bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antitumor Activity of Mycobacterial Cell Wall‐DNA Complex (MCC) Against Canine Urinary Bladder Transitional Cell Carcinoma Cells
Authors: Knapp D. W. , Filion B. , Filion M. C. , Phillips N. C. 
Published: September 2010

Introduction:  Mycobacterial cell wall‐DNA complex (MCC) is a bifunctional anticancer agent that induces cancer cell apoptosis and stimulates cytokine synthesis by immune cells. Intravesical MCC is currently being evaluated in humans with high‐grade urinary bladder cancer. Evaluation of MCC in dogs with transitional cell carcinoma (TCC) will allow mechanistic studies in a natural animal model of TCC, and a potentially beneficial therapy for dogs with this cancer. In this study, we have determined the anticancer activity of MCC against canine TCC cells in vitro.Methods:  Canine TCC cells (K9TCC cell line) were incubated with MCC (0.05–100 μg/ml, 0.5–72 hours). Cellular proliferation was measured by MTT reduction. Cell cycle was analyzed by flow cytometry with propidium iodide. Apoptosis was identified by flow cytometry using anti‐active‐caspase‐3/PE and anti‐cleaved‐PARP/FITC antibodies. Apoptosis‐inducing activity of 100 μg/ml MCC in combination with piroxicam (0.1–1.0 uM) was evaluated.Results:  MCC inhibited K9TCC cell proliferation in a concentration‐dependent manner (maximal activity – 45% at 100 μg/ml MCC) in association with the presence of activated caspase‐3 and cleaved PARP. Inhibition of proliferation and apoptosis‐inducing activities of MCC were independent of cell cycle phase. A thirty‐minute exposure of MCC was sufficient for optimal activity. Piroxicam (0.5 uM) enhanced apoptosis‐inducing activity of MCC.Conclusions:  MCC induces apoptosis in K9TCC cells. This activity is potentiated by piroxicam. Following positive results in vitro, in vivo studies have been initiated. One dog, treated to date, has had a minor reduction in tumor volume following the first course of treatment with no treatment‐related toxicity.
Efficacy of C/B‐OPP rescue for the treatment of relapsed canine lymphoma (1998–2004)
Authors: LeBlanc A. K. , Mauldin G. E. , Milner R. J. , Cooke K. L. , LaDue T. A. , Mauldin G. N. 
Published: September 2010

Introduction:  MOPP chemotherapy is useful for relapsed canine lymphoma. This study evaluates the efficacy of this protocol after substitution of CCNU (lomustine) or BiCNU (carmustine) for mechlorethamine (C/B‐OPP).Methods:  Patient signalment, response to chemotherapy, toxicity and survival data were abstracted from medical records of dogs from receiving C/B‐OPP between 1998 and 2004.Results:  Fifty‐eight dogs received C/B‐OPP rescue chemotherapy during the study period. The median remission duration after initial chemotherapy, consisting of CHOP‐based therapy in 91% of dogs, was 133 days (range, 10 to 932 days). Thirty‐eight of fifty‐eight dogs (66%) responded to C/B‐OPP rescue after relapse (22 CR, 16 PR), for a median of 48 days (range, 2 to 359 days). Overall, C/B‐OPP extended survival by a median of 90 days (range, 2 to 426 days). Twenty‐four dogs (41%) experienced one or more episodes of Grade II or higher gastrointestinal toxicity. Forty‐one dogs (71%) experienced one or more episodes of Grade II or higher hematologic toxicity. Twelve dogs (20%) developed regenerative anemia with diarrhea consistent with gastrointestinal hemorrhage. Treatment delays due to hematologic toxicity occurred in 37 dogs (63%). There were 16 nonfatal treatment‐related episodes of sepsis requiring hospitalization. 5 dogs died due to sepsis and/or chemotherapy‐related complications.Conclusions:  C/B‐OPP chemotherapy has activity against relapsed canine lymphoma which is similar to that of traditional MOPP rescue therapy. Moderate to severe hematologic toxicity was observed. Further work is warranted to optimize drug doses and scheduling.
Characterization, Expression and Function of c‐MET in Canine Spontaneous Cancers
Authors: Liao A. T. , McMahon M. , London C. A. 
Published: September 2010

