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You are here: Home / Publications / Bibliographies and Resource Guides / Canine Models in Biomedical Research, 1990-2009  / Oncology  Printer Friendly Page
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Canine Models in Biomedical Research,  1990-2009
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Oncology

Akhtar, N., M.L. Padilla, E.B. Dickerson, H. Steinberg, M. Breen, R. Auerbach, and S.C. Helfand (2004). Interleukin-12 inhibits tumor growth in a novel angiogenesis canine hemangiosarcoma xenograft model. Neoplasia 6(2): 106-116. ISSN: 1522-8002.
Abstract: 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 alphavbeta3 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.
Descriptors: pharmacology, tumor biology, spontaneous tumor, hemangiosarcoma cell line, cancer therapy, basic fibroblast growth factor, antiangiogenic effects.

Aniola, J., S.H. Selman, L. Lilge, R. Keck, and J. Jankun (2003). Spatial distribution of liposome encapsulated tin etiopurpurin dichloride (snet2) in the canine prostate: implications for computer simulation of photodynamic therapy. International Journal of Molecular Medicine 11(3): 287-291. ISSN: 1107-3756.
Abstract: Photodynamic therapy (PDT) is a minimally invasive treatment that can be employed in many human diseases including prostate cancer. PDT for prostate cancer depends on the sequestration of a photosensitizing drug within the glandular tissue. The photosensitizer is subsequently activated by light (usually from a laser) and the active drug destroys tissue. Since prostate cancer is a multifocal disease, PDT must ablate the glandular prostate completely. This will depend on the precise placement of light sources in the prostate and delivery of a therapeutic light dose to the entire gland. Also, sources of light and their spatial distribution must be tailored to each individual patient. The uniform, therapeutic light distribution can be achieved by interstitial light irradiation. In this case, the light is delivered by diffusers placed within the substance of the prostate parallel to the urethra at a distance optimized to deliver adequate levels of light and to create the desired photodynamic effect. To help achieve the uniform light distribution throughout the prostate we have developed a computer program that can determine treatment effects. The program predicts the best set of parameters and the position of light diffusers in space, and displays them in graphical or in numerical form assuming a fixed attenuation coefficient. The two parameters of greatest importance in the computer simulation are attenuation coefficient and critical fluence. Both depend on the concentration of active drug within the prostate gland. It is necessary to know the nature of the spatial distribution of photosensitizer within the prostate to execute computer modeling of PDT with high precision. We found that the concentration of SnET2 is heterogeneous in nature, and is higher in the proximity of the glandular capsule. It is clear therefore that any future attempts of computerized modeling of this procedure must take into consideration the uneven sequestration of photosensitizer and the consequential asymmetrical necrosis of the prostate.
Descriptors: models and simulations, computational biology, radiation biology, reproductive system, reproduction, tumor biology, prostate cancer, neoplastic disease, reproductive system disease, male, urologic disease, radiotherapy, photodynamic therapy, clinical techniques, therapeutic and prophylactic techniques, computer simulation.

Boonsoda, S. and P. Wanikiat (2008). Possible role of cyclooxygenase-2 inhibitors as anticancer agents. Veterinary Record 162(5): 159-61. ISSN: 0042-4900.
NAL Call Number: 41.8 V641
Descriptors: cyclooxygenase 2 metabolism, cyclooxygenase 2 inhibitors therapeutic use, neoplasms drug therapy, neoplasms metabolism, cyclooxygenase 2 genetics, dogs, gene expression regulation, neoplastic, models, animal.

Breen, M. (2008). Canine cytogenetics: from band to basepair. Cytogenetic and Genome Research 120(1-2): 50-60. ISSN: 1424-8581.
NAL Call Number: QH431 .C95
Abstract: 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. Copyright 2008 S. Karger AG, Basel.
Descriptors: genetic disorders, cancer, animal models, canine genome, chromosomal location, gene sequence

Cooley, D.M., D.L. Schlittler, L.T. Glickman, M. Hayek, and D.J. Waters (2003). Exceptional longevity in pet dogs is accompanied by cancer resistance and delayed onset of major diseases. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 58(12): B1078-84. ISSN: 1079-5006.
Abstract: To characterize extreme aged pet dogs as a first step in developing an animal model of exceptional longevity, we constructed lifetime medical histories for 345 Rottweiler dogs using information collected from owners and veterinarians. Extreme aged dogs (alive at the 95th percentile age at death for the study population, > or =13.3 years) were compared with a usual longevity group (9-10 years). Exceptional longevity in Rottweiler dogs was accompanied by a significant delay in the onset of major life-threatening diseases; 76% of extreme aged dogs remained free of all major diseases during the first 9 years of life. Only 19% of extreme aged dogs died of cancer versus 82% of dogs with usual longevity (p <.0001). The reduction in cancer mortality in oldest-old pet dogs mimics that seen in human centenarians and provides strong rationale for using this animal model to study comparative mechanisms of cancer resistance in the extreme aged.
Descriptors: animal model, longevity, aging, medical history, cancer resistance.

De Vico, G. and P. Mairolino (2008). Canine and Feline Models for Cancer. M. Conn Sourcebook of Models for Biomedical Research, Humana Press: Totowa, N.J.: London: Springer, p. 677-682.
NAL Call Number: R853.A53 S68 2008
Descriptors: cat, dogs, animal models, canine non-Hodgkins lymphoma, oral malignant melanoma, osteosarcomas, tumor development.

