT box and G/C box were found in canine BRCA1 promoter. In order to explore the mutation status of the promoter region and to investigate the expression pattern of this gene, 10 normal canine mammary tissues, 15 benign mammary tumors and 15 malignant mammary tumors were used. By sequencing, 46.7% of the malignant mammary tumors were found with a deletion of one cytosine in the promoter region. The mRNA expression of BRCA1 was significantly reduced in benign and malignant mammary tumors (Ppromoter sequence and to describe the promoter mutation status in canine mammary tumors.

  3. The avian-origin H3N2 canine influenza virus has limited replication in swine (United States)

    A genetically and antigenically distinct H3N2 canine influenza of avian-origin was detected in March of 2015 in Chicago, Illinois. A subsequent outbreak was reported with over 1,000 dogs in the Midwest affected. The potential for canine-to-swine transmission was unknown. Experimental infection in pi...


    NARCIS (Netherlands)



    A canine model is described to study the tolerance of the pancreas to intra-operative radiotherapy (IORT). The canine pancreas is a horseshoe-shaped organ. To create a homogeneous delivery of IORT to the whole pancreas surgical manipulation is necessary which may induce pancreatitis. A resection of

  5. The Establishment of the Pfizer-Canine Comparative Oncology and Genomics Consortium Biospecimen Repository

    Directory of Open Access Journals (Sweden)

    Christina Mazcko


    Full Text Available The Canine Comparative Oncology and Genomics Consortium (CCOGC was formed in 2004 in an effort to capitalize on the generation of a domestic dog genome sequence assembly [1], which created new opportunities to investigate canine cancers at the molecular level [2]. [...

  6. Frequent alteration of the tumor suppressor gene APC in sporadic canine colorectal tumors. (United States)

    Youmans, Lydia; Taylor, Cynthia; Shin, Edwin; Harrell, Adrienne; Ellis, Angela E; Séguin, Bernard; Ji, Xinglai; Zhao, Shaying


    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.

  7. Effect of high contents of dietary animal-derived protein or carbohydrates on canine fecal microbiota

    NARCIS (Netherlands)

    Hang, I.; Rinttila, T.; Zentek, J.; Kettunen, A.; Alaja, S.; Apajalahti, J.A.; Harmoinen, J.; Vos, de W.M.; Spillmann, T.


    BACKGROUND: Considerable evidence suggests that food impacts both the gastro-intestinal (GI) function and the microbial ecology of the canine GI tract. The aim of this study was to evaluate the influence of high-carbohydrate (HC), high-protein (HP) and dry commercial (DC) diets on the canine colonic

  8. Synergistic Effect of Combination Topotecan and Chronomodulated Radiation Therapy on Xenografted Human Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, YanLing; Chen, Xin; Ren, PeiRong; Su, Zhou; Cao, HongYing; Zhou, Jie; Zou, XiaoYan; Fu, ShaoZhi; Lin, Sheng; Fan, Juan; Yang, Bo; Sun, XiaoYang [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Zhou, Yan; Chen, Yue [Department of Medical Imaging, Luzhou Medical College, Luzhou (China); Yang, LingLin, E-mail: [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Wu, JingBo, E-mail: [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China)


    Purpose: To investigate the in vivo chronomodulated radiosensitizing effect of topotecan (TPT) on human nasopharyngeal carcinoma (NPC) and its possible mechanisms. Methods and Materials: Xenografted BALB/c (nu/nu) NPC mice were synchronized with an alternation of 12 hours of light from 0 to 12 hours after light onset (HALO) and 12 hours of darkness to establish a unified biological rhythm. Chronomodulated radiosensitization of TPT was investigated by analysis of tumor regrowth delay (TGD), pimonidazole hydrochloride, histone H2AX phosphorylation, (γ-H2AX) topoisomerase I (Top I), cell cycle, and apoptosis after treatment with (1) TPT (10 mg/kg) alone; (2) radiation therapy alone (RT); and (3) TPT+RT at 3, 9, 15, and 21 HALO. The tumor-loaded mice without any treatment were used as controls. Results: The TPT+RT combination was more effective than TPT or RT as single agents. The TPT+RT combination at 15 HALO was best (TGD = 58.0 ± 3.6 days), and TPT+RT at 3 HALO was worst (TGD = 35.0 ± 1.5 days) among the 4 TPT+RT groups (P<.05). Immunohistochemistry analysis revealed a significantly increased histone H2AX phosphorylation expression and decreased pimonidazole hydrochloride expression in the TPT+RT group at the same time point. The results suggested that the level of tumor hypoxia and DNA damage varied in a time-dependent manner. The expression of Top I in the TPT+RT group was also significantly different from the control tumors at 15 HALO (P<.05). Cell apoptosis index was increased and the proportion of cells in S phase was decreased (P<.05) with the highest value in 15 HALO and the lowest in 3 HALO. Conclusions: This study suggested that TPT combined with chronoradiotherapy could enhance the radiosensitivity of xenografted NPC. The TPT+RT group at 15 HALO had the best therapeutic effect. The chronomodulated radiosensitization mechanisms of TPT might be related to circadian rhythm of tumor hypoxia, cell cycle redistribution, DNA damage, and expression of Top I.

  9. Isolation and characterization of renal cancer stem cells from patient-derived xenografts (United States)

    Azzi, Sandy; Gallerne, Cindy; Michel, Julien Giron; Chiabotto, Giulia; Lecoz, Vincent; Romei, Cristina; Spaggiari, Grazia Maria; Pezzolo, Annalisa; Pistoia, Vito; Angevin, Eric; Gad, Sophie; Ferlicot, Sophie; Messai, Yosra; Kieda, Claudine; Clay, Denis; Sabatini, Federica; Escudier, Bernard; Camussi, Giovanni; Eid, Pierre; Azzarone, Bruno; Chouaib, Salem


    As rapidly developing patient-derived xenografts (PDX) could represent potential sources of cancer stem cells (CSC), we selected and characterized non-cultured PDX cell suspensions from four different renal carcinomas (RCC). Only the cell suspensions from the serial xenografts (PDX-1 and PDX-2) of an undifferentiated RCC (RCC-41) adapted to the selective CSC medium. The cell suspension derived from the original tumor specimen (RCC-41-P-0) did not adapt to the selective medium and strongly expressed CSC-like markers (CD133 and CD105) together with the non-CSC tumor marker E-cadherin. In comparison, PDX-1 and PDX-2 cells exhibited evolution in their phenotype since PDX-1 cells were CD133high/CD105-/Ecadlow and PDX-2 cells were CD133low/CD105-/Ecad-. Both PDX subsets expressed additional stem cell markers (CD146/CD29/OCT4/NANOG/Nestin) but still contained non-CSC tumor cells. Therefore, using different cell sorting strategies, we characterized 3 different putative CSC subsets (RCC-41-PDX-1/CD132+, RCC-41-PDX-2/CD133-/EpCAMlow and RCC-41-PDX-2/CD133+/EpCAMbright). In addition, transcriptomic analysis showed that RCC-41-PDX-2/CD133− over-expressed the pluripotency gene ERBB4, while RCC-41-PDX-2/CD133+ over-expressed several tumor suppressor genes. These three CSC subsets displayed ALDH activity, formed serial spheroids and developed serial tumors in SCID mice, although RCC-41-PDX-1/CD132+ and RCC-41-PDX-2/CD133+ displayed less efficiently the above CSC properties. RCC-41-PDX-1/CD132+ tumors showed vessels of human origin with CSC displaying peri-vascular distribution. By contrast, RCC-41-PDX-2 originated tumors exhibiting only vessels of mouse origin without CSC peri-vascular distribution. Altogether, our results indicate that PDX murine microenvironment promotes a continuous redesign of CSC phenotype, unmasking CSC subsets potentially present in a single RCC or generating ex novo different CSC-like subsets. PMID:26551931

  10. Antiviral effect of lithium chloride on infection of cells by canine parvovirus. (United States)

    Zhou, Pei; Fu, Xinliang; Yan, Zhongshan; Fang, Bo; Huang, San; Fu, Cheng; Hong, Malin; Li, Shoujun


    Canine parvovirus type 2 causes significant viral disease in dogs, with high morbidity, high infectivity, and high mortality. Lithium chloride is a potential antiviral drug for viruses. We determined the antiviral effect of Lithium Chloride on canine parvovirus type 2 in feline kidney cells. The viral DNA and proteins of canine parvovirus were suppressed in a dose-dependent manner by lithium chloride. Further investigation verified that viral entry into cells was inhibited in a dose-dependent manner by lithium chloride. These results indicated that lithium chloride could be a potential antiviral drug for curing dogs with canine parvovirus infection. The specific steps of canine parvovirus entry into cells that are affected by lithium chloride and its antiviral effect in vivo should be explored in future studies.

  11. Alignment of palatally impacted canine with open window technique and modified K-9 spring

    Directory of Open Access Journals (Sweden)

    Dipti Shastri


    Full Text Available The patient was an 18-year-old female who had an Angle Class I malocclusion with a left palatally impacted maxillary canine. The orthodontic treatment of a palatally impacted canine is aimed at bringing the tooth into its correct position in the dental arch without causing any periodontal damage. To achieve this goal, a variety of surgical and orthodontic techniques have been proposed in relation to the position of the impacted tooth and there are various treatment methods used for traction. The duration of the traction was 3 months and alignment duration was 12 months the total treatment time was 15 months. In the following case, we presented that maxillary palatally impacted canine was brought into the arch with open window method for canine exposure and modified K-9 spring for traction, that is simple spring for orthodontic traction of the palatally impacted canines.

  12. Sex determination using mesiodistal dimension of permanent maxillary incisors and canines

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    Rajbir Kaur Khangura


    Full Text Available Background: Sexual dimorphism refers to the differences in size, shape, etc., between males and females. The dentition′s use in sex assessment has been explored and advocated owing to its strength and resistance to peri- and post-mortem insults. Objectives: The study evaluated permanent maxillary incisors and canines for sexual dimorphism and estimated the level of accuracy with which they could be used for sex determination. Materials and Methods: The study was conducted on 100 subjects (50 males, 50 females. The mesiodistal dimension of permanent maxillary incisors and canines was measured and the data were subjected to statistical analysis. Result: Univariate analysis revealed that all permanent maxillary incisors and canines exhibited larger mean values of mesiodistal dimension in males compared to females but only canines were found to be statistically significant for sexual dimorphism. Conclusion: The study showed maxillary canines exhibiting significant sexual dimorphism and can be used for sex determination along with other procedures.

  13. A re-evaluation of subspecific variation and canine dimorphism in woolly spider monkeys (Brachyteles arachnoides). (United States)

    Leigh, S R; Jungers, W L


    A recent study suggests that differing populations of woolly spider monkeys exhibit a substantial degree of morphological, cytogenetic, and behavioral variation. We re-evaluate the differences between populations in the degree of canine tooth height sexual dimorphism and in the frequency of thumbs. Statistical analysis of variation in the degree of canine sexual dimorphism between these populations fails to provide strong evidence for subspecific variation: differences in the degree of canine dimorphism cannot be considered statistically significant. Differences between populations in the frequency of thumbs are, however, statistically significant. The lack of clear distinctions between populations in the degree of canine dimorphism complicates assessments of behavioral variation between these populations. We suggest that the level of geographic variation in woolly spider monkey canine dimorphism is not consistent with subspecific status.

  14. Multispecialty team management of a case with impacted maxillary permanent canines. (United States)

    Tang, E L


    A fifteen-year-old Chinese girl presented with unerupted maxillary permanent canines impacted against the roots of the central incisors, causing malalignment of the maxillary incisors. The canines were fully formed and their apices closed. The potential path of eruption of the canines contraindicated surgical exposure, followed by orthodontic traction. It was decided to transplant the impacted canines to their normal positions, and then align the maxillary anterior teeth, using a fixed orthodontic appliance. The transplantations and the orthodontic treatment were successful, and neither transplant showed signs of root resorption, periodontal pockets, mobility, or pain, three years after surgery. Root canal therapy was performed on the canines after transplantation, because their apices were closed. They were stained by the amalgam in the access cavities, but both responded well to nonvital bleaching using 30 percent H2O2.

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

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    Patil Sandeep S


    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.

  16. Residual Disease in a Novel Xenograft Model of RUNX1-Mutated, Cytogenetically Normal Acute Myeloid Leukemia.

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    Umayal Sivagnanalingam

    Full Text Available Cytogenetically normal acute myeloid leukemia (CN-AML patients harboring RUNX1 mutations have a dismal prognosis with anthracycline/cytarabine-based chemotherapy. We aimed to develop an in vivo model of RUNX1-mutated, CN-AML in which the nature of residual disease in this molecular disease subset could be explored. We utilized a well-characterized patient-derived, RUNX1-mutated CN-AML line (CG-SH. Tail vein injection of CG-SH into NOD scid gamma mice led to leukemic engraftment in the bone marrow, spleen, and peripheral blood within 6 weeks. Treatment of leukemic mice with anthracycline/cytarabine-based chemotherapy resulted in clearance of disease from the spleen and peripheral blood, but persistence of disease in the bone marrow as assessed by flow cytometry and secondary transplantation. Whole exome sequencing of CG-SH revealed mutations in ASXL1, CEBPA, GATA2, and SETBP1, not previously reported. We conclude that CG-SH xenografts are a robust, reproducible in vivo model of CN-AML in which to explore mechanisms of chemotherapy resistance and novel therapeutic approaches.

  17. Safety and efficacy of quadrapeutics versus chemoradiation in head and neck carcinoma xenograft model. (United States)

    Lukianova-Hleb, Ekaterina Y; Kim, Yoo-Shin; Aryasomayajula, Bhawani; Boulikas, Teni; Phan, Jack; Hung, Mien-Chie; Torchilin, Vladimir P; O'Neill, Brian E; Lapotko, Dmitri O


    Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often lacks safety and efficacy. We compared our recently developed cell-level combination approach, quadrapeutics, to chemoradiation therapy to establish pre-clinical data for its biodistribution, safety and efficacy in head and neck squamous cell carcinoma (HNSCC), as a clinically challenging aggressive and resistant cancer. In vitro and in vivo models of four carcinomas were treated with standard chemoradiation and quadrapeutics using identical drug and radiation doses. We applied liposomal cisplatin or doxorubicin, colloidal gold, near-infrared laser pulses and radiation, all at low safe doses. The final evaluation used a xenograft model of HNSCC. Quadrapeutics enhanced standard chemoradiation in vitro by reducing head and neck cancer cell proliferation by 1000-fold, inhibiting tumor growth in vivo by 34-fold and improving animal survival by 5-fold, and reducing the side effects to a negligible level. In quadrapeutics, we observed an "inversion" of the drug efficacy of two standard drugs: doxorubicin, a low efficacy drug for the cancers studied, was two times more efficient than cisplatin, the first choice drug in clinic for HNSCC. The radical therapeutic gain of quadrapeutics resulted from the intracellular synergy of the four components employed which we administered in a specific sequence, while the reduction in the toxicity was due to the low doses of all four components. The biodistribution, safety and efficacy data for quadrapeutics in HNSCC ensure its high translational potential and justify the possibility of clinical trials.

  18. [Chemo- and endocrino-therapy of breast carcinoma xenografts in the dormant or exponential growth phase]. (United States)

    Takeuchi, T


    In case of concerning about recurrence case after operative treatment of breast cancer, we must suppose existence of dormant breast cancer cell. To elucidate a rational treatment of the breast cancer in the dormant stage, we have developed a new treatment model using human breast carcinoma xenografts (MCF-7, R-27 and Br-10) in nude mice. After the sc inoculation of the tumors, the treatment was initiated with or without the previous estradiol (E2) stimulation. While MCF-7 was sensitive to mitomycin C (6 mg/kg i.p.) and and tamoxifen pellet (2.5 mg/mouse s.c.) in the dormant and exponential growth phase, R-27 and Br-10 were sensitive to the drugs only in the exponential growth phase but not in the dormant stage. These results suggested that the sensitivity of human breast carcinoma cells in the dormant stage is rather low, however some strain would be also sensitive to the treatment. This model seems to be useful in evaluating the adjuvant therapy of breast carcinoma after surgery.