Introduction:  Aberrant expression of the proto‐oncogene c‐Met has been noted in a variety of human cancers. In dogs, inappropriate Met expression has been identified in canine osteosarcoma (OSA) tumor samples. To better define the potential role of Met dysregulation in canine cancer, we cloned canine Met, HGF, and HGF activator and evaluated their expression patterns in a variety of canine tumor cell lines.Methods:  Canine Met, HGF, and HGF activator were cloned from normal canine liver and canine OSA cell lines using primers based on regions of homology between mouse and human sequences as well as 5′ and 3′ RACE.Results:  Inappropriate expression of Met was found in canine cell lines derived from OSAs, mast cell tumors, histiocytic sarcomas, hemangiosarcoma, and melanomas. Both HGF and HGF activator were found to be expressed in several of these tumor cell lines, providing evidence of a possible autocrine loop of Met stimulation. Incubation of canine tumor cell lines with rhHGF resulted in Met autophosphorylation and activation of the downstream signaling elements Gab1, Akt and Erk1/2. Scattering of tumor cells in response to HGF occurred under conditions of cell stress, such as serum starvation. Lastly, the Met inhibitor PHA‐665752 blocked HGF induced phosphorylation of canine Met and Gab1.Conclusions:  These studies provide evidence that similar to the case in human tumors, aberrant Met expression may play an important role in the biology of canine cancer. As such, inhibition of Met function may represent a potentially useful novel therapeutic approach.
Induction of Chemoresistance by Transfection of the Full‐Length Canine mdr1 Gene in Canine Cell Lines
Authors: Matsuura S. , Koto H. , Koshino A. , Okayama T. , Setoguchi A. , Ohno K. , Tsujimoto H. 
Published: September 2010

Introduction:  In the chemotherapy for treatment of lymphoid tumors in dogs, myelosuppression is a frequently encountered dose‐limiting factor. One possible approach to overcome myelosuppression is induction of chemoresistance in hematopoietic stem cells through expression of the mdr1 gene. A full‐length canine mdr1 cDNA clone was isolated in our laboratory. The present study was carried out to assess whether it confers multidrug resistance in canine cell lines.Materials and methods:  The full‐length canine mdr1 cDNA was inserted into an expression plasmid vector. A canine mammary tumor cell line (CIPP) and osteosarcoma cell line (OOS) were transfected with the canine mdr1 expression vector. Expression of P‐gp was examined by immunoblotting. Function of ATP‐dependent drug efflux was measured by flow cytometric analysis using Rhodamine 123. Sensitivity to chemotherapeutic drugs was shown by estimation of 50% inhibitory concentrations (IC50) of vincristine or doxorubicin.Results:  Immunoblotting of the transfected cells revealed a strong band of P‐gp detected by a monoclonal antibody directed to P‐gp. Rhodamine 123 efflux test showed an apparent drug efflux activity in the transfected cells. From the IC50 of the chemotherapeutic agents, the transfected cells showed a remarkable increase (20 to 60‐fold) in the resistance to vincristine or doxorubicin.Conclusion:  Transfection of canine mdr1 gene induced P‐gp expression and strong drug resistance in canine cell lines.
Characterization of the Biological Behavior of Appendicular Osteosarcoma in Rottweilers with a Comparison to Other Breeds
Authors: McNeill C. J. , Clifford C. A. , Shofer F. S. , Samluk M. R. , Van Winkle T. J. , Sorenmo K. U. 
Published: September 2010