Eisenschenk, A., C. Witzel, M. Lautenbach, A. Ekkernkamp, U. Weber, and M.V. Kuntscher (2007). Does chemotherapy impair the bone healing and biomechanical stability of vascularized rib and fibula grafts? Journal of Reconstructive Microsurgery 23(1): 35-40. ISSN: 0743-684X.
Abstract: The purpose of this study was to observe the impact of chemotherapy on the healing and biomechanical properties of vascularized bone grafts. Ten male beagle dogs were divided into two experimental groups: a chemotherapy group (CH) and control group (C). Group CH received adjuvant and neo-adjuvant chemotherapy. Each animal of both groups underwent the following operative procedures. The 5th and 7th rib were removed and replaced by vascularized pedicle transfers of the adjacent 4th and 8th rib. Additionally, a free fibular flap was elevated and retransferred to the same anatomic position. The rate of bony union on plain x-ray was 100 percent in group C, 30 percent in the vascularized rib, and 80 percent in the fibula grafts of group CH. Microangiography demonstrated no avascular bone segments in group C and in the fibula flaps of group CH. The vascularized ribs of group CH presented with 20 percent avascular bone segments. Biomechanical tests focusing on the durability of the vascularized grafts against bending and torsion forces demonstrated a reduction of the average maximum bending times by 17 percent and 23.9 percent compared to the controls ( P < 0.05). The twisting times were reduced by 13.8 percent (n.s.) and 32.5 percent ( P < 0.05). The data demonstrated a clear worsening in bone healing and stability after simulated adjuvant and neo-adjuvant chemotherapy. Thus, a large animal model was established for the further determination of the effects of chemotherapy on different vascularized bone transfers.
Descriptors: antineoplastic agents pharmacology, bone transplantation pathology, bone and bones drug effects, angiography, antibiotics, antineoplastic pharmacology, antimetabolites, antineoplastic pharmacology, biomechanics, chemotherapy, adjuvant, dogs, doxorubicin pharmacology, fibula, methotrexate pharmacology, microradiography, models, animal, neoadjuvant therapy, pliability, ribs, torque, wound healing drug effects.

Ensminger, W., J. Knol, S. Deremer, E. Wilkinson, S. Walker, D. Williams, and J. Maybaum (2004). Effects of dexamethasone or celecoxib on biliary toxicity after hepatic arterial infusion of 5-fluorodeoxyuridine in a canine model. Cancer Research 64(1): 311-315. ISSN: 0008-5472.
NAL Call Number: 448.8 C16
Abstract: Previous work has shown that in humans the dose-limiting toxicity for fluorodeoxyuridine (2-fluoro-5'-deoxyuridine (FdUrd)) when administered by hepatic arterial infusion is biliary sclerosis. The current study was undertaken to attempt to modify this toxicity in a canine model that has been demonstrated to closely mimic the clinical situation. Unlike previous studies using this model, in which animals were sacrificed after extensive fibrosis had already occurred, the current experiments were designed so that observations of pathology were made at an earlier time, when the initial inflammatory injury underlying the fibrotic process was still taking place. Implantable pumps were used to deliver FdUrd into the hepatic artery of animals at a rate of 0.3 mg/kg/day in the presence or absence of 10 mg/week dexamethasone or 100 mg/day of celecoxib for 35 days, at which time the animals were beginning to show signs of toxicity. After evaluation for radiological evidence of biliary obstruction, the animals were sacrificed and portions of their livers were processed for examination of microscopic pathology and 2-bromo-5'deoxyuridine labeling index. Dexamethasone treatment protected the animals from biliary sclerosis determined radiologically, further validating this model as being representative of the response in humans. Similarly the Cox-2 inhibitor, celecoxib, appeared to provide protection against radiological changes of biliary stricture, although possibly to a lesser degree than the resultant from dexamethasone. In addition, FdUrd treatment caused elevation of the DNA 2-bromo-5'deoxyuridine labeling index above control levels in biliary epithelial cells. Dexamethasone and celecoxib each significantly attenuated the FdUrd-induced elevation of DNA labeling index in biliary epithelium. These findings demonstrate the usefulness of this canine model for studying the mechanisms of drug-induced biliary sclerosis and reinforce the hypothesis that blocking inflammation may retard the progression of injury that eventually leads to fibrosis. This study suggests that clinical testing of celecoxib as a preventive for hepatic arterial-FdUrd induced biliary damage could prove valuable.
Descriptors: digestive system, ingestion and assimilation, pharmacology, veterinary medicine, medical sciences, biliary obstruction, digestive system disease, biliary sclerosis, drug induced, colorectal cancer, neoplastic disease, infusaid model 400 implantable pump, drug delivery device.

Erdelyi, I., D.H.M. Nieskens, J.E. Van Dijk, L. Vass, and H. Nederbragt (2003). Immunohistochemical evaluation of versican, in relation to chondroitin sulphate, in canine mammary tumours. Histology and Histopathology 18(4): 1067-1080. ISSN: 0213-3911.
Abstract: The expression of increased amounts of versican, a chondroitin sulphate proteoglycan, in neoplastic tissues may play a role in promoting tumour cell proliferation and migration. This study investigated the immunolocalization of versican in normal and neoplastic canine mammary tissues, using antibodies 12C5 and 2B1, against different epitopes of the protein core of versican. Antibody CS56, recognising chondroitin sulphate (CS), was used to investigate the relation between versican and CS, which accumulates in canine mammary tumours. We found enhanced versican expression in both benign and malignant tumours, appearing in three main patterns: in periductal tissues, probably in association with basement membranes of ducts; in peripheral invasive areas of malignant tumours; and in spindle cell proliferations and myxoid areas of complex and mixed tumours. The 12C5 and 2B1 immunoreactivities co-localised in all types of tumours, and could be improved by chondroitinase digestion. The only exception was the abundant extracellular matrix (ECM) of spindle cell proliferations, particularly in myxoid areas of complex and mixed tumours, which displayed intense and diffuse 12C5 immunoreactivity and patchy or absent 2B1 and CS56 immunoreactivities; versican immunoreactivity could not be enhanced by chondroitinase digestion. The results indicate that versican is one of the extracellular matrix components characteristic of canine mammary tumours. It appears likely that in complex and mixed tumours versican exists in at least two forms, one of them lacking the CS attachment domain and the 2B1 epitope. Furthermore, the enhanced versican expression in the invasive areas of malignant tumours indicates the involvement of this proteoglycan in tumour cell invasion.
Descriptors: tumor biology, mammary tumor, neoplastic disease, reproductive system disease, female, immunohistochemistry, immunologic techniques, laboratory techniques.