  19. Patient-derived tumor xenograft strategies for informed management of patients with metastatic melanoma. (United States)

    Qassemyar, Ahmad; Gabert, Pierre-Elliott; Kluza, Jerome; Duquennoy-Martinot, Véronique; Mortier, Laurent; Marchetti, Philippe; Guerreschi, Pierre


    Metastatic melanoma has benefited from immunotherapy and targeted therapy advances. Faced with the inescapable onset of treatment resistance, the choice of a second-line treatment can be guided by a patient-derived tumor xenograft (PDTX). This new approach requires an excellent multidisciplinary collaboration where the surgeon has a key role to play. Each patient included (stage IIIC or IV) presented with subcutaneous melanoma metastasis that could be surgically resected. The surgeon performed orthotopic PDTX on CB17-SCID mice. To validate the model, tumor material was amplified over three successive generations of animals to obtain cohorts compatible with carrying out a study to compare treatment response by targeted therapy (vemurafenib versus controls). Tumors were characterized (histologically and genetically) at all stages of the generations' amplification. Functional imaging by fluorine-18 fluorodeoxyglucose PET scan was performed for the third generation PDTX. Seventeen patients with a mutated BRAF V600E subcutaneous metastasis were included, yielding 257 PDTX. Clinical, histological, and genetic characteristics of the grafted tumors were stable over the three mice generations. The treatment response to vemurafenib was observed for all PDTX. The fluorine-18 fluorodeoxyglucose PET scan evidenced a decreased in glucose uptake in the treated tumors. PDTX models are being widely used in fundamental research and are more compatible with clinical issues. If PDTX are simple and easily reproducible in metastatic melanoma, an organized multidisciplinary platform is essential to implement them. In our experience, surgeons have a key role to play in the cohesion of this new therapeutic approach.

  20. In vivo PET imaging and biodistribution of radiolabeled gold nanoshells in rats with tumor xenografts. (United States)

    Xie, Huan; Wang, Zheng Jim; Bao, Ande; Goins, Beth; Phillips, William T


    Here we report the radiolabeling of gold nanoshells (NSs) for PET imaging in rat tumor model. A conjugation method was developed to attach NSs with the radionuclide, (64)Cu. The resulting conjugates showed good labeling efficiency and stability in PBS and serum. The pharmacokinetics of (64)Cu-NS and the controls ((64)Cu-DOTA and (64)Cu-DOTA-PEG2K) were determined in nude rats with a head and neck squamous cell carcinoma xenograft by radioactive counting. Using PET/CT imaging, we monitored the in vivo distribution of (64)Cu-NS and the controls in the tumor-bearing rats at various time points after their intravenous injection. PET images of the rats showed accumulation of (64)Cu-NSs in the tumors and other organs with significant difference from the controls. The organ biodistribution of rats at 46h post-injection was analyzed by radioactive counting and compared between the (64)Cu-NS and the controls. Different clearance kinetics was indicated. Neutron activation analysis (NAA) of gold concentration was performed to quantify the amount of NSs in major tissues of the dosed rats and the results showed similar distribution. Overall, PET images with (64)Cu had good resolution and therefore can be further applied to guide photothermal treatment of cancer.

  1. BRAFV600E Kinase Domain Duplication Identified in Therapy-Refractory Melanoma Patient-Derived Xenografts

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    Kristel Kemper


    Full Text Available The therapeutic landscape of melanoma is improving rapidly. Targeted inhibitors show promising results, but drug resistance often limits durable clinical responses. There is a need for in vivo systems that allow for mechanistic drug resistance studies and (combinatorial treatment optimization. Therefore, we established a large collection of patient-derived xenografts (PDXs, derived from BRAFV600E, NRASQ61, or BRAFWT/NRASWT melanoma metastases prior to treatment with BRAF inhibitor and after resistance had occurred. Taking advantage of PDXs as a limitless source, we screened tumor lysates for resistance mechanisms. We identified a BRAFV600E protein harboring a kinase domain duplication (BRAFV600E/DK in ∼10% of the cases, both in PDXs and in an independent patient cohort. While BRAFV600E/DK depletion restored sensitivity to BRAF inhibition, a pan-RAF dimerization inhibitor effectively eliminated BRAFV600E/DK-expressing cells. These results illustrate the utility of this PDX platform and warrant clinical validation of BRAF dimerization inhibitors for this group of melanoma patients.

  2. Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease.

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    Martin Fritsch

    Full Text Available Human uterine fibroids, benign tumors derived from the smooth muscle layers of the uterus, impose a major health burden to up to 50% of premenopausal women in their daily life. To improve our understanding of this disease, we developed and characterized a patient-derived xenograft model by subcutaneous transplantation of pieces of human uterine fibroid tissue into three different strains of severe combined immunodeficient mice. Engrafted uterine fibroid tissue preserved the classical morphology with interwoven bundles of smooth muscle cells and an abundant deposition of collagenous matrix, similar to uterine fibroids in situ. The grafts expressed both estrogen receptor 1 and progesterone receptor. Additionally, both receptors were up-regulated by estrogen treatment. Growth of the fibroid grafts was dependent on 17β-estradiol and progesterone supplementation at levels similar to women with the disease and was studied for up to 60 days at maximum. Co-treatment with the antiprogestin mifepristone reduced graft growth (four independent donors, p<0.0001 two-sided t-test, as did treatment with the mTOR inhibitor rapamycin (three independent donors, p<0.0001 two-sided t-test. This in vivo animal model preserves the main histological and functional characteristics of human uterine fibroids, is amenable to intervention by pharmacological treatment, and can thus serve as an adequate model for the development of novel therapies.

  3. A novel synthetic smoothened antagonist transiently inhibits pancreatic adenocarcinoma xenografts in a mouse model.

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    Martin F Strand

    Full Text Available BACKGROUND: Hedgehog (Hh signaling is over-activated in several solid tumors where it plays a central role in cell growth, stroma recruitment and tumor progression. In the Hh signaling pathway, the Smoothened (SMO receptor comprises a primary drug target with experimental small molecule SMO antagonists currently being evaluated in clinical trials. PRINCIPAL FINDINGS: Using Shh-Light II (Shh-L2 and alkaline phosphatase (AP based screening formats on a "focused diversity" library we identified a novel small molecule inhibitor of the Hh pathway, MS-0022 (2-bromo-N-(4-(8-methylimidazo[1,2-a]pyridin-2-ylphenylbenzamide. MS-0022 showed effective Hh signaling pathway inhibition at the level of SMO in the low nM range, and Hh pathway inhibition downstream of Suppressor of fused (SUFU in the low µM range. MS-0022 reduced growth in the tumor cell lines PANC-1, SUIT-2, PC-3 and FEMX in vitro. MS-0022 treatment led to a transient delay of tumor growth that correlated with a reduction of stromal Gli1 levels in SUIT-2 xenografts in vivo. SIGNIFICANCE: We document the in vitro and in vivo efficacy and bioavailability of a novel small molecule SMO antagonist, MS-0022. Although MS-0022 primarily interferes with Hh signaling at the level of SMO, it also has a downstream inhibitory effect and leads to a stronger reduction of growth in several tumor cell lines when compared to related SMO antagonists.

  4. A Patient-Derived Xenograft Model of Parameningeal Embryonal Rhabdomyosarcoma for Preclinical Studies

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    Jody E. Hooper


    Full Text Available Embryonal rhabdomyosarcoma (eRMS is one of the most common soft tissue sarcomas in children and adolescents. Parameningeal eRMS is a variant that is often more difficult to treat than eRMS occurring at other sites. A 14-year-old female with persistent headaches and rapid weight loss was diagnosed with parameningeal eRMS. She progressed and died despite chemotherapy with vincristine, actinomycin-D, and cyclophosphamide plus 50.4 Gy radiation therapy to the primary tumor site. Tumor specimens were acquired by rapid autopsy and tumor tissue was transplanted into immunodeficient mice to create a patient-derived xenograft (PDX animal model. As autopsy specimens had an ALK R1181C mutation, PDX tumor bearing animals were treated with the pan-kinase inhibitor lestaurtinib but demonstrated no decrease in tumor growth, suggesting that single agent kinase inhibitor therapy may be insufficient in similar cases. This unique parameningeal eRMS PDX model is publicly available for preclinical study.

  5. Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

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    Yingjen Jeffrey Wu


    Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

  6. Vascular Differences Detected by MRI for Metastatic Versus Nonmetastatic Breast and Prostate Cancer Xenografts

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    Zaver M. Bhujwalla


    Full Text Available Several studies have linked vascular density, identified in histologic sections, to “metastatic risk.” Functional information of the vasculature, not readily available from histologic sections, can be obtained with contrast-enhanced MRI to exploit for therapy or metastasis prevention. Our aims were to determine if human breast and prostate cancer xenograffs preselected for differences in invasive and metastatic characteristics established correspondingly different vascular volume and permeability, quantified here with noninvasive MRI of the intravascular contrast agent albumin-GdDTPA. Tumor vascular volume and permeability of human breast and prostate cancer xenografts were characterized using MRI. Parallel studies confirmed the invasive behavior of these cell lines. Vascular endothelial growth factor (VEGF expression in the cell lines was measured using ELISA and Western blots. Metastasis to the lungs was evaluated with spontaneous as well as experimental assay. Metastatic tumors formed vasculature with significantly higher permeability or vascular volume (P < .05, two-sided unpaired t test. The permeability profile matched VEGF expression. Within tumors, regions of high vascular volume usually exhibited low permeability whereas regions of low vascular volume exhibited high permeability. We observed that although invasion was necessary, without adequate vascularization it was not sufficient for metastasis to occur.

  7. Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts

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    Dietmar Abraham


    Full Text Available The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF. PlGF is a member of the vascular endothelial growth factor (VEGF family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.

  8. Neuroblastoma patient-derived orthotopic xenografts retain metastatic patterns and geno- and phenotypes of patient tumours. (United States)

    Braekeveldt, Noémie; Wigerup, Caroline; Gisselsson, David; Mohlin, Sofie; Merselius, My; Beckman, Siv; Jonson, Tord; Börjesson, Anna; Backman, Torbjörn; Tadeo, Irene; Berbegall, Ana P; Ora, Ingrid; Navarro, Samuel; Noguera, Rosa; Påhlman, Sven; Bexell, Daniel


    Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers neural cell adhesion molecule, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high-risk neuroblastoma in patients. PDX-derived cells were cultured in serum-free medium where they formed free-floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour-initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK-N-BE(2)c cell line-derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high-risk metastatic neuroblastoma.

  9. Cellular characterization of ultrasound-stimulated microbubble radiation enhancement in a prostate cancer xenograft model

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    Azza A. Al-Mahrouki


    Full Text Available Tumor radiation resistance poses a major obstacle in achieving an optimal outcome in radiation therapy. In the current study, we characterize a novel therapeutic approach that combines ultrasound-driven microbubbles with radiation to increase treatment responses in a prostate cancer xenograft model in mice. Tumor response to ultrasound-driven microbubbles and radiation was assessed 24 hours after treatment, which consisted of radiation treatments alone (2 Gy or 8 Gy or ultrasound-stimulated microbubbles only, or a combination of radiation and ultrasound-stimulated microbubbles. Immunohistochemical analysis using in situ end labeling (ISEL and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL revealed increased cell death within tumors exposed to combined treatments compared with untreated tumors or tumors exposed to radiation alone. Several biomarkers were investigated to evaluate cell proliferation (Ki67, blood leakage (factor VIII, angiogenesis (cluster of differentiation molecule CD31, ceramide-formation, angiogenesis signaling [vascular endothelial growth factor (VEGF], oxygen limitation (prolyl hydroxylase PHD2 and DNA damage/repair (γH2AX. Results demonstrated reduced vascularity due to vascular disruption by ultrasound-stimulated microbubbles, increased ceramide production and increased DNA damage of tumor cells, despite decreased tumor oxygenation with significantly less proliferating cells in the combined treatments. This combined approach could be a feasible option as a novel enhancing approach in radiation therapy.

  10. Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours. (United States)

    Braekeveldt, Noémie; Wigerup, Caroline; Tadeo, Irene; Beckman, Siv; Sandén, Caroline; Jönsson, Jimmie; Erjefält, Jonas S; Berbegall, Ana P; Börjesson, Anna; Backman, Torbjörn; Øra, Ingrid; Navarro, Samuel; Noguera, Rosa; Gisselsson, David; Påhlman, Sven; Bexell, Daniel


    Treatment of high-risk childhood neuroblastoma is a clinical challenge which has been hampered by a lack of reliable neuroblastoma mouse models for preclinical drug testing. We have previously established invasive and metastasising patient-derived orthotopic xenografts (PDXs) from high-risk neuroblastomas that retained the genotypes and phenotypes of patient tumours. Given the important role of the tumour microenvironment in tumour progression, metastasis, and treatment responses, here we analysed the tumour microenvironment of five neuroblastoma PDXs in detail. The PDXs resembled their parent tumours and retained important stromal hallmarks of aggressive lesions including rich blood and lymphatic vascularisation, pericyte coverage, high numbers of cancer-associated fibroblasts, tumour-associated macrophages, and extracellular matrix components. Patient-derived tumour endothelial cells occasionally formed blood vessels in PDXs; however, tumour stroma was, overall, of murine origin. Lymphoid cells and lymphatic endothelial cells were found in athymic nude mice but not in NSG mice; thus, the choice of mouse strain dictates tumour microenvironmental components. The murine tumour microenvironment of orthotopic neuroblastoma PDXs reflects important hallmarks of aggressive and metastatic clinical neuroblastomas. Neuroblastoma PDXs are clinically relevant models for preclinical drug testing.

  11. Inhibition of angiogenesis and HCT-116 xenograft tumor growth in mice by kallistatin

    Institute of Scientific and Technical Information of China (English)

    Yong Diao; Rui-An Xu; Jian Ma; Wei-Dong Xiao; Jia Luo; Xin-Yan Li; Kin-Wah Chu; Peter WC Fung; Nagy Habib; Farzin Farzaneh


    AIM: To investigate the inhibitory effect of kallistatin (KAL) on angiogenesis and HCT-116 xenograft tumor growth.METHODS: Heterotopic tumors were induced by subcutaneous injection of 2 × 106 HCT-11 cells in mice.Seven days later, 2 × 1011 rAAV-GFP or rAAV-KAL was injected intratumorally (n = 5 for each group). The mice were sacrificed at d 28, by which time the tumors in the rAAV-GFP group had grown to beyond 5% of the total body weight. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density (MVD) by immunohistology. Tumor cell proliferation was assessed by Ki-67 staining.RESULTS: Intratumor injection of rAAV-KAL inhibited tumor growth in the treatment group by 78% (171 ±52 mm3) at d 21 after virus infection compared to the control group (776 ± 241 mm3). Microvessel density was significantly inhibited in tumor tissues treated with rAAV-KAL. rAAV-KAL also decreased the proportion of proliferating cells (Ki-67 positive cells) in tumors compared with the control group.CONCLUSION: rAAV-mediated expression of KAL inhibits the growth of colon cancer by reducing angiogenesis and proliferation of tumor cells, and may provide a promising anti-angiogenesis-based approach to the treatment of metastatic colorectal cancer.

  12. Mass Spectrometric Imaging of Red Fluorescent Protein in Breast Tumor Xenografts (United States)

    Chughtai, Kamila; Jiang, Lu; Post, Harm; Winnard, Paul T.; Greenwood, Tiffany R.; Raman, Venu; Bhujwalla, Zaver M.; Heeren, Ron M. A.; Glunde, Kristine


    Mass spectrometric imaging (MSI) in combination with electrospray mass spectrometry (ESI-MS) is a powerful technique for visualization and identification of a variety of different biomolecules directly from thin tissue sections. As commonly used tools for molecular reporting, fluorescent proteins are molecular reporter tools that have enabled the elucidation of a multitude of biological pathways and processes. To combine these two approaches, we have performed targeted MS analysis and MALDI-MSI visualization of a tandem dimer (td)Tomato red fluorescent protein, which was expressed exclusively in the hypoxic regions of a breast tumor xenograft model. For the first time, a fluorescent protein has been visualized by both optical microscopy and MALDI-MSI. Visualization of tdTomato by MALDI-MSI directly from breast tumor tissue sections will allow us to simultaneously detect and subsequently identify novel molecules present in hypoxic regions of the tumor. MS and MALDI-MSI of fluorescent proteins, as exemplified in our study, is useful for studies in which the advantages of MS and MSI will benefit from the combination with molecular approaches that use fluorescent proteins as reporters.

  13. Quantitative proteomic analysis of human lung tumor xenografts treated with the ectopic ATP synthase inhibitor citreoviridin.

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    Yi-Hsuan Wu

    Full Text Available ATP synthase is present on the plasma membrane of several types of cancer cells. Citreoviridin, an ATP synthase inhibitor, selectively suppresses the proliferation and growth of lung cancer without affecting normal cells. However, the global effects of targeting ectopic ATP synthase in vivo have not been well defined. In this study, we performed quantitative proteomic analysis using isobaric tags for relative and absolute quantitation (iTRAQ and provided a comprehensive insight into the complicated regulation by citreoviridin in a lung cancer xenograft model. With high reproducibility of the quantitation, we obtained quantitative proteomic profiling with 2,659 proteins identified. Bioinformatics analysis of the 141 differentially expressed proteins selected by their relative abundance revealed that citreoviridin induces alterations in the expression of glucose metabolism-related enzymes in lung cancer. The up-regulation of enzymes involved in gluconeogenesis and storage of glucose indicated that citreoviridin may reduce the glycolytic intermediates for macromolecule synthesis and inhibit cell proliferation. Using comprehensive proteomics, the results identify metabolic aspects that help explain the antitumorigenic effect of citreoviridin in lung cancer, which may lead to a better understanding of the links between metabolism and tumorigenesis in cancer therapy.