Introduction:  The clinical impression of many oncologists is that Rottweilers with appendicular osteosarcoma (OSA) have an unfavorable prognosis despite standard therapy (amputation and chemotherapy). The purpose of this study was to compare clinical characteristics, biological behavior and outcome of OSA in Rottweilers to that of other breeds.Methods:  107 OSA cases were studied: 56 clinical cases (17 Rottweilers) and 54 necropsy submissions (13 Rottweilers) of OSA (3 cases overlapping). Information regarding signalment, prognostic factors, treatment and outcome was obtained from medical records and follow‐up with owners. Data were analyzed by chi‐square test, t‐test, and log rank test.Preliminary Results:  Compared to other breeds Rottweilers were more likely to have femur (23% vs. 16%) and ulna (15% vs. 3%) and less likely to have tibia (8% vs. 27%) as their primary tumor location (p = 0.04). In the necropsy group, Rottweilers had a younger age at death (6.4 vs. 10 years, p = 0.0002) and a greater body weight at diagnosis (49 vs. 37 kg, p = 0.002). No statistical differences in the age at diagnosis or survival time were noted in Rottweilers vs. other breeds. Metastasis to lymph nodes (31% vs. 10%, p = 0.08) and lungs (64% vs. 49%, p = 0.24) was more frequent in Rottweilers. There was no difference in chemotherapy drugs given; however, Rottweilers were 20 times more likely to receive NSAIDs (p = 0.0004).Conclusion:  Greater body weight with a predilection for certain tumor locations may contribute to OSA development in Rottweilers. A younger age at death may suggest a more aggressive phenotype.
Expression of E‐cadherin in Canine Anal Sac Apocrine Gland Adenocarcinoma and its Association with Survival
Authors: Polton G. A. , Adams V. , Green L. M. , Brearley M. J. , Scase T. J. 
Published: September 2010

Introduction:  Inverse associations have been shown between E‐cadherin expression and degree of differentiation in canine mammary tumours and with the acquisition of malignancy in human epithelial cancers. The purpose of this study was to examine whether there was an association between prognosis, and the distribution or intensity of immunohistochemical staining for E‐cadherin in anal sac adenocarcinoma.Methods:  Formalin‐fixed paraffin‐wax embedded canine anal sac adenocarcinoma specimens were obtained for 36 patients for whom clinical data, including survival statistics, were available. Canine mammary adenoma tissue was employed as the positive and negative controls with antibody diluent replacing the primary antibody in the latter. Samples were scored according to proportion of cells showing positive cytoplasmic membranous staining, intensity of cytoplasmic membranous staining and proportion of nuclei staining. As quality control, a sample of 10 slides was randomly selected for repeat evaluation; results exactly matched those obtained in the first assessment.Results:  All anal sac adenocarcinoma cells expressed E‐cadherin to varying degrees. There was no evidence of an association between survival time and the intensity of staining or the proportion of nuclei staining. Patients whose tumours exhibited >75% positive cytoplasmic membranous staining survived significantly longer than those exhibiting <75% staining with median survival times of 1100 and 479 days respectively (log rank test: χ2 = 3.89, 1 DF, p = 0.049).Conclusion:  Immunohistochemical evaluation of the proportion of cells in anal sac adenocarcinoma samples exhibiting positive cytoplasmic membranous staining for E‐cadherin may allow improved determination of prognoses and could aid clinical decision making.
The effect of deracoxib and piroxicam on viability of canine osteosarcoma cells in vitro
Authors: Royals S. , Farese J. , Milner R. , Lee‐Ambrose L. 
Published: September 2010