Hemminki, A., A. Kanerva, E.J. Kremer, G.J. Bauerschmitz, B.F. Smith, B. Liu, M. Wang, R.A. Desmond, A. Keriel, B. Barnett, H.J. Baker, G.P. Siegal, and D.T. Curiel (2003). A canine conditionally replicating adenovirus for evaluating oncolytic virotherapy in a syngeneic animal model. Molecular Therapy 7(2): 163-73. ISSN: 1525-0016.
NAL Call Number: RB155.8
Abstract: Oncolytic adenoviruses, which selectively replicate in and subsequently kill cancer cells, have emerged as a promising approach for treatment of tumors resistant to other modalities. Although preclinical results have been exciting, single-agent clinical efficacy has been less impressive heretofore. The immunogenicity of adenoviruses, and consequent premature abrogation of replication, may have been a partial reason. Improving the oncolytic potency of agents has been hampered by the inability to study host-vector interactions in immune-competent systems, since human serotype adenoviruses do not productively replicate in animal tissues. Therefore, approaches such as immunomodulation, which could result in sustained replication and subsequently increased oncolysis, have not been studied. Utilizing the osteocalcin promoter for restricting the replication of a canine adenovirus to dog osteosarcoma cells, we generated and tested the first nonhuman oncolytic adenovirus. This virus effectively killed canine osteosarcoma cells in vitro and yielded a therapeutic benefit in vivo. Canine osteosarcoma is the most frequent malignant disease in large dogs, with over 8000 cases in the United States annually, and there is no curative treatment. Therefore, immunomodulation for increased oncolytic potency could be studied with clinical trials in this population. This could eventually translate into human trials.
Descriptors: animal model, immunomodulation, canine osterosarcoma,oncolytic adenoviruses, in vitro, therapy, in vivo.

Higginbotham, M., C. Henry, K. Katti, S. Casteel, P. Dowling, and N. Pillarsetty (2003). Preclinical tolerance and pharmacokinetic assessment of MU-Gold, a novel chemotherapeutic agent, in laboratory dogs. Veterinary Therapeutics: Research in Applied Veterinary Medicine 4(1): 76-82. ISSN: 1528-3593.
NAL Call Number: SF601 .V4745
Descriptors: dogs, gold, chemotherapy, pharmacokinetics, toxicity

Jahan Parwar, B., D.K. Chhetri, S. Hart, S. Bhuta, and G.S. Berke (2003). Development of a canine model for recurrent respiratory papillomatosis. Annals of Otology Rhinology and Laryngology 112(12): 1011-1013. ISSN: 0003-4894.
Abstract: A canine model for recurrent respiratory papillomatosis (RRP) was developed with canine oral papillomavirus (COPV) inoculated into the buccal mucosa and supraglottic larynx of 5 beagles. The animals received systemic immunosuppression with daily oral prednisone at doses of 0, 1, 2, 3, and 4 mg/kg. Buccal papillomata developed at 6 weeks in all animals and regressed by 10 weeks in the animals that received 0 and 1 mg/kg. The other animals had continuous growth of their buccal papillomata for 26 weeks. The animal that received 2 mg/kg developed papillomata on the lingual surface of the epiglottis that continued to grow through 26 weeks. Systemic oral prednisone successfully maintained COPV-induced oral and laryngeal papillomata in beagles. Thus, COPV-induced oral and laryngeal papillomata that are prednisone-maintained may have utility as a model for RRP.
Descriptors: oncology, human medicine, medical sciences, otolaryngology, human medicine, medical sciences, pulmonary medicine, human medicine, medical sciences, recurrent respiratory papillomatosis, neoplastic disease, respiratory system disease.

Kaewsakhorn, T., M. Gower, W. Kisseberth, C. Capen, M. Calverley, and N. Inpanbutr (2004). Effects of calcitriol and medium chain triglyceride (mct) on cell growth of the canine transitional cell carcinoma of the urinary bladder (tcc) in vitro. FASEB Journal 18(4-5): Abst. 68.8. ISSN: 0892-6638.
Online: http://www.fasebj.org/
NAL Call Number: QH301.F3
Descriptors: calcitriol , cell biology, cell proliferation, pharmacology, tumor biology, bladder transitional cell carcinoma, neoplastic disease, urologic disease, therapy, western blot, genetic techniques, laboratory techniques, drug regimen.

Kangasniemi, M., R.J. Stafford, R.E. Price, E.F. Jackson, and J.D. Hazle (2003). Dynamic gadolinium uptake in thermally treated canine brain tissue and experimental cerebral tumors. Investigative Radiology 38(2): 102-107. ISSN: 0020-9996.
Abstract: RATIONALE AND OBJECTIVES: Thermal coagulation of cerebral tumors induces reactive changes within adjacent brain tissue, which appear as Gd-DTPA enhancement in MR images. This makes assessment of therapeutic success difficult to establish radiographically because the reactive changes can mimic residual tumor. Dynamic Gd-DTPA uptake curves in reactive tissue and tumor were investigated to assess the utility of contrast enhanced (CE)-dynamic MRI to distinguish reactive changes from residual tumor in a canine model. MATERIALS AND METHODS: Cerebral thermal necrosis was induced using a 980 nm laser in 11 dogs with intracerebral transmissible venereal tumors (TVTs). A fast spin-echo T1-weighted imaging sequence was used for CE-dynamic MRI. Gd-DTPA uptake data were acquired with 10-second temporal resolution and for untreated TVTs for reactive tissue using a sigmoidal-exponential model. RESULTS: Characteristic gadolinium uptake curves were measured and characterized for reactive brain tissue, and untreated and treated TVTs. Both early and delayed dynamic responses were significantly different in reactive brain tissue compared with TVT. CONCLUSION: Reactive thermal changes in otherwise normal brain tissue can be distinguished from residual tumor after cerebral thermal therapy using CE -dynamic MRI.
Descriptors: nervous system, neural coordination, pharmacology, tumor biology, cerebral thermal necrosis, nervous system disease, intracerebral transmissible venereal tumor, neoplastic disease, radiotherapy, contrast enhanced dynamic magnetic resonance imaging, clinical techniques, diagnostic techniques, imaging and microscopy techniques, fast spin echo t1 weighted imaging, sigmoidal exponential model, mathematical and computer techniques, thermal coagulation therapy, therapeutic and prophylactic techniques, reactive thermal change.