  14. Ultrasound-enhanced drug delivery in prostate cancer xenografts by nanoparticles stabilizing microbubbles. (United States)

    Eggen, Siv; Fagerland, Stein-Martin; Mørch, Ýrr; Hansen, Rune; Søvik, Kishia; Berg, Sigrid; Furu, Håkon; Bøhn, Audun Dybvik; Lilledahl, Magnus B; Angelsen, Anders; Angelsen, Bjørn; de Lange Davies, Catharina


    The delivery of nanoparticles to solid tumors is often ineffective due to the lack of specificity towards tumor tissue, limited transportation of the nanoparticles across the vascular wall and poor penetration through the extracellular matrix of the tumor. Ultrasound is a promising tool that can potentially improve several of the transportation steps, and the interaction between sound waves and microbubbles generates biological effects that can be beneficial for the successful delivery of nanocarriers and their contents. In this study, a novel platform consisting of nanoparticle-stabilized microbubbles has been investigated for its potential for ultrasound-enhanced delivery to tumor xenografts. Confocal laser scanning microscopy was used to study the supply of nanoparticles from the vasculature and to evaluate the effect of different ultrasound parameters at a microscopic level. The results demonstrated that although the delivery is heterogeneous within tumors, there is a significant improvement in the delivery and the microscopic distribution of both nanoparticles and a released model drug when the nanoparticles are combined with microbubbles and ultrasound. The mechanisms that underlie the improved delivery are discussed.

  15. SNCG shRNA suppressed breast cancer cell xenograft formation and growth in nude mice

    Institute of Scientific and Technical Information of China (English)

    SHEN Pei-hong; FAN Qing-xia; LI Yan-wei; ZHANG Wei; HE Xiao-kai; WANG Zhen; ZHANG Yun-han


    Background Overexpression of breast cancer-specific gene 1 (SNCG) is associated with poor prognosis in advanced breast cancer patients. This study aimed to determine the effects of SNCG knockdown in breast cancer cells by using small hairpin RNA (shRNA).Methods Four different SNCG shRNA oligonucleotides were designed and chemically synthesized to construct mammalian expression vectors. These vectors were then stably transfected into a breast cancer MCF-7 cell line to knockdown SNCG expression. After SNCG knockdown was confirmed, the stable cell lines were inoculated into nude mice. SNCG mRNA and protein expressions were analyzed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively in both the stable cell lines and xenografts.Results All four SNCG shRNA constructs significantly reduced SNCG mRNA and protein levels in MCF-7 cells, as compared to the unrelated sequence control shRNA and the liposome control mice (P<0.05). SNCG-knockdown MCF-7cells formed significantly smaller tumor masses than cells expressing the unrelated sequence control or the liposome control mice (P<0.05).Conclusion SNCG shRNA effectively suppressed breast cancer cell formation in vivo and may be a useful clinical strategy to control breast cancer.

  16. Expression of cell cycle regulating factor mRNA in small cell lung cancer xenografts

    DEFF Research Database (Denmark)

    Krarup, M; Poulsen, H S; Spang-Thomsen, M


    We have investigated the expression of cyclins, cyclin dependent kinases (CDK), and CDK inhibitors (CKI) at the mRNA level in a panel of small-cell lung cancer (SCLC) cell lines in vitro and in vivo as xenografts in nude mice. The results showed that the cell lines expressed varying amounts of most...... cyclin and CDK's but only a few of the cell lines expressed cyclin D1 and/or D2 and some lacked expression of CDK6. Most cell lines expressed mRNA for the CKI's but two cell lines lacked expression of P15INK4B and p16INK4A. The mRNA expression differed for a few of the cell lines regarding cyclin D2...... and CDK6 when in vitro and in vivo data were compared. Two of the cell lines that express the retinoblastoma (Rb) protein had no sign of a deregulated Rb pathway but further studies at the protein level are necessary to demonstrate whether these two cell lines should have a normal Rb pathway or whether...

  17. Low toxicity and anticancer activity of a novel liposomal cisplatin (Lipoplatin) in mouse xenografts. (United States)

    Boulikas, Teni


    Cisplatin has been one of the most widely used and most effective cytotoxic agents in the treatment of malignancies but causes severe adverse reactions including nausea/vomiting, renal toxicity, gastrointestinal toxicity, peripheral neuropathy, asthenia, and ototoxicity. A liposomal formulation of cisplatin, Lipoplatin, was developed in order to reduce the systemic toxicity of cisplatin. A single treatment of rats with 30 mg/kg Lipoplatin resulted in no toxicity whereas 2 or 3 weekly administrations at 30 mg/kg to rats gave neutropenia but no nephrotoxicity. On the contrary, a single injection to rats of 5 mg/kg cisplatin resulted in severe nephrotoxicity. Thus, Lipoplatin is less toxic than cisplatin in rats. Intraperitoneal or intravenous injection of Lipoplatin to SCID (severe combined immunodeficient) mice with subcutaneous breast MCF-7 or prostate LNCaP human tumors resulted in size reduction of the tumors; histological examination of the treated tumors in xenografts was consistent with apoptosis in tumor cells; thus, Lipoplatin appears to exert its cytotoxic effects to tumors in a mechanism similar to that of cisplatin. The preclinical studies reported here set the foundation for the clinical use of Lipoplatin as an exciting new drug with lower toxicity than cisplatin, endowed with proapoptotic properties.

  18. Expression of myc family oncoproteins in small-cell lung-cancer cell lines and xenografts

    DEFF Research Database (Denmark)

    Rygaard, K; Vindeløv, L L; Spang-Thomsen, M


    A number of genes have altered activity in small-cell lung cancer (SCLC), but especially genes of the myc family (c-myc, L-myc and N-myc) are expressed at high levels in SCLC. Most studies have explored expression at the mRNA level, whereas studies of myc family oncoprotein expression are sparse....... WE examined the expression of myc proto-oncogenes at the mRNA and protein level in 23 cell lines or xenografts. In the cell lines, the doubling time and the cell-cycle distribution, as determined by flow-cytometric DNA analysis, were examined to establish whether the level of myc-gene-family...... expression correlated with proliferative parameters. All tumours expressed at least one myc family member at the mRNA level. Exclusive c-myc mRNA expression was demonstrated in 8 tumours, L-myc in 7 and N-myc in I. Five tumours expressed both c-myc and L-myc, and 2 tumours expressed both c-myc and N...

  19. Moxifloxacin increases anti-tumor and anti-angiogenic activity of irinotecan in human xenograft tumors. (United States)

    Reuveni, Debby; Halperin, Drora; Fabian, Ina; Tsarfaty, Galia; Askenasy, Nadir; Shalit, Itamar


    Camptothecins (CPTs) are topoisomerase I inhibitors chemotherapeutic agents used in combination chemotherapy. We showed previously that combination of moxifloxacin (MXF) and CPT induced inhibitory effects on topoisomerase I activity, on proliferation of HT-29 cells in vitro and enhanced apoptosis, compared to CPT alone. Analysis of secretion of the pro-angiogenic factors IL-8 and VEGF showed significant reduction by MXF. Using a murine model of human colon carcinoma xenograft, we compared the effects of MXF/CPT in vitro to MXF/irinotecan combination in vivo. We show that the MXF/CPT inhibitory effects observed in vitro are reflected in the inhibition of the progressive growth of HT-29 cells implanted in SCID mice. Using caliper measurements, Doppler ultrasonography, image analyses and immunohistochemistry of nuclear proteins (Ki-67) and vascular endothelial cells (CD-31) we show that addition of MXF (45mg/kg) to a relatively ineffective dose of irinotecan (20mg/kg), results in a 50% and 30% decrease, respectively, in tumor size and a decrease in Ki-67 staining. Power Doppler Ultrasound showed a significant, pronounced decrease in the number of blood vessels, as did CD-31 staining, indicating decreased blood flow in tumors in mice treated with MXF alone or MXF/irinotecan compared to irinotecan. These results suggest that the combination of MXF/irinotecan may result in enhanced anti-neoplastic/anti-angiogenic activity.

  20. Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac (United States)

    Sudha, Thangirala; Bharali, Dhruba J; Yalcin, Murat; Darwish, Noureldien HE; Debreli Coskun, Melis; Keating, Kelly A; Lin, Hung-Yun; Davis, Paul J; Mousa, Shaker A


    The tetraiodothyroacetic acid (tetrac) component of nano-diamino-tetrac (NDAT) is chemically bonded via a linker to a poly(lactic-co-glycolic acid) nanoparticle that can encapsulate anticancer drugs. Tetrac targets the plasma membrane of cancer cells at a receptor on the extracellular domain of integrin αvβ3. In this study, we evaluate the efficiency of NDAT delivery of paclitaxel and doxorubicin to, respectively, pancreatic and breast cancer orthotopic nude mouse xenografts. Intra-tumoral drug concentrations were 5-fold (paclitaxel; P<0.001) and 2.3-fold (doxorubicin; P<0.01) higher than with conventional systemic drug administration. Tumor volume reductions reflected enhanced xenograft drug uptake. Cell viability was estimated by bioluminescent signaling in pancreatic tumors and confirmed an increased paclitaxel effect with drug delivery by NDAT. NDAT delivery of chemotherapy increases drug delivery to cancers and increases drug efficacy. PMID:28243091

  1. Molecularly Characterised Xenograft Tumour Mouse Models: Valuable Tools for Evaluation of New Therapeutic Strategies for Secondary Liver Cancers

    Directory of Open Access Journals (Sweden)


    Full Text Available To develop and evaluate new therapeutic strategies for the treatment of human cancers, well-characterised preclinical model systems are a prerequisite. To this aim, we have established xenotransplantation mouse models and corresponding cell cultures from surgically obtained secondary human liver tumours. Established xenograft tumours were patho- and immunohistologically characterised, and expression levels of cancer-relevant genes were quantified in paired original and xenograft tumours and the derivative cell cultures applying RT-PCR-based array technology. Most of the characteristic morphological and immunohistochemical features of the original tumours were shown to be maintained. No differences were found concerning expression of genes involved in cell cycle regulation and oncogenesis. Interestingly, cytokine and matrix metalloproteinase encoding genes appeared to be expressed differentially. Thus, the established models are closely reflecting pathohistological and molecular characteristics of the selected human tumours and may therefore provide useful tools for preclinical analyses of new antitumour strategies in vivo.

  2. Manipulation of radiobiological hypoxia in a human melanoma xenograft to exploit the bioreductive cytotoxicity of RSU-1069

    Energy Technology Data Exchange (ETDEWEB)

    Cole, S.; Stratford, I.J.; Adams, G.E. (Medical Research Council, Harwell (UK). Radiobiological Research Unit)


    RSU-1069 (a 2-nitroimidazole) is known to be an efficient hypoxic cell radiosensitizer and potent cytotoxin for hypoxic cells in murine tumours (Chaplin et al. 1986). The authors demonstrated that the compound is also able to kill human melanoma cells, growing as a xenograft, provided the tumour blood supply is occluded for an hour or more, thereby substantially increasing the proportion of susceptible, hypoxic cells. Pharmacokinetic effects may also contribute to this phenomenon, as the effectiveness of bioreductive cytotoxic agents may increase with prolonged contact times (Stratford et al. 1986b). Hydralazine increased radiobiological hypoxia in the HX118 xenograft but this did not enhance the susceptibility of clonogenic melanoma cells to killing by RSU-1069. (author).

  3. Tumour bed irradiation of human tumour xenografts in a nude rat model using a common X-ray tube

    Indian Academy of Sciences (India)

    S V Tokalov; W Enghardt; N Abolmaali


    Studies that investigate the radiation of human tumour xenografts require an appropriate radiation source and highly standardized conditions during radiation. This work reports on the design of a standardized irradiation device using a commercially available X-ray tube with a custom constructed lead collimator with two circular apertures and an animal bed plate, permitting synchronous irradiation of two animals. Dosimetry and the corresponding methodology for radiotherapy of human non-small cell lung cancer xenograft tumours transplanted to and growing subcutaneously on the right lower limb in a nude rat model were investigated. Procedures and results described herein prove the feasibility of use of the device, which is applicable for any investigation involving irradiation of non-tumorous and tumorous lesions in small animals.

  4. The Public Repository of Xenografts (ProXe) enables discovery and randomized phase II-like trials in mice (United States)

    Townsend, Elizabeth C.; Murakami, Mark A.; Christodoulou, Alexandra; Christie, Amanda L.; Köster, Johannes; DeSouza, Tiffany A.; Morgan, Elizabeth A.; Kallgren, Scott P.; Liu, Huiyun; Wu, Shuo-Chieh; Plana, Olivia; Montero, Joan; Stevenson, Kristen E.; Rao, Prakash; Vadhi, Raga; Andreeff, Michael; Armand, Philippe; Ballen, Karen K.; Barzaghi-Rinaudo, Patrizia; Cahill, Sarah; Clark, Rachael A.; Cooke, Vesselina G.; Davids, Matthew S.; DeAngelo, Daniel J.; Dorfman, David M.; Eaton, Hilary; Ebert, Benjamin L.; Etchin, Julia; Firestone, Brant; Fisher, David C.; Freedman, Arnold S.; Galinsky, Ilene A.; Gao, Hui; Garcia, Jacqueline S.; Garnache-Ottou, Francine; Graubert, Timothy A.; Gutierrez, Alejandro; Halilovic, Ensar; Harris, Marian H.; Herbert, Zachary T.; Horwitz, Steven M.; Inghirami, Giorgio; Intlekoffer, Andrew M.; Ito, Moriko; Izraeli, Shai; Jacobsen, Eric D.; Jacobson, Caron A.; Jeay, Sébastien; Jeremias, Irmela; Kelliher, Michelle A.; Koch, Raphael; Konopleva, Marina; Kopp, Nadja; Kornblau, Steven M.; Kung, Andrew L.; Kupper, Thomas S.; LaBoeuf, Nicole; LaCasce, Ann S.; Lees, Emma; Li, Loretta S.; Look, A. Thomas; Murakami, Masato; Muschen, Markus; Neuberg, Donna; Ng, Samuel Y.; Odejide, Oreofe O.; Orkin, Stuart H.; Paquette, Rachel R.; Place, Andrew E.; Roderick, Justine E.; Ryan, Jeremy A.; Sallan, Stephen E.; Shoji, Brent; Silverman, Lewis B.; Soiffer, Robert J.; Steensma, David P.; Stegmaier, Kimberly; Stone, Richard M.; Tamburini, Jerome; Thorner, Aaron R.; van Hummelen, Paul; Wadleigh, Martha; Wiesmann, Marion; Weng, Andrew P.; Wuerthner, Jens U.; Williams, David A.; Wollison, Bruce M.; Lane, Andrew A.; Letai, Anthony; Bertagnolli, Monica M.; Ritz, Jerome; Brown, Myles; Long, Henry; Aster, Jon C.; Shipp, Margaret A.; Griffin, James D.; Weinstock, David M.


    Summary Over 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publically available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment called the Public Repository of Xenografts (PRoXe; PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional and proteomic biomarkers in both treatment-naïve and relapsed/refractory disease. PMID:27070704

  5. Identification of replication-competent HSV-1 Cgal+ strain targets in a mouse model of human hepatocarcinoma xenograft


    Santamaria, E. (Enrique); Mora, M.I.; Carro-Roldan, E. (Elvira); M Molina; Fernandez-Irigoyen, J. (Joaquín); Marconi, P; Manservigi, R; Greco, A.; Epstein, A L; Prieto, J.; Hernandez-Alcoceba, R. (Rubén); Corrales, F. J.


    Recent studies based on animal models have shown the advantages and potential of oncolytic viral therapy using HSV-1 -based replication-competent vectors in the treatment of liver tumors, but little is known about the cellular targets that are modulated during viral infection. In the present work, we have studied the effects of intratumoral injections of HSV-1 Cgal(+) strain in a murine model of human hepatoma xenografts. Viral replication was assessed for more than 1month, leading to a signi...

  6. A novel, diffusely infiltrative xenograft model of human anaplastic oligodendroglioma with mutations in FUBP1, CIC, and IDH1.