Introduction:  Cyclooxygenase‐2 (COX‐2) inhibitors are being used increasingly in cancer therapy. Although the effects of COX‐2 inhibitors have been evaluated extensively in carcinomas, less is known about their effects in sarcomas. Since the majority of dogs with appendicular osteosarcoma (OSA) are treated for pain with a non‐steroidal anti‐inflammatory drug (some COX‐2 selective) prior to definitive treatment, it is important to determine the effects that commonly used NSAIDS have on tumor cell growth.Methods:  Established canine osteosarcoma (POS, HMPOS and COS31) and canine fibroblast cell lines were maintained in culture under standard conditions. Cells were incubated with either deracoxib (1 uM to 500 uM) or piroxicam (1 uM to 1000 uM). Cell viability was assessed at 72 hours by cell counts and the MTT assay. The DNA fragmentation analysis was utilized to assess for apoptosis induction.Results:  Deracoxib concentrations ≥100 uM and piroxicam concentrations ≥500 uM significantly reduced mean cell viability of all three OSA cell lines (lowest cell viability percentages 20% and 32%, respectively). Deracoxib concentrations ≥250 uM and piroxicam concentrations ≥500 uM also reduced viability of fibroblasts; however, the cell viability percent was reduced to only 54% and 68%, respectively, of the control value. Exposure of OSA cells to cytotoxic concentrations of deracoxib and piroxicam did not result in DNA fragmentation.Conclusions:  Deracoxib and piroxicam demonstrated a cytotoxic effect on canine osteosarcoma cells. There was no evidence of apoptosis induction at the concentrations evaluated. Further investigation will need to be performed to determine whether either drug exhibits anti‐tumor effects in vivo.
Serum and Plasma Vascular Endothelial Growth Factor Levels in Various Cat Populations
Authors: Smith Annette N. , Vaughn J. A. , Whatley M. , Truett A. , Keen J. 
Published: September 2010

Introduction:  Vascular endothelial growth factor (VEGF) is one of the most important mediators of angiogenesis. Elevated levels within tumors, and in serum, plasma, and tumor effusion have been correlated with the development of metastatic disease, recurrence, and poor prognosis in many tumors in humans. Canine VEGF has been sequenced as homologous with the human form, and elevated serum and plasma VEGF have been found in dogs with hemangiosarcoma. Feline VEGF has also been sequenced, and shares homology with the human and canine forms.Materials and Methods:  Stored serum and plasma samples from normal cats, cats with various neoplasms, and cats with non‐neoplastic disease were evaluated with a commercial ELISA kit (R&D Systems, Minneapolis MN). Samples were run in duplicate, and a standard curve was performed for each plate. The data were analyzed for differences between populations, and between serum and plasma levels in the same patient to determine the optimal sample for evaluating VEGF in cats.Results:  In seven apparently healthy cats mean plasma VEGF was 95.6 pg/mL. In non‐neoplastic disease (7 cases), mean plasma VEGF was 117.3 pg/mL and mean serum VEGF level was 219.7 pg/mL. In ten tumor‐bearing patients mean plasma VEGF was 247.1 pg/mL, and mean serum VEGF was 322.3 pg/mL. Statistical analysis showed no significant difference between mean serum and plasma VEGF concentrations within each group or between groups (p > 0.05).Discussion:  Serum and plasma VEGF levels could not be used to distinguish between healthy cats and cats with neoplastic or non‐neoplastic disease.
Efficacy and Toxicity of Intracavitary Administration of Pegylated Liposomal Encapsulated Doxorubicin (DOXIL) in Dogs with Hemangiosarcoma
Authors: Sorenmo Karin , Samluk Marissa , Clifford Craig , Baez Jennifer , Overley Beth , Skorupski Katherine , Oberthaler Karen , Barrett Jeffrey , Winkle Tom Van , Seiler Gabriela , Poppenga Robert , Shofer Frances 
Published: September 2010