Kent, M.S., B.R. Madewell, G. Dank, R. Dick, S.D. Merajver, and G.J. Brewer (2004). An anticopper antiangiogenic approach for advanced cancer in spontaneously occurring tumors using tetrathiomolybdate: a pilot study in a canine animal model. Journal of Trace Elements in Experimental Medicine 17(1): 9-20. ISSN: 0896-548X.
NAL Call Number: QP534.J68
Abstract: In this pilot study, 13 dogs of various breeds and ages with a variety of advanced tumors were treated with the antiangiogenic copper complexing drug tetrathiomolybdate. Dose escalations were performed to determine the safe and effective dose in dogs. The study was designed to last for a 6-month period for each dog entered. Dogs were examined weekly for the first 3 months and then every other week for the next 3 months. Complete blood count, serum biochemistry panel, and measurement of serum ceruloplasmin (Cp) content were conducted at each visit to monitor response to drug administration. Serum Cp was used as a surrogate marker of copper status. The owner reported toxicity at each visit. The dog was examined for physical abnormalities. Tumor measurements were completed every 2 weeks using direct measurements of the tumor with calipers in three planes or by direct measurements of the tumor using radiographic or ultrasonographic images in two planes. Tumor response was evaluated only after dogs achieved a 4-week reduction in their serum Cp content. Tumor responses were defined as either disease stabilization or reduction in tumor volume. Nine dogs achieved Cp reduction. Of those dogs, five had no response to treatment, whereas four dogs had tumor responses after Cp reduction, characterized as either disease stabilization or reduction in tumor volume, for the remainder of the study period. There was only mild self-limiting toxicity with use of the drug.
Descriptors: pharmacology, veterinary medicine, medical sciences, advanced cancer, neoplasms, neoplastic disease, drug therapy, spontaneously occurring tumor.

Lee, J.L., C.J. Chang, S.Y. Wu, D.R. Sargan, and C.T. Lin (2004). Secreted frizzled-related protein 2 (SFRP2) is highly expressed in canine mammary gland tumors but not in normal mammary glands. Breast Cancer Research and Treatment 84(2): 139-49. ISSN: 0167-6806.
Abstract: Canine mammary gland tumor (MGT) is the commonest tumor in female dogs and a good animal model of human breast cancer. A group of newly identified genes encoding secreted frizzled-related proteins (SFRP) have been implicated in apoptosis regulation and tumorigenesis. Canine mammary tissues from 50 spontaneous MGTs and 10 normal mammary glands (MGs) were obtained from surgically excised specimens and analyzed for expression of SFRP2, beta-catenin, and cyclin D1. By RT-PCR and in situ hybridization, SFRP2 gene was found abundantly expressed in neoplastic mammary tissues but not in normal mammary tissues, suggesting that SFRP2 may contribute as a tumor marker in canine MGTs. By immunohistochemical staining, the immunoreactivity of the SFRP2 protein was detected in more diverse areas than SFRP2 mRNA expression, including nuclei or/and cytoplasm and extracellular matrix of the tumor. In tumor masses, beta-catenin lost its tight association with the membrane and diffused into the nucleus. The expression of beta-catenin (79.4% positive) and cyclin D1 (71.4% positive) was also increased in MGTs. In the course of tumor progression, SFRP2 mRNA ( p < 0.05) and beta-catenin protein ( p < 0.01) steadily increased but not in cyclin D1. The level of SFRP2 was linearly correlated with its downstream target beta-catenin ( p < 0.05), but not correlated with cyclin D1 ( p < 0.5). As revealed in this study, the exclusive overexpression of SFRP2 in canine MGTs suggests that SFRP2 is a potential candidate gene for further investigation of mammary tumorigenesis and complex etiology of the canine model of mammary neoplasms.
Descriptors: animal model, female, breast cancer, secreted frizzled-related proteins (SFRP), apotosis regulation, tumorigenesis.

Lee, J.L., C.J. Chang, L.L. Chueh, and C.T. Lin (2003). Expression of secreted frizzled-related protein 2 in a primary canine mammary tumor cell line: a candidate tumor marker for mammary tumor cells. In Vitro Cellular and Developmental Biology Animal 39(5-6): 221-227. ISSN: 1071-2690.
NAL Call Number: QH585.A1I58
Abstract: Canine mammary tumors (CMTs) have been proposed to be a good animal model for human breast cancer. To provide a basis for the tumorigenic study of CMTs, cell lines were established using a modified cell culture technique. The epithelial morphology and immunostaining with cytokeratin 18 confirmed the epithelial origin of the cells. In an investigation of possible mammary tumorigenesis-related factors, the expression of Wnt signaling-related proteins was detected in cell lines. Secreted frizzled-related protein 2 (SFRP2) was abundantly expressed in CMT cells but not in normal canine mammary gland (MG) cells. Secreted frizzled-related protein 2 was secreted into the culture medium and was associated with the extracellular matrix. In addition, increased expressions of beta-catenin and cyclin D1 were observed in cells overexpressing SFRP2. The marked differential expression of SFRP2 reveals that this protein may be a potential candidate marker for CMTs. The CMT cell line established in this study provides a useful tool and experimental model for understanding both the tumorigenesis of CMTs and the role of Wnt signaling in cancers.
Descriptors: biochemistry and molecular biophysics, cell biology, reproductive system, reproduction, tumor biology, mammary tumor, neoplastic disease, pathology, immunostaining, immunologic techniques, laboratory techniques, primary culture, culturing techniques, wnt signaling, epithelial morphology, mammary tumorigenesis, animal model, breast cancer, canine mammary tumors, Secreted frizzled-related protein 2 (SFRP2).