    Directory of Open Access Journals (Sweden)

    Barbara Klink

    Full Text Available Oligodendroglioma poses a biological conundrum for malignant adult human gliomas: it is a tumor type that is universally incurable for patients, and yet, only a few of the human tumors have been established as cell populations in vitro or as intracranial xenografts in vivo. Their survival, thus, may emerge only within a specific environmental context. To determine the fate of human oligodendroglioma in an experimental model, we studied the development of an anaplastic tumor after intracranial implantation into enhanced green fluorescent protein (eGFP positive NOD/SCID mice. Remarkably after nearly nine months, the tumor not only engrafted, but it also retained classic histological and genetic features of human oligodendroglioma, in particular cells with a clear cytoplasm, showing an infiltrative growth pattern, and harboring mutations of IDH1 (R132H and of the tumor suppressor genes, FUBP1 and CIC. The xenografts were highly invasive, exhibiting a distinct migration and growth pattern around neurons, especially in the hippocampus, and following white matter tracts of the corpus callosum with tumor cells accumulating around established vasculature. Although tumors exhibited a high growth fraction in vivo, neither cells from the original patient tumor nor the xenograft exhibited significant growth in vitro over a six-month period. This glioma xenograft is the first to display a pure oligodendroglioma histology and expression of R132H. The unexpected property, that the cells fail to grow in vitro even after passage through the mouse, allows us to uniquely investigate the relationship of this oligodendroglioma with the in vivo microenvironment.

  7. Dynamic {sup 18}F-FDG PET for Assessment of Tumor Physiology in Two Breast Carcinoma Xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Kristian, Alexandr; Nilsen, Line B.; Roe, Kathrine; Revheim, Monaelisabeth; Engebraten, Olav; Maelandsmo, Gunhild M.; Holm, Ruth; Malinen Eirik; Seierstad, Therese [Oslo Univ. Hospital, Oslo (Norway)


    To compare dynamic 2-deoxy-2-[{sup 18}F]fluoro-D-glucose positron emission tomography ({sup 18}F-FDG PET) parameters in two selected human breast cancer xenografts and to evaluate associations with immunohistochemistry and histology. Dynamic {sup 18}F-FDG PET of luminal-like MAS98.06 and basal-like MAS98.12 xenografts was performed, and the compartmental transfer rates (k{sub 1}, k{sub 2}, k{sub 3}), blood volume fraction (v{sub B}) and metabolic rate of {sup 18}F-FDG(MR{sub FDG}) were estimated from pharmacokinetic model analysis. After sacrifice, analyses of hypoxia (pimonidazole), proliferation (Ki-67), vascularization (CD31), glucose transport receptor (GLUT1) and necrosis (HE) was performed. The level of hexokinase 2 (HK2) was estimated from Western blot analysis. The {sup 18}F-FDG uptake curves for the two xenografts were significantly different (p<0.05). k{sub 1} and v{sub B} were higher for MAS98.12 (p<0.01), while k{sub 3} was higher for MAS98.06 (p<0.01). MAS98.12 had a higher fraction of stromal tissue and higher microvessel density (MVD), and it was less necrotic and hypoxic than MAS98.06 MAS98.12 had stronger positive GLUT1 staining and lower Ki-67 than MAS98.06. In both models significant correlations were found between k{sub 1} and the GLUT1 score, between k{sub 3} and the level of HK2, and between v{sub B} and MVD. Significant differences in dynamic {sup 18}F-FDG parameters between the two human breast cancer xenografts were found. The differences could be explained by underlying histological and physiological characteristics.

  8. Regulation of estrogen receptors α and β in human breast carcinoma by exogenous leptin in nude mouse xenograft model

    Institute of Scientific and Technical Information of China (English)

    YU Wei; GU Jun-chao; LIU Jian-zhong; WANG Shao-hong; WANG Yu; ZHANG Zhong-tao; MA Xue-mei; SONG Mao-min


    Background It is essential to clarify the interactions of hormones during the progression of human breast cancer. This study examined the effects of exogenous human leptin on estrogen receptor (ER) α and β in human breast tumor tissue in a nude mouse xenograft model.Methods We created nude mice xenografts of MCF-7 human breast cancer cells, and randomly divided them into an experimental group and a control group. The mice in experimental group were injected subcutaneously around tumors with human leptin, while the control group were injected with the same dose of normal saline. A real-time RT-PCR assay was developed to quantify the mRNA of Erα,β in the tumor tissues. Western blotting analyses were used to assess the relative quantities of the Erα,β proteins.Results Leptin-treated xenografted nude mice were successfully established. The amount of Era mRNA was significantly higher in the leptin group than in the control group (P<0.01), while the amount of Erβ mRNA was significantly lower in the leptin group than in the control group (P<0.01). Western blotting analyses revealed that the Erα protein level was significantly higher in the leptin group than in the control group (P<0.01), while the Erβ protein level was significantly lower in the leptin group than in the control group (P <0.01).Conclusions Nude mouse xenograft model can be safely and serviceably treated with human leptin by subcutaneous injections around tumor. Erα,β were both targets of leptin in breast cancer. Leptin can up-regulate the expression of Erα and down-regulate the expression of the Erβ in human breast tumor.

  9. Electrical heterogeneity of canine right ventricular transient outward potassium currents

    Institute of Scientific and Technical Information of China (English)

    杨新春; 周鹏; 李翠兰


    Background Some studies have confirmed that the right ventricular walls of most rodents, such as canines and humans, have evident transient outward potassium current (lto1) heterogeneity, and this heterogeneity is closely related to J point elevation, J wave formation, and some ventricular tachycardias such as ventricular fibrillations caused by Brugada syndrome. This study is designed to investigate transmural electrical heterogeneity of the canine right ventricle during repolarization (phase 1) from the viewpoint of 4-aminopyridine sensitive and calcium-independent lto1.Methods Adult canine single right ventricular epicardial (Epi) cells, mid-myocardial (M) cells, and endocardial (Endo) cells were enzymatically dissociated. Whole cell voltage-clamp recordings were made to compare the lto1 values of the three cell types.Results At 37℃ and using 0.2 Hz and + 70 mV depolarizing test potentials, the average peak lto1 values of Epi cells and M cells averaged (4070±1720) pA and (3540±1840) pA, respectively. The activated and inactivated Epi and M cells kinetic processes were in accordance with the Boltzmann distribution. Compared with lto1 in Epi cells and M cells, the average peak lto1 in Endo cells was very low, averaged (470±130) pA.Conclusions These results suggest that there are evident differences and potent gradients in lto1 between the three cardiac cell types, especially between Epi and Endo cells. These differences are among the prominent manifestations of right ventricular electrical heterogeneity, and may form an important ionic basis and prerequisite for some malignant arrhythmias in the right ventricle, including those arising from Brugada syndrome and other diseases.

  10. Gastrotomy closure using bioabsorbable plugs in a canine model. (United States)

    Cios, Theodore J; Reavis, Kevin M; Renton, David R; Hazey, Jeffrey W; Mikami, Dean J; Narula, Vimal K; Allemang, Matthew T; Davis, S Scott; Melvin, W Scott


    The repair of gastric perforation commonly involves simple suture closure using an open or laparoscopic approach. An endolumenal approach using prosthetic materials may be beneficial. The role of bioprosthetics in this instance has not been thoroughly investigated, thus the authors evaluated the feasibility of gastric perforation repair using a bioabsorbable device and quantified gross and histological changes at the injury site. Twelve canines were anesthetized and underwent open gastrotomy. A 1-cm-diameter perforation was created in the anterior wall of the stomach and plugged with a bioabsorbable device. Intralumenal pH was recorded. Canines were sacrificed at one, four, six, eight, and 12 weeks. The stomach was explanted followed by gross and histological examination. The injury site was examined. The relative ability of the device to seal the perforation was recorded, as were postoperative changes. Tissue samples were analyzed for gross and microscopic tissue growth and compared to normal gastric tissue in the same animal as an internal control. A scoring system of -2 to +2 was used to measure injury site healing (-2= leak, -1= no leak and minimal ingrowth, 0= physiologic healing, +1= mild hypertrophic tissue, +2= severe hypertrophic tissue). In all canines, the bioprosthesis successfully sealed the perforation without leak under ex vivo insufflation. At one week, the device maintained its integrity but there was no tissue ingrowth. Histological healing score was -1. At 4-12 weeks, gross examination revealed a healed injury site in all animals. The lumenal portion of the plug was completely absorbed. The gross and histological healing score ranged from -1 to +1. The application of a bioabsorbable device results in durable closure of gastric perforation with physiologic healing of the injury site. This method of gastrotomy closure may aid in the evolution of advanced endoscopic approaches to perforation closure of hollow viscera.

  11. Changes of Haematobiochemical Parameters during Canine Parvoviral Enteritis

    Directory of Open Access Journals (Sweden)



    Full Text Available Canine parvovirus is a highly contagious virus that can affect all dogs, but unvaccinated dogs and puppies younger than four months old are the most at risk. The pathology caused by CPV-2 is very common in Albania despite the existence of an effective vaccine.Changes in haematobiochemical parameters during canine parvoviral enteritiswould be very important for determining the prognosis of the disease. This hypothesis prompted the start of the study. From fecal samples taken from puppies 65 individuals resulted positive. Of all individuals 14 of them (21.5% failed to survive. All puppies presented leukopenia. In individuals that survived the WBC count began to grow in the first 24- 48 hours (p <0.05. In non-survivors the WBC was never higher than 2.1x109 / l at the time of admission in the clinic and in the first 24-48 hours began to decline further (p <0.05. There weren’t significant change in RBC count (p <0.05. In the first 12-24 hours 54% of individuals who did not survive had a PLT count less than 362.28x109 / l compared to only 8% of individuals who survived. Urea and creatinine were higher in survivors compared to nonsurvivors (p <0.05.These parameters reached normal levels after the start of the treatment in individuals that survived. Urea and creatinine levels in non-survivors continued to decrease until they died. The changes observed in leukocyte, platelet, urea and serum creatinine levels duringfirst stages of canine parvoviral enteritiscan be used to determine prognosis.

  12. Root Canal Morphology of Permanent Maxillary and Mandibular Canines in Indian Population Using Cone Beam Computed Tomography

    Directory of Open Access Journals (Sweden)

    Nikhita Somalinga Amardeep


    Full Text Available Aim. To investigate the root canal anatomy of single-rooted permanent maxillary and mandibular canines in an Indian population using cone beam computed tomography (CBCT. Methodology. A total of 250 permanent maxillary canines and 250 permanent mandibular canines were selected and scanned using CBCT. The root anatomy of each tooth was evaluated for the following parameters: the pattern of the root canals, anatomic length of the crown and the root, the presence of accessory canals, the shape of the access cavity, the position of the apical foramina, root diameter, and dentin thickness of the root. Results. Majority of the teeth had a Type I canal configuration in both maxillary canines (81.6% and mandibular canines (79.6%. In maxillary canine the other canal patterns found were Type III (11.6%, Type II (2.8%, Type V (2%, Type XIX (1.2%, and Type IV (0.8%. In mandibular canines the various other canal patterns found were Type III (13.6%, Type II (3.2%, Type V (2%, and Type XIX (1.6%. Apical foramina were laterally positioned in the majority of the teeth, 70.4% and 65.6% in maxillary and mandibular canines, respectively. 12% of the maxillary canines and 12.8% of the mandibular canines had accessory canals. Conclusion. The root canal anatomy of permanent maxillary and mandibular canines varied widely in an Indian population.

  13. The effects of tumor location on diagnostic criteria for canine malignant peripheral nerve sheath tumors (MPNSTs) and the markers for distinction between canine MPNSTs and canine perivascular wall tumors. (United States)

    Suzuki, S; Uchida, K; Nakayama, H


    Canine malignant peripheral nerve sheath tumors (MPNSTs) occur not only in the peripheral nervous system (PNS) but also in soft tissue and various organs (non-PNS). The most important diagnostic criterion is proof of peripheral nerve sheath origin. This is difficult in non-PNS MPNSTs, and its differential diagnosis is challenging. Canine perivascular wall tumors (PWTs) also commonly arise in soft tissue. Their histopathological features are quite similar to those of canine MPNSTs, making their differential diagnosis challenging. To elucidate whether the morphological features are applicable to diagnose non-PNS MPNSTs and to demonstrate useful markers for distinction between canine MPNSTs and PWTs, the authors examined 30 canine MPNSTs and 31 PWTs immunohistochemically for S100, nestin, NGFR, Olig2, claudin-1, CD57, PRX, α-SMA, desmin, and calponin. Among canine MPNSTs, the PNS tumors displayed significantly higher S100 and Olig2 expression than the non-PNS tumors. The expression levels of the other markers did not differ significantly, suggesting that the same morphological diagnostic criteria are applicable regardless of their location. The PWT cells displayed significantly weaker immunoreactivity than MPNSTs to markers used except α-SMA and desmin. Cluster analysis sorted most canine MPNSTs and PWTs into 2 distinctly different clusters, whereas 3 MPNSTs and 6 PWTs were assigned to the opposing cluster. These 3 MPNSTs were negative for almost all markers, while these 6 PWTs were positive for only neuronal markers. In particular, NGFR and Olig2 were almost negative in the rest of PWT cases. These findings suggest that NGFR and Olig2 are useful to distinguish these 2 tumors.

  14. Glycolysis-related gene induction and ATP reduction during fractionated irradiation. Markers for radiation responsiveness of human tumor xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Goetze, K.; Meyer, S.S.; Mueller-Klieser, W. [University Medical Center Mainz Univ. (Germany). Inst. of Physiology and Pathophysiology; Yaromina, A. [Technical Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Zips, D. [University Hospital Tuebingen (Germany). Dept. of Radiation Oncology; Baumann, M. [Technical Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; University Hospital Dresden Technical Univ. Dresden (Germany). Dept. of Radiation Oncology


    Background and purpose: Lactate was previously shown to be a prognostic but not a predictive pre-therapeutic marker for radiation response of tumor xenografts. We hypothesize that metabolic changes during fractionated irradiation may restrict the predictiveness of lactate regarding tumor radiosensitivity. Materials and methods: Tumor xenografts were generated in nude mice by implanting 4 head and neck squamous cell carcinoma lines with different sensitivities to fractionated irradiation. Tumors were irradiated with up to 15 fractions of 2 Gy over a period of 3 weeks, and ATP and lactate levels were measured in vital tumor areas with induced metabolic bioluminescence imaging. Corresponding changes in mRNA expression of glycolysis-related genes were determined by quantitative RT-PCR. Results: Lactate content decreased significantly in 3 out of 4 cell lines in the course of irradiation showing no correlation with cell line-specific radiosensitivity. Radiation-induced changes in ATP levels and glycolysis-related mRNA expression, however, only occurred in radiosensitive or intermediately radioresistant xenografts, whereas these parameters remained unchanged in radioresistant tumors. Conclusion: Sensitivity-related differences in the transcriptional response of tumors to radiotherapy may be exploited in the clinic for better individualization of tumor treatment. (orig.)

  15. The Growth of SGC-7901 Tumor Xenografts Was Suppressed by Chinese Bayberry Anthocyanin Extract through Upregulating KLF6 Gene Expression (United States)

    Wang, Yue; Zhang, Xia-nan; Xie, Wen-hua; Zheng, Yi-xiong; Cao, Jin-ping; Cao, Pei-rang; Chen, Qing-jun; Li, Xian; Sun, Chong-de


    To investigate the antitumor effect of anthocyanins extracted from Chinese bayberry fruit (Myrica rubra Sieb. et Zucc.), a nude mouse tumor xenograft model was established. Treatments with C3G (cyanidin-3-glucoside, an anthocyanin) significantly suppressed the growth of SGC-7901 tumor xenografts in a dose-dependent manner. Immunohistochemical staining showed a significant increase in p21 expression, indicating that the cell cycle of tumor xenografts was inhibited. qPCR screening showed that C3G treatment up-regulated the expression of the KLF6 gene, which is an important tumor suppressor gene inactivated in many human cancers. Western blot showed that C3G treatments markedly increased KLF6 and p21 protein levels, inhibited CDK4 and Cyclin D1 expression, but did not notably change the expression of p53. These results indicated that KLF6 up-regulates p21 in a p53-independent manner and significantly reduces tumor proliferation. This study provides important information for the possible mechanism of C3G-induced antitumor activity against gastric adenocarcinoma in vivo. PMID:27690088

  16. The Growth of SGC-7901 Tumor Xenografts Was Suppressed by Chinese Bayberry Anthocyanin Extract through Upregulating KLF6 Gene Expression

    Directory of Open Access Journals (Sweden)

    Yue Wang


    Full Text Available To investigate the antitumor effect of anthocyanins extracted from Chinese bayberry fruit (Myrica rubra Sieb. et Zucc., a nude mouse tumor xenograft model was established. Treatments with C3G (cyanidin-3-glucoside, an anthocyanin significantly suppressed the growth of SGC-7901 tumor xenografts in a dose-dependent manner. Immunohistochemical staining showed a significant increase in p21 expression, indicating that the cell cycle of tumor xenografts was inhibited. qPCR screening showed that C3G treatment up-regulated the expression of the KLF6 gene, which is an important tumor suppressor gene inactivated in many human cancers. Western blot showed that C3G treatments markedly increased KLF6 and p21 protein levels, inhibited CDK4 and Cyclin D1 expression, but did not notably change the expression of p53. These results indicated that KLF6 up-regulates p21 in a p53-independent manner and significantly reduces tumor proliferation. This study provides important information for the possible mechanism of C3G-induced antitumor activity against gastric adenocarcinoma in vivo.