Introduction:  Canine hemangiosarcoma (HSA) is a fatal malignancy and most dogs die within 6–8 months of diagnosis. The spleen is a common primary site, representing 50% of all cases. These dogs typically present with clinical signs due to tumor rupture and intra‐abdominal dissemination; the abdomen is also the main site of disease progression when these patients fail. Direct delivery of chemotherapy into the abdominal cavity may therefore be a rational approach in this malignancy.Methods:  14 dogs with stage 2 or 3 splenic HSA were recruited. Doxil at a dose of 1 mg/kg was diluted in saline and administered via ultrasound‐guidance into the abdominal cavity. The dogs were scheduled to receive 4 treatments every 3 weeks. Samples of plasma and abdominal fluid were collected for pharmacokinetic analysis. All dogs were monitored for recurrence and complete necropsies were requested at death.Results:  8 dogs with stage 3 and 6 dogs with stage 2 HSA were enrolled. All 14 dogs have died, 12/14 due to tumor and 2 from other causes. There was no difference in median survival days between stages (stage 2: 244, stage 3: 125, p = .22). All 12 dogs that died due to tumor‐related causes failed with intra‐abdominal recurrence. Necropsies showed that the dogs in this study had relatively fewer extra‐abdominal metastasis compared to dogs treated with systemic chemotherapy. Pk analysis showed detectable plasma doxorubicin 1 and 2 weeks after treatment.Conclusion:  Direct abdominal administration of Doxil did not prevent intra‐abdominal recurrence; however, it appeared to provide effective systemic coverage.
Cyclooxygenase ‐2 Expression in Mammary Tumors in Dogs and its Correlation to Histologic and Biologic Behavior
Authors: De Nardi A. B. , Daleck C. R. , Souza C. H. M. , Amorin R. L. , Rodaski S. , Calderon C. , Torres R. 
Published: September 2010

Introduction:  Cyclooxygenase‐2 (Cox‐2) is the inducible form and the rate‐limiting enzyme, for conversion of arachidonic acid to prostaglandins. Cox‐2 overexpression, common in carcinomas, is associated with increased growth rate, resistance to apoptosis, angiogenesis, and overall, both local and distant aggressive behavior. Cox‐2 overexpression has been detected in human and canine mammary tumors (MTs). Histopathology of canine MT is not always predictive of biologic behavior, and anecdotally, only 50% of the malignant MTs are expected to metastasize. We hypothesize that Cox‐2 expression correlates with aggressive behavior.Methods:  This retrospective study evaluated 48 bitches, presented for excision of MT between 2000 and 2003 at FMVZ de Botucatu‐UNESP, Brasil. Follow‐up varied from 18 months to 24 months and included physical examination and thoracic radiographs. Histopathologic examination was performed in all tumors, as well as in metastatic lesions when detected in the follow‐up period. Immunohistochemistry was used to detect expression of Cox‐2 in paraffin blocks (Rabbit polyclonal anti‐PGHS‐2. Oxford Biomedical). 10 adenomas, 10 carcinomas, 10 benign mixed tumors, 10 malignant mixed tumors and 8 cases of primary carcinomas and their metastatic lesions.Results:  Expression of Cox‐2 varied among groups. Adenomas (32.1%), mixed benign tumors (38%), carcinomas (60.3%), malignant mixed tumors (65.8%), and metastatic carcinomas (81.25%) and their metastatic lesions (84.35%). Statistically significant differences (p < 0.05) were observed between the benign and malignant counterparts and between carcinomas and metastatic carcinomas.Conclusions:  Cox‐2 expression correlates with both histologic and biologic behavior in mammary carcinomas, and may serve as a predictor of metastatic potential.
An hGM‐CSF DNA‐Cationic Lipid Complexed Autologous Tumor Cell Vaccine did not Improve Remission Duration in Dogs with Lymphoma
Authors: Turek M. M. , Thamm D. H. , Mitzey A. M. , Kurzman I. D. , Huelsmeyer M. K. , Dubielzig R. R. , Vail D. M. 
Published: September 2010