Lilge, L., N. Pomerleau Dalcourt, A. Douplik, S.H. Selman, R.W. Keck, M. Szkudlarek, M. Pestka, and J. Jankun (2004). Transperineal in vivo fluence-rate dosimetry in the canine prostate during snet2-mediated pdt. Physics in Medicine and Biology 49(14): 3209-3225. ISSN: 0031-9155.
Abstract: Advances in photodynamic therapy (PDT) treatment for prostate cancer can be achieved either by improving selectivity of the photosensitizer towards prostate gland tissue or improving the dosimetry by means of individualized treatment planning using currently available photosensitizers. The latter approach requires the ability to measure, among other parameters, the fluence rate at different positions within the prostate and the ability to derive the tissue optical properties. Here fibre optic probes are presented capable of measuring the fluence rate throughout large tissue volumes and a method to derive the tissue optical properties for different volumes of the prostate. The responsivity of the sensors is sufficient to detect a fluence rate of 0.1 mW cm-2. The effective attenuation coefficient in the canine prostate at 660 nm is higher at the capsule (2.15 +/- 0.19 cm-1) than in proximity of the urethra (1.84 +/- 0.36 cm-1). Significant spatial and temporal intra- and inter-canine variability in the tissue optical properties was noted, highlighting the need for individualized monitoring of the fluence rate for improved dosimetry.
Descriptors: computational biology, reproductive system, reproduction, tumor biology, prostate cancer, neoplastic disease, reproductive system disease, male, urologic disease, photodynamic therapy, clinical techniques, therapeutic and prophylactic techniques, transperineal in vivo fluence rate dosimetry, laboratory techniques, attenuation coefficient, fluence rate, inter canine variability, intra canine variability, tissue optical properties.

Marsella, R. and C.F. Nicklin (2000). Double-blinded cross-over study on the efficacy of pentoxifylline for canine atopy. Veterinary Dermatology 11(4): 255-260. ISSN: 0959-4493.
NAL Call Number: SF901.V47
Abstract: The pathogenesis of canine atopy has not been established completely. Recent studies have shown that tumour necrosis factor alpha and Interleukin-6 play a role in allergic reactions in humans and mice. Pentoxifylline (PTX) suppresses synthesis of these cytokines and may be a useful therapy for modulating the symptoms of canine atopy. The objectives of this study were to investigate the effects of PTX (10 mg kg-1 twice daily for 4 weeks) on clinical signs (erythema and pruritus) and intradermal skin test reactivity in 10 atopic dogs. The study was a double-blinded, placebo controlled, crossover clinical trial with a washout period of 2 weeks between treatments. Clinical signs were evaluated and scored by the investigator and owners. During PTX treatment, scores of pruritus and erythema decreased significantly. PTX did not affect intradermal skin test reactivity to house dust mites after 15 min.
Descriptors: atopy, pentoxifylline, hypersensitivity, tumour necrosis factor, interleukin 6, cytokines.
Language of Text: , LS=German; Spanish; French.

Mirsalis, J.C., J. Schindler Horvat, J.R. Hill, C.E. Green, C. Mitoma, J.E. Tomaszewski, C.A. Tyson, and S.J. Donohue (2003). Toxicity of a quinocarmycin analog, dx-52-1, in rats and dogs in relation to clinical outcome. Cancer Chemotherapy and Pharmacology 51(3): 193-201. ISSN: 0344-5704.
NAL Call Number: RC271.C5C28
Abstract: Purpose: Quinocarmycin analog DX-52-1 is a cyanated derivative of quinocarmycin, a compound isolated from cultures of Streptomyces melanovinaceus. DX-52-1 was selected for preclinical development because it showed efficacy against melanoma cell lines in the NCI human tumor cell screen and melanoma xenografts in mice. This report describes studies in rats and dogs to determine the maximum tolerated dose (MTD) and identify dose-limiting toxicities (DLT) in each species in different regimens to establish a safe starting dose and potential target organs of DX-52-1 for phase I clinical trials. Methods: DX-52-1 was administered to Fischer 344 rats using repeated intravenous (i.v.) slow bolus injections following q3hX3 and q3hX3,q7dX3 regimens, and to beagle dogs using a single injection, 6-h continuous i.v. infusion (c.i.v.) and weekly 6-h c.i.v. for 3 weeks. Endpoints evaluated included clinical observations, body weights, hematology, serum clinical chemistry, and microscopic pathology of tissues. Results: The MTD of DX-52-1 was a total dose of 18 mg/m2 body surface area for q3hX3 administration in rats and 30 mg/m2 for a single c.i.v. administration in dogs. The total dose MTD for rats on a weekly (q3hX3,q7dX3) regimen was 54 mg/m2, and for dogs on the weekly X3 (6-h c.i.v.) infusion was 60 mg/m2. In rats, significant elevations in blood urea nitrogen and creatinine were observed together with acute renal tubular necrosis histologically. Modest increases in liver enzymes were also observed, as were decreases in reticulocytes that were unaccompanied by histologic changes in liver and bone marrow. In dogs, adverse signs included vomiting/retching, diarrhea, and transient hypothermia; also red blood cells, hemoglobin, hematocrit, and lymphocytes were decreased. Histologic evaluation of tissues from dogs revealed necrosis and cellular depletion of the bone marrow, and extensive damage to the entire gastrointestinal tract, including marked cellular necrosis of the mucosa and lymphoid necrosis of the gastrointestinal associated lymphoid tissue. Destruction of the mucosal lining of the intestinal tract was likely responsible for dehydration, toxemia, septicemia, and shock seen in moribund dogs. Conclusions: The MTD values were comparable between rats and dogs given roughly similar dose regimens (single dose or weekly) and both species tolerated a higher total dose with weekly administration. However, the principal target organ responsible for DLT in rats was the kidney, whereas in dogs, the most severe effects were on the gastrointestinal tract and bone marrow. Both renal and gastrointestinal toxicities were reported in patients after 6-h c.i.v. infusions in a limited phase I clinical trial, indicating that neither animal model alone was predictive of DX-52-1-induced toxicity in humans, and that both species were required to define human toxicity.
Descriptors: animal models, rats, dogs, human, cancer therapy, melanoma, toxicity studies, preclinical development, Quinocarmycin analog DX-52-1, efficacy pharmacology, toxicology, bone marrow toxicity, blood and lymphatic disease, gastrointestinal toxicity, digestive system disease, renal toxicity, toxicity, urologic disease, histopathology, histology and cytology techniques, laboratory techniques, body weight, species differences.

Modiano, J.F., S.P. Fosmire, S.R. Bianco, R. Thomas, M. Breen, D.M. Getzy, J. Wojcieszyn, and S.C. Helfand (2003). Differential phosphorylation of rb in canine b and t cell lymphomas. FASEB Journal 17(7): C324-C325. ISSN: 0892-6638.
NAL Call Number: QH301.F3
Descriptors: tumor biology, B cell lymphoma, blood and lymphatic disease, immune system disease, neoplastic disease, T cell lymphoma, blood and lymphatic disease, neoplastic disease, immunohistology, immunologic techniques, laboratory techniques.