  17. An orthotopic xenograft model of intraneural NF1 MPNST suggests a potential association between steroid hormones and tumor cell proliferation. (United States)

    Perrin, George Q; Li, Hua; Fishbein, Lauren; Thomson, Susanne A; Hwang, Min S; Scarborough, Mark T; Yachnis, Anthony T; Wallace, Margaret R; Mareci, Thomas H; Muir, David


    Malignant peripheral nerve sheath tumors (MPNST) are the most aggressive cancers associated with neurofibromatosis type 1 (NF1). Here we report a practical and reproducible model of intraneural NF1 MPNST, by orthotopic xenograft of an immortal human NF1 tumor-derived Schwann cell line into the sciatic nerves of female scid mice. Intraneural injection of the cell line sNF96.2 consistently produced MPNST-like tumors that were highly cellular and showed extensive intraneural growth. These xenografts had a high proliferative index, were angiogenic, had significant mast cell infiltration and rapidly dominated the host nerve. The histopathology of engrafted intraneural tumors was consistent with that of human NF1 MPNST. Xenograft tumors were readily examined by magnetic resonance imaging, which also was used to assess tumor vascularity. In addition, the intraneural proliferation of sNF96.2 cell tumors was decreased in ovariectomized mice, while replacement of estrogen or progesterone restored tumor cell proliferation. This suggests a potential role for steroid hormones in supporting tumor cell growth of this MPNST cell line in vivo. The controlled orthotopic implantation of sNF96.2 cells provides for the precise initiation of intraneural MPNST-like tumors in a model system suitable for therapeutic interventions, including inhibitors of angiogenesis and further study of steroid hormone effects on tumor cell growth.

  18. Antitumor efficacy of lidamycin against human multiple myeloma RPMI 8226 cells and the xenograft in nonobese diabetic/severe combined immunodeficiency mice

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    Yongzhan Zhen


    Conclusions: LDM is highly effective against the growth of MM xenograft in NOD/SCID mice. The potent apoptosis.inducing effect of LDM may be mediated through caspase. and mitochondria.dependent pathway.

  19. Effect of tin etiopurpurin and light on the canine prostate (United States)

    Selman, Steven H.; Keck, Rick W.; Doiron, Daniel R.


    A series of experiments was undertaken to determine the effects of the combination of light and the tissue photosensitizer, tin etiopurpurin, on the canine prostate. Mongrel dogs were injected intravenously with 1.0 mg/kg of photosensitizer twenty-four hours prior to light delivery. Laser light, 660 nm, was administered either transurethrally or interstitially and tissue effects were assessed by histopathologic examination. Both techniques of light delivery resulted in hemorrhagic necrosis of the surrounding tissue. Photodynamic therapy may offer a novel approach to the treatment of both benign and malignant diseases of the prostate.

  20. A serological and bacteriological survey of canine brucellosis in Mexico. (United States)

    Flores-Castro, R; Segura, R


    Using agglutination procedures, 203 human and 500 dog sera collected in Mexico City were tested for canine brucellosis. Blood samples from the 500 dogs also were cultured for Brucella canis (B. canis). Positive agglutination titers (1:100 or greater) were found in 27 (13.3%) of the human and 140 (28.0%) of the dog sera tested. B. canis was isolated from the blood of eight dogs. The disease was experimentally produced in susceptible dogs by inoculation with one of the isolated strains.

  1. Nuclear morphometry in canine acanthomatous ameloblastomas and squamous cell carcinomas

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    M Martano


    Full Text Available The aim of this study was to evaluate whether morphometrical analysis can be of diagnostic value for canine acanthomatous ameloblastoma. We calculated, by means of an automated image analyser, some morphometric nuclear parameters, in particular: mean nuclear area (MNA, mean nuclear perimeter (MNP, maximum and minimum diameters (MDx and MDm coefficient of variation of the nuclear area (NACV, largest to smallest dimension ratio (LS ratio, and form factor (FF, in 8 canine acanthomatous ameloblastomas, and we compared these morphometric data to those of 13 squamous cell carcinomas of canine gingiva. The results indicated a progressive increase of the MNA, NACV, MNP and MDm proceeding from acanthomatous ameloblastomas (MNA: 42.11±8.74; NACV: 28,36±7,23; MNP: 24.18± 2.68; MDm: 5.69±0.49 to squamous cell carcinomas (MNA:49,69±9,10; NACV: 30,89±7,75; MNP: 25.63±2.54; MDm: 6.64±0.73. On the contrary, the LS ratio and the FF resulted greater in acanthomatous ameloblastomas (LS ratio: 1,63±0,12; FF: 1,13±0,002 than in SCCs (LS ratio: 1,40±0,12; FF:0.91±0.38. Moreover, the MNA, MNP,MDx and MDm resulted similar (MNA: p=0.89; MNP: p=0,65; MDm: p=0,16; MDx: p=0,13 in a subset of four acanthomatous ameloblastomas with cellular atypia (MNA:49,01±6,88; MNP: 26,28±1,99; MDm: 6.08±0.41; MDx: 10.18±0.88 and in squamous cell carcinomas (MNA:49.69±9,10; MNP: 25.63±2.54; MDm: 6.64±0.73; MDx: 9.26±1.05. While the NACV values resulted higher in typical acanthomatous ameloblastoma (29,99±6,06 than in atypical acanthomatous ameloblastoma (26,74±8,84 and similar to those of the SCCs (30,89±7,75. These results seem to confirm that acanthomatous ameloblastoma is a malignant or potentially malignant lesion and emphasizes that nuclear morphometry analysis can be an useful diagnostic and prognostic method in canine oral pathology.

  2. Occurrence of different Canine distemper virus lineages in Italian dogs. (United States)

    Balboni, Andrea; De Lorenzo Dandola, Giorgia; Scagliarini, Alessandra; Prosperi, Santino; Battilani, Mara


    This study describes the sequence analysis of the H gene of 7 Canine distemper virus (CDV) strains identified in dogs in Italy between years 2002-2012. The phylogenetic analysis showed that the CDV strains belonged to 2 clusters: 6 viruses were identified as Arctic-like lineage and 1 as Europe 1 lineage. These data show a considerable prevalence of Arctic-like-CDVs in the analysed dogs. The dogs and the 3 viruses more recently identified showed 4 distinctive amino acid mutations compared to all other Arctic CDVs.

  3. 125I seed irradiation induces up-regulation of the genes associated with apoptosis and cell cycle arrest and inhibits growth of gastric cancer xenografts



    Abstract Background Iodine 125 (125I) seed irradiation can be used as an important supplementary treatment for unresectable advanced gastric cancer. Here, we aim to comprehensively elucidate the biological effects induced by 125I seed irradiation in human gastric cancer xenograft model by using global expression and DNA methylation analyses. Methods The 48 mice bearing NCI-N87 gastric cancer xenografts were randomly separated into 2 groups: sham seeds (O mCi) were implanted into the control g...

  4. Appropriateness of using patient-derived xenograft models for pharmacologic evaluation of novel therapies for esophageal/gastro-esophageal junction cancers.

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    Lorin Dodbiba

    Full Text Available The high morbidity and mortality of patients with esophageal (E and gastro-esophageal junction (GEJ cancers, warrants new pre-clinical models for drug testing. The utility of primary tumor xenografts (PTXGs as pre-clinical models was assessed. Clinicopathological, immunohistochemical markers (p53, p16, Ki-67, Her-2/neu and EGFR, and global mRNA abundance profiles were evaluated to determine selection biases of samples implanted or engrafted, compared with the underlying population. Nine primary E/GEJ adenocarcinoma xenograft lines were further characterized for the spectrum and stability of gene/protein expression over passages. Seven primary esophageal adenocarcinoma xenograft lines were treated with individual or combination chemotherapy. Tumors that were implanted (n=55 in NOD/SCID mice had features suggestive of more aggressive biology than tumors that were never implanted (n=32. Of those implanted, 21/55 engrafted; engraftment was associated with poorly differentiated tumors (p=0.04 and older patients (p=0.01. Expression of immunohistochemical markers were similar between patient sample and corresponding xenograft. mRNA differences observed between patient tumors and first passage xenografts were largely due to loss of human stroma in xenografts. mRNA patterns of early vs late passage xenografts and of small vs large tumors of the same passage were similar. Complete resistance was present in 2/7 xenografts while the remaining tumors showed varying degrees of sensitivity, that remained constant across passages. Because of their ability to recapitulate primary tumor characteristics during engraftment and across serial passaging, PTXGs can be useful clinical systems for assessment of drug sensitivity of human E/GEJ cancers.

  5. Generation of Pediatric Leukemia Xenograft Models in NSG-B2m Mice: Comparison with NOD/SCID Mice. (United States)

    Gopalakrishnapillai, Anilkumar; Kolb, E Anders; Dhanan, Priyanka; Bojja, Aruna Sri; Mason, Robert W; Corao, Diana; Barwe, Sonali P


    Generation of orthotopic xenograft mouse models of leukemia is important to understand the mechanisms of leukemogenesis, cancer progression, its cross talk with the bone marrow microenvironment, and for preclinical evaluation of drugs. In these models, following intravenous injection, leukemic cells home to the bone marrow and proliferate there before infiltrating other organs, such as spleen, liver, and the central nervous system. Moreover, such models have been shown to accurately recapitulate the human disease and correlate with patient response to therapy and prognosis. Thus, various immune-deficient mice strains have been used with or without recipient preconditioning to increase engraftment efficiency. Mice homozygous for the severe combined immune deficiency (SCID) mutation and with non-obese diabetic background (NOD/SCID) have been used in the majority of leukemia xenograft studies. Later, NOD/SCID mice deficient for interleukin 2 receptor gamma chain (IL2Rγ) gene called NSG mice became the model of choice for leukemia xenografts. However, engraftment of leukemia cells without irradiation preconditioning still remained a challenge. In this study, we used NSG mice with null alleles for major histocompatibility complex class I beta2-microglobulin (β2m) called NSG-B2m. This is a first report describing the 100% engraftment efficiency of pediatric leukemia cell lines and primary samples in NSG-B2m mice in the absence of host preconditioning by sublethal irradiation. We also show direct comparison of the engraftment efficiency and growth rate of pediatric acute leukemia cells in NSG-B2m and NOD/SCID mice, which showed 80-90% engraftment efficiency. Secondary and tertiary xenografts in NSG-B2m mice generated by injection of cells isolated from the spleens of leukemia-bearing mice also behaved similar to the primary patient sample. We have successfully engrafted 25 acute lymphoblastic leukemia (ALL) and 5 acute myeloid leukemia (AML) patient samples with

  6. Photodynamic therapy with the phthalocyanine photosensitizer Pc 4 of SW480 human colon cancer xenografts in athymic mice. (United States)

    Whitacre, C M; Feyes, D K; Satoh, T; Grossmann, J; Mulvihill, J W; Mukhtar, H; Oleinick, N L


    Photodynamic therapy (PDT) using the silicon phthalocyanine photosensitizer Pc 4 [HOSiPcOSi(CH3)2(CH2)3N-(CH3)2] is an oxidative stress associated with induction of apoptosis in various cell types. We assessed the effectiveness of Pc 4-PDT on SW480 colon cancer xenografts grown in athymic nude mice. Animals bearing xenografts were treated with 1 mg/kg body weight Pc 4 and 48 h later were irradiated with 150 J/cm2 672-nm light from a diode laser delivered at 150 mW/cm2. Biochemical studies were performed in xenografts resected at various time points up to 26 h after Pc 4-PDT treatment, whereas tumor size was evaluated over a 4-week period in parallel experiments. In the tumors resected for biochemical studies, apoptosis was visualized by activation of caspase-9 and caspase-3 and a gradual increase in the cleavage of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) to a maximum of approximately 60% of the total PARP present at approximately 26 h. At that time all Pc 4-PDT-treated tumors had regressed significantly. Two signaling responses that have previously been shown to be associated with Pc 4-PDT-induced apoptosis in cultured cells, p38 mitogen-activated protein kinase and p21/WAF1/Cip1, were examined. A marked increase in phosphorylation of p38 was observed within 1 h after Pc 4-PDT without changes in levels of the p38 protein. Levels of p21 were not altered in the xenografts in correspondence with the presence of mutant p53 in SW480 cells. Evaluation of tumor size showed that tumor growth resumed after a delay of 9-15 days. Our results suggest that: (a) Pc 4-PDT is effective in the treatment of SW480 human colon cancer xenografts independent of p53 status; (b) PARP cleavage may be mediated by caspase-9 and caspase-3 activation in the Pc 4-PDT-treated tumors; and (c) p38 phosphorylation may be a trigger of apoptosis in response to PDT in vivo in this tumor model.

  7. Impacted maxillary canine on the position of the central incisor: surgical-orthodontic repositioning. (United States)

    Farronato, G; Giannini, L; Folegatti, C; Brotto, E; Galbiati, G; Maspero, C


    The aim of this article is to describe a case of a young orthodontic patient in which an impacted maxillary canine was repositioned in the central incisor position. A severe resorption of the root of the central right maxillary incisor by ectopic eruption of the impacted right maxillary canine is described. The canine was repositioned in the incisor's position to avoid resorption of the roots of the adjacent teeth during the disinclusion. The central incisor was extracted and the canine was extruded by a closed eruption technique. When the canine eruption was complete, the tip, the torque and the morphology of the canine were modified in order to make it look like an incisor. Nowadays the therapy with dental implants is the best choice, if the position of impacted teeth is difficult to reach. This case report describes a successful management of an impacted upper right canine aligned in the upper right central incisor position. Accurate diagnosis, conservative management of the soft tissues, anchorage unit and the direction of the orthodontic traction are important factors for the success treatment.

  8. Novel canine bocavirus strain associated with severe enteritis in a dog litter. (United States)

    Bodewes, Rogier; Lapp, Stefanie; Hahn, Kerstin; Habierski, André; Förster, Christine; König, Matthias; Wohlsein, Peter; Osterhaus, Albert D M E; Baumgärtner, Wolfgang


    Bocaviruses are small non-enveloped viruses with a linear ssDNA genome, that belong to the genus Bocaparvovirus of the subfamiliy Parvovirinae. Bocavirus infections are associated with a wide spectrum of disease in humans and various mammalian species. Here we describe a fatal enteritis associated with infection with a novel strain of canine bocavirus 2 (CaBoV-2), that occurred in a litter of German wirehaired pointers. Necropsy performed on three puppies revealed an enteritis reminiscent of canine parvovirus associated enteritis, accompanied with signs of lymphocytolytic disease in bone marrow, spleen, lymph nodes and thymus. While other major causes of enteritis of young dogs, including canine parvovirus, were excluded, by random PCR in combination with next-generation sequencing, a novel CaBoV-2 strain was detected. Phylogenetic analysis of the genome of this novel canine bocavirus strain indicated that this virus was indeed most closely related to group 2 canine bocaviruses. Infection with canine bocavirus was confirmed by in situ hybridization, which revealed the presence of CaBoV-2 nucleic acid in the intestinal tract and lymphoid tissues of the dogs. In a small-scale retrospective analysis concerning the role of CaBoV-2 no additional cases were identified. The findings of this study provide novel insights into the pathogenicity of canine bocaviruses.

  9. Detection of novel papillomaviruses in canine mucosal, cutaneous and in situ squamous cell carcinomas. (United States)

    Zaugg, N; Nespeca, G; Hauser, B; Ackermann, M; Favrot, C


    Papillomavirus (PV) DNA is frequently uncovered in samples of human skin squamous cell carcinomas (SCC). However, the role of these viruses in the development of such cancers in canine species remains controversial. While approximately 100 human PVs are known, only one single canine oral PV (COPV) has been identified and studied extensively. Therefore, we applied a narrow-range polymerase chain reaction (PCR) suitable for the detection of classical canine and feline PVs, as well as a broad-range PCR, which has been used for the detection of various novel PVs in humans, in order to analyse 42 paraffin-embedded samples, representing three different forms of canine SCCs. Ten samples of skin tissues with various non-neoplastic conditions served as controls. While none of the negative controls reacted positively, PV DNA was discovered in 21% of the tested SCC samples. Interestingly, the classical COPV was amplified from only one sample, while the other positive cases were associated with a variety of thus far unknown PVs. This study suggests that a fraction of canine SCC is infected with PVs and that a genetic variety of canine PVs exists. Therefore, these results will facilitate the future study of the role of PVs in the development of canine skin cancers.