Introduction:  Lymphoma is one of the most common cancers in dogs and while clinical remission can be induced using chemotherapy, very few dogs are cured. Since cytokine‐adjuvanted autologous whole‐tumor‐cell vaccines (ATCV) can induce potent antitumor immune responses against otherwise non‐immunogenic cancers we initiated a study of such an approach in dogs with lymphoma.Methods:  Following achievement of a complete remission using a 19‐week CHOP‐based chemotherapy protocol, 51 dogs with B‐cell lymphoma were randomized to receive 8 treatments (4 weekly, then 4 additional at q2wk intervals) of vaccine or lipid‐equivalent placebo. Dogs were followed monthly for assessment of remission duration and survival. Surrogate indices of immune response (delayed‐type hypersensitivity, interferon‐γ quantitative RT‐PCR, lymphocyte proliferation, and flow cytometry for lymphoma‐specific antibodies) were also investigated before and after vaccination.Results:  No significant difference in median remission duration was observed between dogs receiving vaccine (277 days) or placebo (258 days); the Kaplan‐Meier curves were virtually super‐imposable. No significant differences in surrogate indices of immune response were noted pre‐ and post‐vaccination.Conclusions:  In this context, an hGM‐CSF DNA‐cationic lipid complexed ATCV vaccine did not enhance remission duration in dogs with lymphoma, likely due to lack of vaccine‐induced tumor‐specific immunity.
Does ‘Protection for Sale’ Apply to the US Food Industries?
Authors: Lopez Rigoberto A. 
Published: September 2010

AbstractThis paper tests the Protection for Sale model in terms of the structure of protection and how realistic the estimated domestic welfare weight is relative to campaign contributions. Using data from US food manufacturing, empirical results support the key predictions for the structure of protection when either all food manufacturing industries or most of the general population is assumed to be politically organised. The domestic welfare weight is estimated as low as 0.837, the lowest econometric estimate to date, underlining that protection is for sale and that, with a qualified ‘yes’, the model fits the data for these industries.
Early Cambrian eclogites in SW Mongolia: evidence that the Palaeo‐Asian Ocean suture extends further east than expected
Authors: ŠTÍPSKÁ P. , SCHULMANN K. , LEHMANN J. , CORSINI M. , LEXA O. , TOMURHUU D. 
Published: September 2010

AbstractNewly discovered eclogites, Early Cambrian carbonates and chloritoid‐bearing metapelites form the Tsakhir Uul accretionary wedge, which was thrust during the Early Cambrian over the Mesoproterozoic Dzabkhan‐Baydrag continent. The rock association of the wedge forms a tectonic window emerging through the hangingwall Khantaishir ophiolite unit, which preserves a typical Tethyan‐type ophiolitic sequence. The eclogites correspond geochemically to T‐MORB modified by fluid circulation. They are composed of garnet, omphacite, amphibole, rutile ±muscovite ±quartz ±epidote and exhibit well‐equilibrated matrix textures. Jadeite content of the omphacite reaches up to 45 mol.%, the Si content of muscovite is between 3.40 and 3.45 p.f.u., amphibole is winchite to barroisite, but reaches tschermakitic composition at some rims, and garnet composition is grs0.24–0.36, alm0.43–0.56, py0.05–0.18, sps0.00–0.18, . The peak assemblage, together with the composition of garnet rims, omphacite, amphibole and muscovite, correspond in a pseudosection to 20−22.5 kbar and 590−610 °C. The tschermakitic rim of amphibole is interpreted as partial reequilibration on decompression below 16 kbar and ∼600−630 °C. Two muscovite separates from the eclogite yielded an Ar–Ar plateau age of 543.1 ± 3.9 Ma (1σ) and a mean age of 547.9 ± 2.6 Ma (1σ), whereas muscovite from an interbedded garnet‐chloritoid micaschist yielded an Ar–Ar plateau age of 536.9 ± 2.7 Ma (1σ); these ages are interpreted as cooling ages. The P–T data, geochemistry of eclogites and cooling ages suggest an affinity between the Tsakhir Uul wedge and the Gorny Altai and the north Mongolian blueschist belt, which are believed typical for subduction of warm oceanic lithosphere and closure of small oceanic basins. Thus, the discovery of the Tsakhir Uul eclogites represents an important finding suggesting extension of the Early Cambrian subduction system of the Central Asian Orogenic Belt far to the east in a region where it was not expected.