Moore, R.B., Z. Xiao, R.J. Owen, R. Ashforth, D. Dickey, C. Helps, and J. Tulip (2008). Photodynamic therapy of the canine prostate: intra-arterial drug delivery. Cardiovascular and Interventional Radiology 31(1): 164-76.
NAL Call Number: RC683.5.R3
Abstract: PURPOSE: Interstitial photodynamic therapy (PDT) selectively destroys tissue targeted with a photosensitizer and then exposed to light of a specific wavelength. We report a novel delivery method--intra-arterial drug delivery for PDT of the prostate--in a canine model. METHODS: To evaluate drug distribution, the prostatovesical artery was selectively cannulated and photosensitizers alone or in conjunction with 99m-technetium-labeled macro-aggregated albumin ((99m)Tc-MAA) were injected via a 3 Fr microcatheter in 8 animals. One dog was followed for 3 months to determine tolerance and toxicity. The remaining animals were euthanized and imaged with whole-body single photon emission CT and gamma counting for radioactivity distribution. Photosensitizer distribution was further analyzed by fluorescence confocal microscopy and tissue chemical extraction. To evaluate PDT, the photosensitizer QLT0074 was infused in 3 animals followed by interstitial illumination with 690 nm laser light. RESULTS: Intra-arterial infusion selectively delivered drugs to the prostate, with both radioactivity and photosensitizer levels significantly higher (up to 18 times) than in the surrounding organs (i.e., rectum). With unilateral injection of (99m)Tc-MAA, only the injected half of the prostate showed activity whereas bilateral administration resulted in drug delivery to the entire prostate. PDT resulted in comprehensive damage to the prostate without severe complications or systemic toxicity. CONCLUSION: Injection of radiolabeled MAA into the prostatovesical artery results in distribution within the prostate with negligible amounts reaching the adjacent organs. PDT also demonstrates selective damage to the prostate, which warrants clinical application in targeted prostate therapies.
Descriptors: photochemotherapy methods, prostate drug effects, radiopharmaceuticals administration and dosage, technetium tc 99m aggregated albumin administration and dosage, dogs, fluoroscopy, follow up studies, indoles administration and dosage, indoles metabolism, indoles pharmacokinetics, infusions, intra arterial, microscopy, confocal methods, models, animal, organometallic compounds administration and dosage, organometallic compounds metabolism, organometallic compounds pharmacokinetics, photochemotherapy adverse effects, photosensitizing agents administration and dosage, photosensitizing agents metabolism, photosensitizing agents pharmacokinetics, porphyrins administration and dosage, porphyrins metabolism, prostate metabolism, prostate radiography, radiopharmaceuticals adverse effects, radiopharmaceuticals pharmacokinetics, technetium tc 99m aggregated albumin adverse effects, technetium tc 99m aggregated albumin pharmacokinetics, tissue distribution, tomography, emission computed, single photon.

Ong, A.M., L.M. Su, I. Varkarakis, T. Inagaki, R.E. Link, S.B. Bhayani, A. Patriciu, B. Crain, and P.C. Walsh (2004). Nerve sparing radical prostatectomy: effects of hemostatic energy sources on the recovery of cavernous nerve function in a canine model. Journal of Urology 171(4 Supplement): 284. ISSN: 0022-5347.
NAL Call Number: 448.8 J8234
Descriptors: methods and techniques, reproductive system, reproduction, bipolar electrosurgery, experimental surgical techniques, laboratory techniques, nerve sparing radical prostatectomy, cavernous nerve function, erectile function, hemostatic energy source, peak intracavernous pressure.

Pinho, S.S., A.J. Matos, C. Lopes, N.T. Marcos, J. Carvalheira, C.A. Reis, and F. Gartner (2007). Sialyl Lewis x expression in canine malignant mammary tumours: correlation with clinicopathological features and E-Cadherin expression. BMC Cancer 7: 124.
Abstract: BACKGROUND: Sialyl Lewis x (sLex) antigen is a carbohydrate antigen that is considered not only a marker for cancer but also implicated functionally in the malignant behaviour of cancer cells. Overexpression of sLex is associated with enhanced progression and metastases of many types of cancer including those of the mammary gland. Canine mammary tumours can invade and give rise to metastases via either lymphatic or blood vessels.E-Cadherin is specifically involved in epithelial cell-to-cell adhesion. In cancer, E-Cadherin underexpression is one of the alterations that characterizes the invasive phenotype and is considered an invasion/tumour suppressor gene. Partial or complete loss of E-Cadherin expression correlates with poor prognosis in canine malignant mammary cancer.The aim of this study was to analyse the sLex expression in canine malignant mammary tumours and to evaluate if the presence of sLex correlates with the expression of E-Cadherin and with clinicopathological features. METHODS: Fifty-three cases of canine mammary carcinomas were analysed immunohistochemically using monoclonal antibodies against sLex (IgM) and E-Cadherin (IgG). The clinicopathological data were then assessed to determine whether there was a correlation with sLex tumour expression. Double labelled immunofluorescence staining was performed to analyse the combined expression of sLex and E-Cadherin. RESULTS: sLex expression was consistently demonstrated in all cases of canine mammary carcinomas with different levels of expression. We found a significant relationship between the levels of sLex expression and the presence of lymph node metastases. We also demonstrated that when E-Cadherin expression was increased sLex was reduced and vice-versa. The combined analysis of both adhesion molecules revealed an inverse relationship. CONCLUSION: In the present study we demonstrate the importance of sLex in the malignant phenotype of canine malignant mammary tumours. Our results support the use of sLex as a prognostic tumour marker in canine mammary carcinomas. Furthermore, we showed that sLex and E-Cadherin expression were inversely correlated. Future studies are warranted to clarify the molecular mechanism underlying the relation between sLex and E-Cadherin in canine mammary carcinoma cells which represents an important comparative model to woman breast cancer.
Descriptors: cadherins metabolism, mammary neoplasms, animal metabolism, mammary neoplasms, animal pathology, neoplasm invasiveness pathology, oligosaccharides metabolism, tumor markers, biological analysis, biopsy, needle, cadherins genetics, cell transformation, neoplastic pathology, dogs, gene expression regulation, neoplastic, immunohistochemistry, mammary neoplasms, animal genetics, models, animal, neoplasm staging, oligosaccharides genetics, probability, random allocation, reference values, sensitivity and specificity, tumor markers, biological genetics.