  10. Biocompatibility and osteoconductivity of injectable bone xenograft, hydroxyapatite and hydroxyapatite-chitosan on osteoblast culture

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    Bachtiar EW


    Full Text Available Background: Bone graft in the form of injectable paste gives several advantages over the powder form as it could be placed in the defect area that has limited accessibility. Purpose: The purpose of this study was to assess biocompatibility and osteoconductivity of an injectable bone xenograft (IBX, injectable hydroxyapatite (IHA and injectable hydroxyapatite-chitosan (IHA-C on osteoblastic cell line (MG-63. Methods: Three concentrations (0.25%, 0.5% and 1.0% of IBX, IHA and IHA-C were supplemented with DMEM culture medium. The viability cells were measured by MTT assay 4 hour after incubation. ALP activity was measured at day 1, 3, 5 and 7. Calcium deposition was tested at day 3 and day 7 by means of Von Kossa staining. Results: MTT assay showed that the viability cells of all the test groups were above 100% compared to the control group. The cell viability of the 0.25% IHA paste was significantly higher (115.02% ± 4.37%, p < 0.05 compared with IBX paste and IHA-C in all concentrations tested. The highest level of ALP secretion of all test groups was found on the fifth day of exposure. The highest level of ALP in the IBX paste group was 0.25% concentration while the highest level of ALP in the IHA-C and IHA paste group was 1% and 0.25%, respectively. In addition, the highest calcium deposition was shown on IHA 1% at day 7 (p > 0.05. Conclusion: It was suggested that adequate biocompatibility and osteoconductivity was evident for all injectable pastes tested.Latar belakang: Bahan tandur tulang dalam bentuk pasta injeksi memiliki kelebihan dibandingkan bila bahan tersebut berupa bubuk, karena lebih mudah diaplikasikan pada daerah yang sulit dijangkau. Tujuan: Penelitian ini bertujuan untuk mengamati sifat biokompatibilitas dan osteokonduktifitas biomaterial tandur tulang dalam bentuk injectable bone xenograft (IBX, injectable hydroxyapatite (IHA dan injectable hydroxyapatite-chitosan (IHA-C pada galur sel osteoblas (MG-63. Metode: Bahan tandur

  11. Antitumor activity of celastrol nanoparticles in a xenograft retinoblastoma tumor model

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    Li ZR


    Full Text Available Zhanrong Li,1,* Xianghua Wu,1,* Jingguo Li,2 Lin Yao,1 Limei Sun,1 Yingying Shi,1 Wenxin Zhang,1 Jianxian Lin,1 Dan Liang,1 Yongping Li1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, 2School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of China*These authors contributed equally to this workBackground: Celastrol, a Chinese herbal medicine, has shown antitumor activity against various tumor cell lines. However, the effect of celastrol on retinoblastoma has not yet been analyzed. Additionally, the poor water solubility of celastrol restricts further therapeutic applications. The goal of this study was to evaluate the effect of celastrol nanoparticles (CNPs on retinoblastoma and to investigate the potential mechanisms involved.Methods: Celastrol-loaded poly(ethylene glycol-block-poly(ε-caprolactone nanopolymeric micelles were developed to improve the hydrophilicity of celastrol. The 2-(2-methoxy-4-nitrophenyl-3-(4-nitrophenyl-5-(2,4-disulf-ophenyl-2H tetrazolium monosodium salt (WST-8 assay was used to determine the inhibitory effect of CNPs on SO-Rb 50 cell proliferation in vitro. Immunofluorescence was used to evaluate the apoptotic effect of CNPs on nuclear morphology, and flow cytometry was used to quantify cellular apoptosis. The expression of Bcl-2, Bax, NF-κB p65, and phospo-NF-κB p65 proteins was assessed by Western blotting. A human retinoblastoma xenograft model was used to evaluate the inhibitory effects of CNPs on retinoblastoma in NOD-SCID mice. Hematoxylin and eosin staining was used to assess the apoptotic effects of CNPs on retinoblastoma.Results: CNPs inhibit the proliferation of SO-Rb 50 cells in a dose- and time-dependent manner with an IC50 of 17.733 µg/mL (celastrol-loading content: 7.36% after exposure to CNPs for 48 hours. CNPs induce apoptosis in SO-Rb 50 cells in a dose-dependent manner. The expression of Bcl-2, NF-κB p65, and phospo-NF-κB p65

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

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    Kiupel Matti


    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.

  13. New hominin fossils from Kanapoi, Kenya, and the mosaic evolution of canine teeth in early hominins

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    J. Michael Plavcan


    Full Text Available Whilst reduced size, altered shape and diminished sexual dimorphism of the canine–premolar complex are diagnostic features of the hominin clade, little is known about the rate and timing of changes in canine size and shape in early hominins. The earliest Australopithecus, Australopithecus anamensis, had canine crowns similar in size to those of its descendant Australopithecus afarensis, but a single large root alveolus has suggested that this species may have had larger and more dimorphic canines than previously recognised. Here we present three new associated dentitions attributed to A. anamensis, recently recovered from the type site of Kanapoi, Kenya, that provide evidence of canine evolution in early Australopithecus. These fossils include the largest mandibular canine root in the hominin fossil record. We demonstrate that, although canine crown height did not differ between these species, A. anamensis had larger and more dimorphic roots, more like those of extant great apes and Ardipithecus ramidus, than those of A. afarensis. The canine and premolar occlusal shapes of A. anamensis also resemble those of Ar. ramidus, and are intermediary between extant great apes and A. afarensis. A. afarensis achieved Homo-like maxillary crown basal proportions without a reduction in crown height. Thus, canine crown size and dimorphism remained stable during the early evolution of Australopithecus, but mandibular root dimensions changed only later within the A. anamensis–afarensis lineage, coincident with morphological changes in the canine–premolar complex. These observations suggest that selection on canine tooth crown height, shape and root dimensions was not coupled in early hominin evolution, and was not part of an integrated adaptive package.

  14. Canine reduction in the miocene hominoid Oreopithecus bambolii: behavioural and evolutionary implications. (United States)

    Alba, D M; Moyà-Solà, S; Köhler, M


    The degree of canine size sexual dimorphism and relative canine size, which have been related to levels of agonistic behaviour amongst living anthropoid primates, together with relative molar size, are evaluated in the fossil hominoid Oreopithecus bambolii from the Late Miocene of Italy. Although Oreopithecus displays a significant degree of canine height sexual dimorphism, using allometric techniques and body mass estimates for fossil species, it is shown that Oreopithecus males are microdont (smaller postcanine as well as canine teeth than expected) when compared to most living hominoids and its putative ancestor Dryopithecus. Canine reduction in Oreopithecus includes both crown height and, especially, basal area, and most closely resembles the condition found in the pygmy chimpanzee Pan paniscus. Interestingly, it had been previously proposed that Oreopithecus displays, like pygmy chimpanzees, a paedomorphic cranial morphology resulting in a reduction of facial prognathism, which could be related to microdontia in both taxa. Independent canine reduction in several anthropoid lineages (including hominids and P. paniscus) has been related to a relaxation of the selection pressure favouring canine use as a weapon. Although changes in socio-sexual behaviour, as documented in P. paniscus, cannot be currently discarded in Oreopithecus, canine reduction could be also alternatively (although not exclusively) interpreted as an aspect of generalized microdontia. The latter is best considered an adaptive readjustment required by the paedomorphic reduction of prognathism and the resulting lack of space to accommodate the adult dentition. This mechanism of canine reduction highlights the significance of developmental constraints in evolution and had not been previously suggested for any anthropoid primate.

  15. Comprehensive analysis of leukocytes, vascularization and matrix metalloproteinases in human menstrual xenograft model. (United States)

    Guo, Yong; He, Bin; Xu, Xiangbo; Wang, Jiedong


    In our previous study, menstrual-like changes in mouse were provoked through the pharmacologic withdrawal of progesterone with mifepristone following induction of decidualization. However, mouse is not a natural menstruation animal, and the menstruation model using external stimuli may not truly reflect the occurrence and development of the human menstrual process. Therefore, we established a model of menstruation based on human endometrial xenotransplantation. In this model, human endometrial tissues were transplanted subcutaneously into SCID mice that were ovarectomized and supplemented with estrogen and progestogen by silastic implants with a scheme imitating the endocrinological milieu of human menstrual cycle. Morphology, hormone levels, and expression of vimentin and cytokeratin markers were evaluated to confirm the menstrual-like changes in this model. With 28 days of hormone treatment, transplanted human endometrium survived and underwent proliferation, differentiation and disintegration, similar to human endometrium in vivo. Human CD45+ cells showed a peak of increase 28 days post-transplantation. Three days after progesterone withdrawal, mouse CD45+ cells increased rapidly in number and were significantly greater than human CD45+ cell counts. Mouse CD31+ blood vascular-like structures were detected in both transplanted and host tissues. After progesterone withdrawal, the expression levels of matrix metalloproteinases (MMP) 1, 2, and 9 were increased. In summary, we successfully established a human endometrial xenotransplantation model in SCID mice, based on the results of menstrual-like changes in which MMP-1, 2 and 9 are involved. We showed that leukocytes are originated from in situ proliferation in human xenografts and involved in the occurrence of menstruation. This model will help to further understand the occurrence, growth, and differentiation of the endometrium and the underlying mechanisms of menstruation.

  16. Monitoring PAI-1 and VEGF Levels in 6 Human Squamous Cell Carcinoma Xenografts During Fractionated Irradiation

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    Bayer, Christine, E-mail: [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Kielow, Achim [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Schilling, Daniela [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden (Germany); Maftei, Constantin-Alin [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Zips, Daniel; Yaromina, Ala; Baumann, Michael [OncoRay Center for Radiation Research, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden (Germany); Molls, Michael [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Multhoff, Gabriele [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden (Germany)


    Purpose: Previous studies have shown that the plasminogen activator inhibitor type-1 (PAI-1) and vascular endothelial growth factor (VEGF) are regulated by hypoxia and irradiation and are involved in neoangiogenesis. The aim of this study was to determine in vivo whether changes in PAI-1 and VEGF during fractionated irradiation could predict for radiation resistance. Methods and Materials: Six xenografted tumor lines from human squamous cell carcinomas (HSCC) of the head and neck were irradiated with 0, 3, 5, 10, and 15 daily fractions of 2 Gy. The PAI-1 and VEGF antigen levels in tumor lysates were determined by enzyme-linked immunosorbent assay kits. The amounts of PAI-1 and VEGF were compared with the dose to cure 50% of tumors (TCD{sub 50}). Colocalization of PAI-1, pimonidazole (hypoxia), CD31 (endothelium), and Hoechst 33342 (perfusion) was examined by immunofluorescence. Results: Human PAI-1 and VEGF (hVEGF) expression levels were induced by fractionated irradiation in UT-SCC-15, UT-SCC-14, and UT-SCC-5 tumors, and mouse VEGF (msVEGF) was induced only in UT-SCC-5 tumors. High hVEGF levels were significantly associated with radiation sensitivity after 5 fractions (P=.021), and high msVEGF levels were significantly associated with radiation resistance after 10 fractions (P=.007). PAI-1 staining was observed in the extracellular matrix, the cytoplasm of fibroblast-like stroma cells, and individual tumor cells at all doses of irradiation. Colocalization studies showed PAI-1 staining close to microvessels. Conclusions: These results indicate that the concentration of tumor-specific and host-specific VEGF during fractionated irradiation could provide considerably divergent information for the outcome of radiation therapy.

  17. Chick embryo xenograft model reveals a novel perineural niche for human adipose-derived stromal cells

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    Ingrid R. Cordeiro


    Full Text Available Human adipose-derived stromal cells (hADSC are a heterogeneous cell population that contains adult multipotent stem cells. Although it is well established that hADSC have skeletal potential in vivo in adult organisms, in vitro assays suggest further differentiation capacity, such as into glia. Thus, we propose that grafting hADSC into the embryo can provide them with a much more instructive microenvironment, allowing the human cells to adopt diverse fates or niches. Here, hADSC spheroids were grafted into either the presumptive presomitic mesoderm or the first branchial arch (BA1 regions of chick embryos. Cells were identified without previous manipulations via human-specific Alu probes, which allows efficient long-term tracing of heterogeneous primary cultures. When grafted into the trunk, in contrast to previous studies, hADSC were not found in chondrogenic or osteogenic territories up to E8. Surprisingly, 82.5% of the hADSC were associated with HNK1+ tissues, such as peripheral nerves. Human skin fibroblasts showed a smaller tropism for nerves. In line with other studies, hADSC also adopted perivascular locations. When grafted into the presumptive BA1, 74.6% of the cells were in the outflow tract, the final goal of cardiac neural crest cells, and were also associated with peripheral nerves. This is the first study showing that hADSC could adopt a perineural niche in vivo and were able to recognize cues for neural crest cell migration of the host. Therefore, we propose that xenografts of human cells into chick embryos can reveal novel behaviors of heterogeneous cell populations, such as response to migration cues.

  18. Obesity does not promote tumorigenesis of localized patient-derived prostate cancer xenografts (United States)

    Ascui, Natasha; Frydenberg, Mark; Risbridger, Gail P.; Taylor, Renea A.; Watt, Matthew J.


    There are established epidemiological links between obesity and the severity of prostate cancer. We directly tested this relationship by assessing tumorigenicity of patient-derived xenografts (PDXs) of moderate-grade localized prostate cancer in lean and obese severe combined immunodeficiency (SCID) mice. Mice were rendered obese and insulin resistant by high-fat feeding for 6 weeks prior to transplantation, and PDXs were assessed 10 weeks thereafter. Histological analysis of PDX grafts showed no differences in tumor pathology, prostate-specific antigen, androgen receptor and homeobox protein Nkx-3.1 expression, or proliferation index in lean versus obese mice. Whilst systemic obesity per se did not promote prostate tumorigenicity, we next asked whether the peri-prostatic adipose tissue (PPAT), which covers the prostate anteriorly, plays a role in prostate tumorigenesis. In vitro studies in a cellularized co-culture model of stromal and epithelial cells demonstrated that factors secreted from human PPAT are pro-tumorigenic. Accordingly, we recapitulated the prostate-PPAT spatial relationship by co-grafting human PPAT with prostate cancer in PDX grafts. PDX tissues were harvested 10 weeks after grafting, and histological analysis revealed no evidence of enhanced tumorigenesis with PPAT compared to prostate cancer grafts alone. Altogether, these data demonstrate that prostate cancer tumorigenicity is not accelerated in the setting of diet-induced obesity or in the presence of human PPAT, prompting the need for further work to define the at-risk populations of obesity-driven tumorigenesis and the biological factors linking obesity, adipose tissue and prostate cancer pathogenesis. PMID:27351281

  19. Inhibition of leukemic cells by valproic acid, an HDAC inhibitor, in xenograft tumors

    Directory of Open Access Journals (Sweden)

    Zhang Z


    Full Text Available Zhihua Zhang,1 Changlai Hao,1 Lihong Wang,1 Peng Liu,2 Lei Zhao,1 Cuimin Zhu,1 Xia Tian31Hematology Department, Affiliated Hospital of Chengde Medical College, Chengde, Hebei Province, 2Department of Medical Oncology, Shijiazhuang Municipal No 1 Hospital, Hebei Province, 3Department of Medical Oncology, Rizhao Municipal People’s Hospital, Shandong Province, People's Republic of ChinaAbstract: The chimeric fusion protein, AML1-ETO, generated by translocation of t(8;21, abnormally recruits histone deacetylase (HDAC to the promoters of AML1 target genes, resulting in transcriptional repression of the target genes and development of t(8;21 acute myeloid leukemia. Abnormal expression of cyclin-dependent kinase inhibitors, especially p21, is considered a possible mechanism of the arrested maturation and differentiation seen in leukemia cells. A new generation of HDAC inhibitors is becoming an increasing focus of attention for their ability to induce differentiation and apoptosis in tumor cells and to block the cell cycle. Our previous research had demonstrated that valproic acid induces G0/G1 arrest of Kasumi-1 cells in t(8;21 acute myeloid leukemia. In this study, we further confirmed that valproic acid inhibits the growth of Kasumi-1 cells in a murine xenograft tumor model, and that this occurs via upregulation of histone acetylation in the p21 promoter region, enhancement of p21 expression, suppression of phosphorylation of retinoblastoma protein, blocking of transcription activated by E2F, and induction of G0/G1 arrest.Keywords: valproic acid, acute myeloid leukemia, AML1-ETO, p21, E2F

  20. Monitoring longitudinal changes in irradiated head and neck cancer xenografts using diffuse reflectance spectroscopy (United States)

    Vishwanath, Karthik; Jiang, Shudong; Gunn, Jason R.; Marra, Kayla; Andreozzi, Jacqueline M.; Pogue, Brian W.


    Radiation therapy is often used as the preferred clinical treatment for control of localized head and neck cancer. However, during the course of treatment (6-8 weeks), feedback about functional and/or physiological changes within impacted tissue are not obtained, given the onerous financial and/or logistical burdens of scheduling MRI, PET or CT scans. Diffuse optical sensing is well suited to address this problem since the instrumentation can be made low-cost and portable while still being able to non-invasively provide information about vascular oxygenation in vivo. Here we report results from studies that employed an optical fiber-based portable diffuse reflectance spectroscopy (DRS) system to longitudinally monitor changes in tumor vasculature within two head and neck cancer cell lines (SCC-15 and FaDu) xenografted in the flanks of nude mice, in two separate experiments. Once the tumor volumes were 100mm3, 67% of animals received localized (electron beam) radiation therapy in five fractions (8Gy/day, for 5 days) while 33% of the animals served as controls. DRS measurements were obtained from each animal on each day of treatment and then for two weeks post-treatment. Reflectance spectra were parametrized to extract total hemoglobin concentration and blood oxygen-saturation and the resulting time-trends of optical parameters appear to be dissimilar for the two cell-lines. These findings are also compared to previous animal experiments (using the FaDu line) that were irradiated using a photon beam radiotherapy protocol. These results and implications for the use of fiber-based DRS measurements made at local (irradiated) tumor site as a basis for identifying early radiotherapy-response are presented and discussed.