Sfacteria, A., C. Bertani, G. Costantino, M.d. Bue, M. Paiardini, B. Cervasi, A. Piedimonte, and G.d. Vico (2003). Cyclin D1 expression in pre-cancerous and cancerous lesions of the canine mammary gland. Journal of Comparative Pathology. 128(4): 245-251. ISSN: 0021-9975.
NAL Call Number: 41.8 J82
Abstract: Overexpression of cyclin D1, the regulatory subunit of cyclin-dependent kinases (cdk4 and cdk6) involved in cell cycle control, is often found in breast cancer and other types of human cancer. Increased expression, or stability of cyclin D1 molecules may cause sufficient cdk4 activation to produce retinoblastoma protein phosphorylation independently of mitogenic signals; this results in commitment of cells to the G1 phase at mitosis. In the present study, cyclin D1 expression was investigated in pre-cancerous and cancerous lesions of the canine mammary gland by a complex experimental approach which included Western blot and immunohistochemical analysis of cyclin D1 and the related molecular system. Furthermore, to define relationships between cell growth and expression of cyclin D1, proliferative activity was studied by the AgNOR technique. The study provided the following information. Cyclin D1 overexpression was largely independent of the type of proliferative anomaly. Indeed, cyclin D1 was expressed in 60% of the pre-cancerous lesions and in 44% of cancerous lesions. Mitotic activity and cyclin D1 expression were related: mammary lesions that expressed cyclin D1 showed a high proliferative ratio, the opposite being true of cyclin D1-negative cell populations. This study may contribute to the establishment of an animal model for anti-cancer research based on cyclin D1 suppression or cdk inactivation, or both.
Descriptors: animal model, breast cancer, bitches, kinases, mammary gland diseases, mammary glands, mitosis, neoplasms, pathology, phosphorylation.

Spugnini, E.P., I. Dotsinsky, N. Mudrov, G. Cardosi, G. Citro, A. D'Avino, and A. Baldi (2007). Biphasic pulses enhance bleomycin efficacy in a spontaneous canine perianal tumors model. Journal of Experimental and Clinical Cancer Research CR 26(4): 483-7. ISSN: 0392-9078.
Abstract: Perianal tumors (adenoma and carcinoma of the hepatoid glands) are frequently reported in veterinary literature. They are locally aggressive tumors with a low tendency to metastatic spread. An hormonal ethiology has been identified for the development of perianal adenomas in male dogs, while the carcinomas are free from hormonal influence. Standard treatments include surgery, cryotherapy or, in selected cases, radiation therapy. In this article we describe the outcome of a small cohort of canine patients with perianal tumors treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy). Twelve canine patients, eight with adenoma and four with carcinoma of the perianal glands, entered the study and received two sessions of ECT under sedation. The pets had local injection ofbleomycin at the concentration of 1.5 mg/mg and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 micros each, with 1 ms interpulse intervals, were delivered by means of modified caliper and needle array electrodes or, for difficult districts, through paired needle electrode. The overall response rate was 91% with a 83% of complete response (10/12); one dog had a PR that lasted 12 months and another had progressive disease. Electrochemotherapy appears as a safe and efficacious modality for the treatment of perianal tumors and warrants further investigations.
Descriptors: anal gland neoplasms drug therapy, antibiotics, antineoplastic analysis, bleomycin analysis, dog diseases drug therapy, electrochemotherapy methods, antibiotics, antineoplastic therapeutic use, bleomycin therapeutic use, combined modality therapy, dogs, models, animal.

Suami, H., J.K. O'Neill, W.R. Pan, and G.I. Taylor (2008). Perforating lymph vessels in the canine torso: direct lymph pathway from skin to the deep lymphatics. Plastic and Reconstructive Surgery 121(1): 31-6.
Abstract: BACKGROUND: Classic anatomical lymphatic mapping in humans is represented by four territories in the torso divided by the midline and horizontal line at the L2 level. Each territory drains into the ipsilateral axillary or inguinal lymph nodes. Recently, preoperative lymphoscintigraphy for staging breast cancer and malignant melanoma has become common in the clinical arena. It reveals an undescribed direct pathway from the skin of the loin to intraabdominal lymph nodes. The authors investigated the presence of such a lymphatic route using a dog model. METHODS: The authors used seven greyhound dogs for this study. The caliber of their lymph vessels was similar to those of humans, and because of a lack of fat tissue under the integument, the vessels were identified easily. The authors applied their original radiographic technique using hydrogen peroxide and lead oxide for delineating the superficial lymphatic system. RESULTS: Lymphatic territories of the torso were classified with relation to their regional lymph nodes. The authors found perforating lymph vessels in the lumbar and gluteal regions. They originated from the skin, penetrated the abdominal wall, and then drained into paraaortic lymph nodes instead of the axillary and inguinal lymph nodes. They were always accompanied by blood vessels, especially perforating veins. CONCLUSIONS: The authors found perforating lymph vessels in a canine torso. They seem to be equivalent to the unexpected lymph pathways found in humans using lymphoscintigraphy.
Descriptors: abdomen anatomy and histology, lymphatic vessels anatomy and histology, lymphatic vessels radiography, skin anatomy and histology, cadaver, dogs, lymphography, models, animal.

Sun, H., J.M. Collins, T.J. Mangner, O. Muzik, and A.F. Shields (2003). Imaging (18f)fau (1-(2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl) uracil) in dogs. Nuclear Medicine and Biology 30(1): 25-30. ISSN: 0969-8051.
Abstract: We have studied the biodistribution of (18F)FAU ((1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)uracil), which previous work has shown is incorporated into DNA and functions as an inhibitor of DNA synthesis. It is being tested as a potential antineoplastic agent and imaging agent for PET. We have produced (18F)FAU and injected the tracer into 3 normal dogs and imaged them for up to 4 hours and removed tissues along with blood and urine samples for HPLC and activity analysis. The results showed that (18F)FAU evenly distributed to most of organs. In sharp contrast to our prior experience with thymidine and its analogs, marrow had less retention of (18F)FAU than the non-proliferating tissues.
Descriptors: radiation biology, tumor biology, cancer, neoplastic disease, diagnosis, positron emission tomography, diagnostic techniques, imaging and microscopy techniques, laboratory techniques.

Sun, S., S. Wang, N. Ge, T. Lei, Q. Lu, Z. Zhou, A. Yang, Z. Wang, and M. Sun (2007). Endoscopic ultrasound-guided interstitial chemotherapy in the pancreas: results in a canine model. Endoscopy 39(6): 530-4.
Abstract: BACKGROUND AND STUDY AIM: Interstitial chemotherapy using surgically implanted, biodegradable polymers has been reported. Our aim in this study was to investigate the feasibility and safety of endoscopic ultrasound- (EUS-) guided interstitial chemotherapy of the pancreas in a canine model. MATERIALS AND METHODS: A therapeutic 19-gauge needle with a large channel was inserted into the pancreas under EUS guidance. The polymers for sustained intratumoral release of 5-fluorouracil were implanted into the tissue by the needle. After 14 days of clinical observation, the animals were sacrificed and the tissue response to the local chemotherapy was examined. RESULTS: All the polymers were implanted successfully and no implant migration occurred. Localized tissue fibrous necrosis was achieved in the pancreas, without significant complications. The apoptotic index of the tissue within 1 cm of the focus increased. Biochemical parameters were normal in all the dogs. CONCLUSIONS: EUS-guided implantation of polymers is a safe, simple, and minimally invasive technique for interstitial chemotherapy in the pancreas.
Descriptors: antimetabolites, antineoplastic administration and dosage, endosonography, fluorouracil administration and dosage, pancreas ultrasonography, dogs, feasibility studies, injections, intralesional, models, animal, pancreas pathology, polymers administration and dosage.

Wu Jian Hui , Sun Zu Yue , Zhong En Hong , Zhu Yan , Liu Gui Ming , He Gui Lin , and Cao Lin (2003). Pathology changes of vas deferens in benign prostatic hyperplasia model of beagle dogs. Zhongguo Yaolixue Yu Dulixue Zazhi 17(3): 221-226. ISSN: 1000-3002.
Abstract: AIM: The objective of this investigation was to research the proliferation mechanism of vas deferens in benign prostatic hyperplasia. METHODS: The vas deferens, from beagle dogs which have been administered testosterone propionate(TP) to build benign prostatic hyperplasia model in vivo, was analyzed by a series of methods. Dihydrotestosterone (DHT) in vas deferens was detected by radioimmunoassay, the slices (4 mum) of vas deferens were stained with HE, and the duct area as well as the height of epithelial cell were measured with videodensitometer. The apoptosis rate was determined by flow cytometry method. The expression of prostatic specific antigen (PSA), prostatic acid phosphatase (PAP), Bcl-2 and P53 were determined by immunohistochemical methods. The nucleosomal DNA fragmentation was monitored by agarose gel electrophoresis. RESULTS: DHT level of vas deferens was increased with increasing TP doses, but there was no significant difference between groups. After being administered TP, the duct area of vas deferens was enlarged (P<0.01), and the height of epithelial cell was increased (P<0.01). The cell apoptosis rate of control was higher than that of 0.8 and 7.5 mgcntdotkg-1 TP groups(P<0.01). While there were no differences in expression of PSA, PAP and Bcl-2 between control and other groups, the expression of P53 of control was higher than that of the other groups(P<0.05). In agarose gel electrophoresis, the 200 bp base pair DNA fragments and the multiples of them were observed in control, while similar phenomenon didn't find in other groups. CONCLUSION: DHT induces vas deferens to proliferate, and the proliferation of vas deferens is related to inhibition of apoptosis.
Descriptors: endocrine system, chemical coordination and homeostasis, reproductive system, reproduction, tumor biology, benign prostatic hyperplasia, reproductive system disease, male, urologic disease, pathology changes, proliferation mechanism.
Language of Text: Chinese.

Zhang, J., X. Chen, M.S. Kent, C.O. Rodriguez, and X. Chen (2009). Establishment of a dog model for the p53 family pathway and identification of a novel isoform of p21 cyclin-dependent kinase inhibitor. Molecular Cancer Research 7(1): 67-78. ISSN: 1541-7786.
NAL Call Number: RC261.A1
Abstract: Spontaneous tumors in the dog offer a unique opportunity as models to study human cancer etiology and therapy. p53, the most commonly mutated gene in human cancers, is found to be altered in dog cancers. However, little is known about the role of p53 in dog tumorigenesis. Here, we found that on exposure to DNA damage agents or MDM2 inhibitor nutlin-3, canine p53 is accumulated and capable of inducing its target genes, MDM2 and p21. We also found that on DNA damage, canine p53 is accumulated in the nucleus, followed by MDM2 nuclear translocation and increased 53BP1 foci formation. In addition, we found that canine p63 and p73 are up-regulated by DNA damage agents. Furthermore, colony formation assay showed that canine tumor cells are sensitive to DNA damage agents and nutlin-3 in a p53-dependent manner. Surprisingly, canine p21 is expressed as two isoforms. Thus, we generated multiple canine p21 mutants and found that amino acids 129 to 142 are required, whereas amino acid 139 is one of the key determinants, for the expression of two p21 isoforms. Finally, we showed that although the full-length human p21 cDNA expresses one polypeptide, amino acid 139 seems to play a similar role as that in canine p21 for various migration patterns. Taken together, our results indicate that canine p53 family proteins have biological activities similar to human counterparts. These similarities make the dog an excellent outbred spontaneous tumor model, and the dog can serve as a translation model from benchtop to cage side and then to bedside.
Descriptors: cyclin dependent kinase inhibitor p21 genetics, tumor suppressor protein p53 physiology, amino acid sequence, antineoplastic agents pharmacology, bone neoplasms, camptothecin pharmacology, cell line, cell line, tumor, conserved sequence, cyclin dependent kinase inhibitor p21 chemistry, dna damage, dogs, doxorubicin pharmacology, kidney, melanoma, mice, models, animal, molecular sequence data, osteosarcoma, sequence alignment, sequence homology, amino acid.

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