  1. Mitotane effects in a H295R xenograft model of adjuvant treatment of adrenocortical cancer. (United States)

    Lindhe, O; Skogseid, B


    Adrenocortical cancer is one of the most aggressive endocrine malignancies. Growth through the capsule or accidental release of cancer cells during surgery frequently results in metastatic disease. We investigated the antitumoral effect of 2 adrenocorticolytic compounds, O, P'-DDD and MeSO2-DDE, in the adrenocortical cell line H295R both in vitro and as a xenograft model in vivo. H295R cells were injected s. c. in nude mice. O, P'-DDD, MeSO2-DDE, or oil (control) was administered i. p., either simultaneously with cell injection at day 0 (mimicking adjuvant treatment), or at day 48 (established tumors). Accumulation of PET tracers [ (11)C]methionine (MET), [ (11)C] metomidate (MTO), 2-deoxy-2-[ (18)F]fluoro-d-glucose (FDG), and [ (18)F]-l-tyrosine (FLT) in the aggregates were assessed +/- drug treatment in vitro. Tumor growth was significantly inhibited when O, P'-DDD was given at the same time as injection of tumor cells. No significant growth inhibition was observed after treatment with O, P'-DDD at day 48. A significant reduction in FLT uptake and an increased FDG uptake, compared to control, were observed following treatment with 15 microM O, P'-DDD (p<0.01) in vitro. MeSO2-DDE (15 microM) treatment gave rise to a reduced MET and an increased FLT uptake (p<0.01). Both compounds reduced the uptake of MTO compared to control (p<0.01). Treatment with O, P'-DDD simultaneously to inoculation of H295R cells in mice, imitating release of cells during surgery, gave a markedly better effect than treatment of established H295R tumors. We suggest that FLT may be a potential PET biomarker when assessing adrenocortical cancer treatment with O,P'-DDD. Further studies in humans are needed to investigate this.

  2. Dynamics of genomic clones in breast cancer patient xenografts at single cell resolution (United States)

    Eirew, Peter; Steif, Adi; Khattra, Jaswinder; Ha, Gavin; Yap, Damian; Farahani, Hossein; Gelmon, Karen; Chia, Stephen; Mar, Colin; Wan, Adrian; Laks, Emma; Biele, Justina; Shumansky, Karey; Rosner, Jamie; McPherson, Andrew; Nielsen, Cydney; Roth, Andrew J. L.; Lefebvre, Calvin; Bashashati, Ali; de Souza, Camila; Siu, Celia; Aniba, Radhouane; Brimhall, Jazmine; Oloumi, Arusha; Osako, Tomo; Bruna, Alejandra; Sandoval, Jose; Algara, Teresa; Greenwood, Wendy; Leung, Kaston; Cheng, Hongwei; Xue, Hui; Wang, Yuzhuo; Lin, Dong; Mungall, Andrew J.; Moore, Richard; Zhao, Yongjun; Lorette, Julie; Nguyen, Long; Huntsman, David; Eaves, Connie J.; Hansen, Carl; Marra, Marco A.; Caldas, Carlos; Shah, Sohrab P.; Aparicio, Samuel


    Human cancers, including breast cancers, are comprised of clones differing in mutation content. Clones evolve dynamically in space and time following principles of Darwinian evolution1,2, underpinning important emergent features such as drug resistance and metastasis3–7. Human breast cancer xenoengraftment is used as a means of capturing and studying tumour biology, and breast tumour xenografts are generally assumed to be reasonable models of the originating tumours8–10. However the consequences and reproducibility of engraftment and propagation on the genomic clonal architecture of tumours has not been systematically examined at single cell resolution. Here we show by both deep genome and single cell sequencing methods, the clonal dynamics of initial engraftment and subsequent serial propagation of primary and metastatic human breast cancers in immunodeficient mice. In all 15 cases examined, clonal selection on engraftment was observed in both primary and metastatic breast tumours, varying in degree from extreme selective engraftment of minor (<5% of starting population) clones to moderate, polyclonal engraftment. Furthermore, ongoing clonal dynamics during serial passaging is a feature of tumours experiencing modest initial selection. Through single cell sequencing, we show that major mutation clusters estimated from tumour population sequencing relate predictably to the most abundant clonal genotypes, even in clonally complex and rapidly evolving cases. Finally, we show that similar clonal expansion patterns can emerge in independent grafts of the same starting tumour population, indicating that genomic aberrations can be reproducible determinants of evolutionary trajectories. Our results show that measurement of genomically defined clonal population dynamics will be highly informative for functional studies utilizing patient-derived breast cancer xenoengraftment. PMID:25470049

  3. Tumour xenograft detection through quantitative analysis of the metabolic profile of urine in mice

    Energy Technology Data Exchange (ETDEWEB)

    Moroz, Jennifer [Department of Physics, University of Alberta, 11322-89 Avenue, Edmonton, Alberta T6G 2G7 (Canada); Turner, Joan [Department of Experimental Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Slupsky, Carolyn [Department of Nutrition, University of California, One Shields Avenue, Davis, CA 95616-8598 (United States); Fallone, Gino; Syme, Alasdair, E-mail: [Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada)


    The metabolic content of urine from NIH III nude mice (n = 22) was analysed before and after inoculation with human glioblastoma multiforme (GBM) cancer cells. An age- and gender-matched control population (n = 14) was also studied to identify non-tumour-related changes. Urine samples were collected daily for 6 weeks, beginning 1 week before cell injection. Metabolite concentrations were obtained via targeted profiling with Chenomx Suite 5.1, based on nuclear magnetic resonance (NMR) spectra acquired on an Oxford 800 MHz cold probe NMR spectrometer. The Wilcoxon rank sum test was used to evaluate the significance of the change in metabolite concentration between the two time points. Both the metabolite concentrations and the ratios of pairs of metabolites were studied. The complicated inter-relationships between metabolites were assessed through partial least-squares discriminant analysis (PLS-DA). Receiver operating characteristic (ROC) curves were generated for all variables and the area under the curve (AUC) calculated. The data indicate that the number of statistically significant changes in metabolite concentrations was more pronounced in the tumour-bearing population than in the control animals. This was also true of the ratios of pairs of metabolites. ROC analysis suggests that the ratios were better able to differentiate between the pre- and post-injection samples compared to the metabolite concentrations. PLS-DA models produced good separation between the populations and had the best AUC results (all models exceeded 0.937). These results demonstrate that metabolomics may be used as a screening tool for GBM cells grown in xenograft models in mice.

  4. Enhancement of monoclonal antibody uptake in human colon tumor xenografts following irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kalofonos, H.; Rowlinson, G.; Epenetos, A.A. (Royal Postgraduate Medical School, London (England))


    Indium-111-labeled AUA1 tumor-associated monoclonal antibody raised against an antigen of colon adenocarcinoma was used to evaluate the effect of ionizing radiation on antibody uptake by the LoVo adenocarcinoma cell line grown as a xenograft in nude mice. Tumors were exposed to single doses of external X-irradiation of between 400 and 1600 cGy followed, 24 h later, by administration of specific or nonspecific antibody. Animals were sacrificed 3 days after antibody administration. At doses higher than 400 cGy, tumor uptake with both specific and nonspecific antibody was significantly increased. No difference in changes in tumor volume was observed between the groups receiving irradiation and the controls. Specific antibody uptake by tumors was always significantly higher than nonspecific having an approximate 4-fold binding advantage. Vascular permeability and the vascular volume of irradiated and control tumors was measured 24 and 72 h after irradiation, using iodine-125-labeled nonspecific antibody and labelling of the red blood cells in vivo with 99mTcO4. At doses higher than 400 cGy, vascular permeability in the tumor 24 h after irradiation was significantly increased (P less than 0.05), while the vascular volume decreased (P less than 0.001) compared to control values. However at 72 h after irradiation there was no difference between treated and control groups. The results obtained in this study suggest a potential value of external irradiation to increase monoclonal antibody uptake by tumors governed mainly by the increased vascular permeability of the tumor vasculature soon after the irradiation exposure.

  5. Downregulation of peroxiredoxin-1 by β-elemene enhances the radiosensitivity of lung adenocarcinoma xenografts. (United States)

    Li, Guoquan; Xie, Bingbing; Li, Xiaolong; Chen, Yinghai; Xu, Yinghui; Xu-Welliver, Meng; Zou, Lijuan


    β-elemene, the active component of elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane), is a naturally occurring compound isolated from the traditional Chinese medicinal herb Curcuma wenyujin. Studies have confirmed that β-elemene enhances the radiosensitivity of lung cancer cell lines such as A549, by multiple pathways; however, their underlying mechanisms and pathways are yet to be elucidated. In the present study, two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry were used to profile the different proteins in A549 cell xenograft models of both treatment groups. The protein/mRNA expression was assessed by reverse transcription-polymerase chain reaction and western blotting techniques in tumor samples from all treatment groups. As a critical player in redox regulation of cancer cells, inhibition of peroxiredoxin-1 (Prx-1) may be an effective option for enhancing the tumor response to radiation. We further verified Prx-1 expression at the transcription and translation levels. β-elemene at a dose of 45 mg/kg had little effect on the Prx-1 protein expression, which was correlated with a moderate antitumor effect. However, a 45 mg/kg dose of β-elemene significantly inhibited the Prx-1 mRNA expression, thereby suggesting a possible influence on the transcriptional process, and radiation significantly increased the Prx-1 mRNA/protein expression compared to the control group (p<0.01). Notably, Prx-1 mRNA/protein expression was significantly lower in the β-elemene/radiation co-treatment group compared to the baseline levels in the control group (p<0.01). These results suggest that radiation-induced Prx-1 expression is directly or indirectly suppressed by β-elemene, thus suggesting a new pathway by which to reverse radioresistance.

  6. Comprehensive analysis of leukocytes, vascularization and matrix metalloproteinases in human menstrual xenograft model.

    Directory of Open Access Journals (Sweden)

    Yong Guo

    Full Text Available In our previous study, menstrual-like changes in mouse were provoked through the pharmacologic withdrawal of progesterone with mifepristone following induction of decidualization. However, mouse is not a natural menstruation animal, and the menstruation model using external stimuli may not truly reflect the occurrence and development of the human menstrual process. Therefore, we established a model of menstruation based on human endometrial xenotransplantation. In this model, human endometrial tissues were transplanted subcutaneously into SCID mice that were ovarectomized and supplemented with estrogen and progestogen by silastic implants with a scheme imitating the endocrinological milieu of human menstrual cycle. Morphology, hormone levels, and expression of vimentin and cytokeratin markers were evaluated to confirm the menstrual-like changes in this model. With 28 days of hormone treatment, transplanted human endometrium survived and underwent proliferation, differentiation and disintegration, similar to human endometrium in vivo. Human CD45+ cells showed a peak of increase 28 days post-transplantation. Three days after progesterone withdrawal, mouse CD45+ cells increased rapidly in number and were significantly greater than human CD45+ cell counts. Mouse CD31+ blood vascular-like structures were detected in both transplanted and host tissues. After progesterone withdrawal, the expression levels of matrix metalloproteinases (MMP 1, 2, and 9 were increased. In summary, we successfully established a human endometrial xenotransplantation model in SCID mice, based on the results of menstrual-like changes in which MMP-1, 2 and 9 are involved. We showed that leukocytes are originated from in situ proliferation in human xenografts and involved in the occurrence of menstruation. This model will help to further understand the occurrence, growth, and differentiation of the endometrium and the underlying mechanisms of menstruation.

  7. In vivo activation of the hypoxia-targeted cytotoxin AQ4N in human tumor xenografts. (United States)

    Williams, Kaye J; Albertella, Mark R; Fitzpatrick, Brian; Loadman, Paul M; Shnyder, Steven D; Chinje, Edwin C; Telfer, Brian A; Dunk, Chris R; Harris, Peter A; Stratford, Ian J


    AQ4N (banoxantrone) is a prodrug that, under hypoxic conditions, is enzymatically converted to a cytotoxic DNA-binding agent, AQ4. Incorporation of AQ4N into conventional chemoradiation protocols therefore targets both oxygenated and hypoxic regions of tumors, and potentially will increase the effectiveness of therapy. This current pharmacodynamic and efficacy study was designed to quantify tumor exposure to AQ4 following treatment with AQ4N, and to relate exposure to outcome of treatment. A single dose of 60 mg/kg AQ4N enhanced the response of RT112 (bladder) and Calu-6 (lung) xenografts to treatment with cisplatin and radiation therapy. AQ4N was also given to separate cohorts of tumor-bearing mice 24 hours before tumor excision for subsequent analysis of metabolite levels. AQ4 was detected by high performance liquid chromatography/mass spectrometry in all treated samples of RT112 and Calu-6 tumors at mean concentrations of 0.23 and 1.07 microg/g, respectively. These concentrations are comparable with those shown to be cytotoxic in vitro. AQ4-related nuclear fluorescence was observed in all treated tumors by confocal microscopy, which correlated with the high performance liquid chromatography/mass spectrometry data. The presence of the hypoxic marker Glut-1 was shown by immunohistochemistry in both Calu-6 tumors and RT112 tumors, and colocalization of AQ4 fluorescence and Glut-1 staining strongly suggested that AQ4N was activated in these putatively hypoxic areas. This is the first demonstration that AQ4N will increase the efficacy of chemoradiotherapy in preclinical models; the intratumoral levels of AQ4 found in this study are comparable with tumor AQ4 levels found in a recent phase I clinical study, which suggests that these levels could be potentially therapeutic.

  8. Improved radioimmunoscintigraphy of human mammary carcinoma xenografts after injection of an anti-antibody

    Energy Technology Data Exchange (ETDEWEB)

    Senekowitsch, R.; Bode, W.; Glaessner, H.; Moellenstaedt, S.; Kriegel, H.; Reidel, G.; Pabst, H.W.


    The low tumor-to-background ratio obtained after administration of radiolabeled whole monoclonal antibodies (MAbs) is one of the major problems in immunoscintigraphy and -therapy. To reduce the blood pool label caused by the circulation of radiolabeled MAb we have investigated the advantage of injecting an anti-antibody after administration of tumor-specific MAb in nude mice bearing human mammary carcinoma xenografts. The MAb MA 10-11 of rat origin, used in these studies, had shown a high affinity to human mammary carcinoma tissue on frozen sections and low cross-reactivity with various normal human tissues. 24 h after injection of 1.5 MBq /sup 131/I-labeled MAb containing 10 IgG/sub 2a/ one group of mice received an additional injection of 100 anti-rat antibody. Blood taken 2 min after the second antibody injection showed nearly the whole activity bound to antibody aggregates, that cleared very rapidly from the circulation and accumulated in liver and spleen. The transitory high liver activity decreased within several hours because of rapid deiodination of the antibody-complex in this organ. The release of radioactivity from the spleen, however, was found to be much slower. The rapid excretion of the radioactivity from the blood pool combined with a nearly constant tumor activity allowed early tumor detection with tumor-to-blood ratios of 250:1 at 48 h after anti-antibody injection compared to 1.1:1 obtained for the control animals. In addition the results may explain the reported reduction of imaging quality and high uptake of radioactivity in the spleen of patients having repeated injections of mouse MAbs due to complex formation after development of human anti-mouse antibodies

  9. Radioimmunoimaging of osteogenic sarcoma xenografts in nude mice using monoclonal antibodies to osteogenic sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Sakahara, H.; Endo, K.; Nakashima, T.; Koizumi, M.; Ohta, H.; Kunimatsu, M.; Torizuka, K.; Nakamura, T.; Tanaka, H.; Kotoura, Y.


    The authors have developed several monoclonal antibodies against human osteogenic sarcoma, one of which; OST7 (IgGl) selectively localized in osteogenic sarcoma xenografts in nude mice. In the present study, F(ab')/sub 2/ fragment was compared with whole IgG and those labeled with In-111 as well as I-131 were used as a radiotracer for the scintigraphic imaging of tumors. IgC and F(ab')/sub 2/ were labeled with I-131 using chloramine-T method and injected into nude mice bearing human osteogenic sarcoma. Scintigrams at day 2 clearly delineated the site of tumors with almost no radioactivity in other organs with F(ab')/sub 2/, which yielded much better images than whole IgG. Tumor-to-blood ratio of 6.09-27.87 was obtained at day 2 using F(ab')/sub 2/, whereas it was 0.76-1.12 at day 2 and 2.05-3.27 at day 7 with IgG. I-131 labeled nonspecific F(ab')/sub 2/ or IgG resulted in no or very low tumor uptake with tumor-to-blood ratio of 0.94-1.18 at day 2 for F(ab')/sub 2/ and 0.67-0.76 at day 7 for IgG, respectively. In-111 labeled F(ab')/sub 2/ fragment of OST7, which was prepared using DTPA as a bifunctional chelate, also showed a high tumor accumulation with tumor-to-blood ratio of 11.67-17.54 at day 2, but higher background activity in the liver and kidney was observed than I-131 labeled one. These results indicate that F(ab')/sub 2/ fragment of OST7 labeled with either I-131 or In-111, has a great potential for the radioimmunoimaging of osteogenic sarcoma.

  10. Patient-derived xenograft mouse models of pseudomyxoma peritonei recapitulate the human inflammatory tumor microenvironment. (United States)

    Kuracha, Murali R; Thomas, Peter; Loggie, Brian W; Govindarajan, Venkatesh


    Pseudomyxoma peritonei (PMP) is a neoplastic syndrome characterized by peritoneal tumor implants with copious mucinous ascites. The standard of care for PMP patients is aggressive cytoreductive surgery performed in conjunction with heated intraperitoneal chemotherapy. Not all patients are candidates for these procedures and a majority of the patients will have recurrent disease. In addition to secreted mucin, inflammation and fibrosis are central to PMP pathogenesis but the molecular processes that regulate tumor-stromal interactions within the peritoneal tumor microenvironment remain largely unknown. This knowledge is critical not only to elucidate PMP pathobiology but also to identify novel targets for therapy. Here, we report the generation of patient-derived xenograft (PDX) mouse models for PMP and assess the ability of these models to replicate the inflammatory peritoneal microenvironment of human PMP patients. PDX mouse models of low- and high-grade PMP were generated and were of a similar histopathology as human PMP. Cytokines previously shown to be elevated in human PMP were also elevated in PDX ascites. Significant differences in IL-6 and IL-8/KC/MIP2 were seen between human and PDX ascites. Interestingly, these cytokines were mostly secreted by mouse-derived, tumor-associated stromal cells rather than by human-derived PMP tumor cells. Our data suggest that the PMP PDX mouse models are especially suited to the study of tumor-stromal interactions that regulate the peritoneal inflammatory environment in PMP as the tumor and stromal cells in these mouse models are of human and murine origins, respectively. These mouse models are therefore, likely to be useful in vivo surrogates for testing and developing novel therapeutic treatment interventions for PMP.

  11. Intervention of Mirtazapine on gemcitabine-induced mild cachexia in nude mice with pancreatic carcinoma xenografts

    Institute of Scientific and Technical Information of China (English)

    Shu-Man Jiang; Jian-Hua Wu; Lin Jia


    AIM:To investigate the effect of Mirtazapine on tumor growth,food intake,body weight,and nutritional status in gemcitabine-induced mild cachexia.METHODS:Fourteen mice with subcutaneous xenografts of a pancreatic cancer cell line (SW1990) were randomly divided into Mirtazapine and control groups.Either Mirtazapine (10 mg/kg) or saline solution was orally fed to the mice every day after tumor implantation.A model of mild cachexia was then established in both groups by intraperitoneal injection of Gemcitabine (50 mg/kg) 10 d,13 d,and 16 d after tumor implantation.Tumor size,food intake,body weight,and nutritional status were measured during the experiment.All mice were sacrificed at day 28.RESULTS:(1) After 7 d of gemcitabine administration,body-weight losses of 5%-7% which suggested mild cachexia were measured; (2) No significant difference in tumor size was detected between the Mirtazapine and control groups (P > 0.05); and (3) During the entire experimental period,food intake and body weight were slightly greater for the Mirtazapine group compared with controls (although these differences were not statistically significant).After 21 d,mice in the Mirtazapine group consumed significantly more food than control mice (3.95 ± 0.14 g vs 3.54 ± 0.10 g,P =0.004).After 25 d,mice in the Mirtazapine group were also significantly heavier than control mice (17.24 ± 0.53 g vs 18.05 ± 0.68 g,P =0.014).CONCLUSION:Mild cachexia model was successfully established by gemcitabine in pancreatic tumor-bearing mice.Mirtazapine can improve gemcitabine-induced mild cachexia in pancreatic tumor-bearing mice.It was believed to provide a potential therapeutic perspective for further studies on cachexia.

  12. Predictive potential of photoacoustic spectroscopy in breast tumor detection based on xenograft serum profiles (United States)

    Priya, Mallika; Chandra, Subhas; Rao, Bola Sadashiva Satish; Ray, Satadru; Mahato, Krishna Kishore


    Breast cancer is the second most common cancer all over the world. Heterogeneity in breast cancer makes it a difficult task to detect with the existing serum markers at an early stage. With an aim to detect the disease early at the pre-malignant level, MCF-7 cells xenografts were developed using female nude mice and blood serum were extracted on days 0th, 10th, 15th & 20th post tumor cells injection (N=12 for each time point). Photoacoustic spectra were recorded on the serum samples at 281nm pulsed laser excitations. A total of 144 time domain spectra were recorded from 48 serum samples belonging to 4 different time points. These spectra were then converted into frequency domain (0-1250kHz) using MATLAB algorithms. Subsequently, seven features (mean, median, mode, variance, standard deviation, area under the curve & spectral residuals after 10th degree polynomial fit) were extracted from them and used for PCA. Further, using the first three Principal components (PCs) of the data, Linear Discriminate Analysis has been carried out. The performance of the analysis showed 82.64% accuracy in predicting various time points under study. Further, frequency-region wise analysis was also performed on the data and found 95 - 203.13 kHz region most suitable for the discrimination among the 4 time points. The analysis provided a clear discrimination in most of the spectral features under study suggesting that the photoacoustic technique has the potential to be a diagnostic tool for early detection of breast tumor development

  13. Endogenous retrovirus induces leukemia in a xenograft mouse model for primary myelofibrosis. (United States)

    Triviai, Ioanna; Ziegler, Marion; Bergholz, Ulla; Oler, Andrew J; Stübig, Thomas; Prassolov, Vladimir; Fehse, Boris; Kozak, Christine A; Kröger, Nicolaus; Stocking, Carol


    The compound immunodeficiencies in nonobese diabetic (NOD) inbred mice homozygous for the Prkdc(scid) and Il2rg(null) alleles (NSG mice) permit engraftment of a wide-range of primary human cells, enabling sophisticated modeling of human disease. In studies designed to define neoplastic stem cells of primary myelofibrosis (PMF), a myeloproliferative neoplasm characterized by profound disruption of the hematopoietic microenvironment, we observed a high frequency of acute myeloid leukemia (AML) in NSG mice. AML was of mouse origin, confined to PMF-xenografted mice, and contained multiple clonal integrations of ecotropic murine leukemia virus (E-MuLV). Significantly, MuLV replication was not only observed in diseased mice, but also in nontreated NSG controls. Furthermore, in addition to the single ecotropic endogenous retrovirus (eERV) located on chromosome 11 (Emv30) in the NOD genome, multiple de novo germ-line eERV integrations were observed in mice from each of four independent NSG mouse colonies. Analysis confirmed that E-MuLV originated from the Emv30 provirus and that recombination events were not necessary for virus replication or AML induction. Pathogenicity is thus likely attributable to PMF-mediated paracrine stimulation of mouse myeloid cells, which serve as targets for retroviral infection and transformation, as evidenced by integration into the Evi1 locus, a hotspot for retroviral-induced myeloid leukemia. This study thus corroborates a role of paracrine stimulation in PMF disease progression, underlines the importance of target cell type and numbers in MuLV-induced disease, and mandates awareness of replicating MuLV in NOD immunodeficient mice, which can significantly influence experimental results and their interpretation.

  14. Effect of Arctium lappa (burdock) extract on canine dermal fibroblasts. (United States)

    Pomari, Elena; Stefanon, Bruno; Colitti, Monica


    Although the biological activities of Arctium lappa (burdock) have been already investigated in human and other species, data evaluating the molecular mechanisms have not been reported in the dog. In this study we analyzed for the first time the effect of a root extract of burdock on molecular responses in canine dermal fibroblasts with H2O2 stimulation (H group), with burdock treatment (B group) and with H2O2 stimulation and burdock treatment (BH group), using RNAseq technology. Differentially expressed genes (P<0.05) of H, B and BH groups in comparison to the untreated sample (negative control, C group) were identified with MeV software and were functional annotated and monitored for signaling pathways and candidate biomarkers using the Ingenuity Pathways Analysis (IPA). The expression profile of canine dermal fibroblasts treated with burdock extract with or without H2O2 stimulation, showed an up-regulation of mitochondrial superoxide dismutase (SOD2), disheveled 3 (DVL3) and chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2). The data suggested that burdock has implications in cell adhesion and gene expression with the modulation of Wnt/β catenin signaling and Chondroitin Sulphate Biosynthesis that are particularly important for the wound healing process.

  15. Behavioral and psychological characteristics of canine victims of abuse. (United States)

    McMillan, Franklin D; Duffy, Deborah L; Zawistowski, Stephen L; Serpell, James A


    Abuse is an intentional act that causes harm to an individual. Dogs (Canis familiaris) with a known or suspected history of abuse were solicited for the study. A panel of 5 experts in canine behavior and abuse selected the dogs judged as having a certain or near certain history of being abused for inclusion in the study. Behavioral evaluations of the dogs were obtained using the Canine Behavioral Assessment and Research Questionnaire, which utilizes ordinal scales to rate either the intensity or frequency of the dog's behaviors. Sixty-nine dogs ultimately met the criteria for inclusion in the study. When compared with a convenience sample of 5,239 companion dogs, abused dogs were reported as displaying significantly higher rates of aggression and fear directed toward unfamiliar humans and dogs, excitability, hyperactivity, attachment and attention-seeking behaviors, persistent barking, and miscellaneous strange or repetitive behaviors. Delineating the behavioral and psychological characteristics of abused dogs provides the first step in identifying and distinguishing the risk factors and sequelae associated with abuse, which may inform the development of preventive and therapeutic programs for nonhuman animal abuse.

  16. Mandibular Canine Transmigration: Report of Three Cases and Literature Review (United States)

    Bhullar, Mandeep K.; Aggarwal, Isha; Verma, Rashmi; Uppal, Amandeep S.


    Aims and Objectives: Transmigration is a rare phenomenon seen almost exclusively in the mandibular canines. The aim of the present study is to review transmigration phenomenon. Materials and Methods: Appropriate guidelines for a systematic review were followed. The time period selected for the present systematic review was 2001–2016. The studies were selected from various electronic databases on the basis of their title, study, design, keywords, and abstracts. A total of 150 citations were searched initially, and after proper screening, 59 relevant articles were included. Additional data was obtained by searching journals and reference lists. Results: The literature search shows that transmigration is more frequent in the mandible than maxilla. The etiology of the condition is obscure; however, multiple factors have been attributed to the condition. They are more readily recognized now with the advent of panoramic radiographs. Transmigration is a rare anomaly causing varied manifestations and requires an interdisciplinary approach for management. Conclusion: Early diagnosis of impacted canines is mandatory for timely treatment to ensure facial harmony and improved function. PMID:28316943

  17. Differential genetic regulation of canine hip dysplasia and osteoarthritis.

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    Zhengkui Zhou

    Full Text Available BACKGROUND: Canine hip dysplasia (HD is a common polygenic trait characterized by hip malformation that results in osteoarthritis (OA. The condition in dogs is very similar to developmental dysplasia of the human hip which also leads to OA. METHODOLOGY/PRINCIPAL FINDINGS: A total of 721 dogs, including both an association and linkage population, were genotyped. The association population included 8 pure breeds (Labrador retriever, Greyhounds, German Shepherd, Newfoundland, Golden retriever, Rottweiler, Border Collie and Bernese Mountain Dog. The linkage population included Labrador retrievers, Greyhounds, and their crosses. Of these, 366 dogs were genotyped at ∼22,000 single nucleotide polymorphism (SNP loci and a targeted screen across 8 chromosomes with ∼3,300 SNPs was performed on 551 dogs (196 dogs were common to both sets. A mixed linear model approach was used to perform an association study on this combined association and linkage population. The study identified 4 susceptibility SNPs associated with HD and 2 SNPs associated with hip OA. CONCLUSION/SIGNIFICANCE: The identified SNPs included those near known genes (PTPRD, PARD3B, and COL15A1 reported to be associated with, or expressed in, OA in humans. This suggested that the canine model could provide a unique opportunity to identify genes underlying natural HD and hip OA, which are common and debilitating conditions in both dogs and humans.

  18. Aquaporin water channels in the canine gubernaculum testis. (United States)

    Arrighi, Silvana; Aralla, Marina; Fracassetti, Paola; Mobasheri, Ali; Cremonesi, Fausto


    The jelly-like gubernaculum testis (GT) is a hydrated structure consisting of a concentric sheath of dense connective tissue around a loose mesenchymal core, with two cords of skeletal muscle cells asymmetrically placed alongside. Expansion of the GT occurs during the transabdominal phase of testicular descent, linked to cell proliferation together with modifications of the hydric content of the organ. The aim of this study was to detect immunohistochemically the presence of aquaporins (AQPs), integral membrane proteins permitting passive transcellular water movement, in the canine GTs. Samples (n=15) were obtained from pregnancies of 9 medium sized bitches and dissected from healthy fetuses. Five fetuses were aged 35-45 days of gestation, 10 fetuses from 46 days of gestation to delivery, thus offering us the opportunity to study the progressive maturation of the gubernacula. The presence of AQP3, 4, 7, 8 and -9 was assessed in the muscular components of the GT, some of them (AQP3, AQP4, AQP7) with increasing intensity through the second half of pregnancy up to term. AQP1 was localized in the capillary and venous endothelia in the younger fetuses, also in the artery adventitia and in the nerve perineurium in progressively older fetuses. These data demonstrate the potential importance and contribution of AQP-mediated water flux in hydration and volume modification of the growing GT in a canine model.

  19. Sphingomyelin induces structural alteration in canine parvovirus capsid. (United States)

    Pakkanen, Kirsi; Karttunen, Jenni; Virtanen, Salla; Vuento, Matti


    One of the essential steps in canine parvovirus (CPV) infection, the release from endosomal vesicles, is dominated by interactions between the virus capsid and the endosomal membranes. In this study, the effect of sphingomyelin and phosphatidyl serine on canine parvovirus capsid and on the phospholipase A(2) (PLA(2)) activity of CPV VP1 unique N-terminus was analyzed. Accordingly, a significant (P< or =0.05) shift of tryptophan fluorescence emission peak was detected at pH 5.5 in the presence of sphingomyelin, whereas at pH 7.4 a similar but minor shift was observed. This effect may relate to the exposure of VP1 N-terminus in acidic pH as well as to interactions between sphingomyelin and CPV. When the phenomenon was further characterized using circular dichroism spectroscopy, differences in CPV capsid CD spectra with and without sphingomyelin and phosphatidyl serine were detected, corresponding to data obtained with tryptophan fluorescence. However, when the enzymatic activity of CPV PLA(2) was tested in the presence of sphingomyelin, no significant effect in the function of the enzyme was detected. Thus, the structural changes observed with spectroscopic techniques appear not to manipulate the activity of CPV PLA(2), and may therefore implicate alternative interactions between CPV capsid and sphingomyelin.

  20. Treatment of canine Old World visceral leishmaniasis: a systematic review. (United States)

    Noli, Chiara; Auxilia, Silvia T


    Canine visceral leishmaniasis is a systemic disease caused by Leishmania infantum. The aim of this systematic review was to identify and evaluate the evidence of efficacy of interventions for treatment or prevention of canine visceral leishmaniasis, and to propose recommendations for or against their use. Forty-seven articles describing clinical trials published between 1980 and 2004 fulfilled selection criteria. The evaluation of clinical trials provided good evidence for recommending the use of meglumine antimoniate at a minimum dosage of 100 mg kg(-1) daily for at least 3-4 weeks, combined with allopurinol in order to obtain a good clinical efficacy and a reduced relapse rate. The evaluation of the articles also provided fair evidence for recommending the use of pentamidine (4 mg kg(-1) twice weekly) and aminosidine (5 mg kg(-1) twice daily) for 3-4 weeks. There was insufficient evidence for recommending the use of allopurinol alone, amphotericin B, buparvaquone, ketoconazole, enrofloxacin, and the combinations of metronidazole with spiramicyn or metronidazole with enrofloxacin. Fair evidence against the use of aminosidine at high dosages (20-80 mg kg(-1) per day) was proposed due to its side effects. Evaluation of articles on repellent measures against sand fly vectors of leishmaniasis provided good evidence for recommending deltamethrin collars and fair evidence for recommending spot-on permethrin.