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1.
Introduction:  Many dogs with lymphoid tumors develop resistance to chemotherapy. As a mechanism of drug resistance in canine lymphoma, ATP‐dependent drug efflux by P‐glycoprotein was reported, however, inhibition of apoptosis mediated by P53 inactivation has not been investigated. In this study, we investigated the relationship between p53 gene mutation and clinical drug resistance in canine lymphoid tumors.
Methods:  Tumor specimens were obtained from 44 dogs with lymphoid tumors. Mutations of p53 gene at exon 4–8 of these tumor tissues were examined by PCR‐SSCP (single strand conformational polymorphism) analysis, followed by nucleotide sequencing of the abnormal bands. The cases were treated with UW‐Madison protocol, and its response was evaluated by the tumor size or the number of peripheral leukemic cells.
Results:  Of the 44 dogs, 15 dogs (34%) had p53 mutation, whereas 29 dogs (66%) were devoid of p53 mutation, before or during the chemotherapeutic protocol. Rate of good response (CR and PR) to chemotherapy was significantly lower in the dogs with p53 mutation (20%) than those without p53 mutation (55%)(p = 0.022). Median overall survival duration after examination of p53 mutation was significantly shorter in dogs with p53 mutation (101days) than those without p53 mutation (223days)(p = 0.008).
Conclusions:  Lymphoid tumors with p53 mutations were shown to have worse prognosis than those without p53 mutation.  相似文献   

2.
Objective— To investigate the histologic characteristics of feline osteosarcoma (OS) and compare the histologic data with phenotypically comparable canine OS. The effects of histologic and clinical variables on survival statistics were evaluated.
Study Design— Retrospective study.
Animals— Cats (n=62) and dogs (22).
Methods— Medical records of 62 cats with OS were reviewed for clinically relevant data. Clinical outcome was obtained by telephone interview. Histologic characteristics of OS were classified using a standardized grading system. Histologic characteristics in 22 feline skeletal OS were compared with 22 canine skeletal OS of identical location and subtype. Prognostic variables for clinical outcome were determined using multivariate analysis.
Results— Feline OS was characterized by moderate to abundant cellular pleomorphism, low mitotic index, small to moderate amounts of matrix, high cellularity, and a moderate amount of necrosis. There was no significant difference between histologic variables in feline and canine OS. Histologic grade, surgery, and mitotic index significantly influenced clinical outcome as determined by multivariate analysis. Tumor invasion into vessels was not identified as a significant prognosticator.
Conclusion— Feline and canine skeletal OS have similar histologic but different prognostic characteristics.
Clinical Relevance— Prognosis for cats with OS is related to histologic grade and mitotic index of the tumor.  相似文献   

3.
In dogs, the canine transmissible venereal tumor (CTVT) is the only neoplasm which is not produced by neoplastic transformation of normal cells; the tumor is transmitted from the affected dog to healthy dogs by implantation of one or various clones of cancer cells. Thus, the CTVT of dogs analyzed in various countries reveals similar genetic characteristics and consequently CTVT is considered to have a clonal origin.The CTVTs obtained from dogs in Korea showed the T963C mutation on TP53 gene; this mutation was thought to be a molecular alteration which participates in the origin of the ancestral clone, CTVT. Nonetheless, this supposed mutation has not been identified in other studies which were carried out for the purpose of clarifying the clonal origin of CTVT. Thus we have considered it important to identify the role of the T963C mutation of the TP53 gene in the clonal origin of CTVT in dogs.Consequently the region which includes the mutation of the TP53 gene in twenty samples of CTVT obtained from various canine breeds was PCR amplified and afterwards its sequence of nucleotides was determined. We conclude that this mutation did not participate in the clonal origin of the tumor, but was acquired at a later stage.  相似文献   

4.
Introduction:  It has been reported that 40–50% of canine osteosarcoma cases have p53 mutations. The p53 tumor supressor gene plays a central role in cell cycle regulation and induction of apoptosis. We previously showed that adenoviral vector expressing canine P53 (AxCA‐cp53) inhibited growth of cultured canine osteosarcoma cell lines. Here, we evaluated anti‐tumor effect of adenovirus‐mediated p53 gene therapy on the growth of canine osteosarcomas transplanted into nude mice.
Methods:  Nine nude mice were subcutaneously injected with cells of a canine osteosarcoma cell line (POS) having p53 gene mutation. The transplanted tumors formed into nude mice were injected with AxCA‐cp53, AxCA‐LacZ (adenovirus vector expressing LacZ) or PBS (3 mice each) 7 times during 15 days. Tumor sizes were measured every 3 days for 27 days after injection with the adenovirus vectors. Expression efficiency of the adenovirus‐mediated gene transfer was examined by X‐gal staining and P53 immunostaining. Effects of the P53 expression on cell cycle control were examined by RT‐PCR for expression of p21 gene downstream of P53.
Results:  Significant differences in the tumor size was observed between the transplanted osteosarcoma tissues injected with AxCA‐cp53 and those injected with AxCA‐LacZ or PBS. Expressions of LacZ and P53 were confirmed at the injection sites of the tumors. Moreover, p21 mRNA expression was shown to be induced in the AxCA‐cp53‐injected tumors, indicating the funciton of P53 to induce cell cycle arrest.
Conclusions:  Adenoviral vector expressing canine P53 inhibited the growth of canine ostersarcoma transplanted into nude mice.  相似文献   

5.
To detect the anti-P53 antibodies of dogs with tumors, a GST-recombinant canine (rc) P53 fusion protein was expressed and purified. Immunoblot analysis was performed using this GST-rcP53 fusion protein as an antigen and serum samples from dogs suffering from tumors as primary antibodies. Out of 16 serum samples obtained from various tumor cases, four samples showed reaction with GST-rcP53. In contrast, serum from other 12 dogs with tumors, four dogs with non-neoplastic diseases and two control healthy dogs (as controls) did not show any reaction with GST-rcP53 in immunoblotting. The p53 gene mutation and the P53 protein expression were examined, using the tumor tissues to explore the relationship between the existence of the GST-rcP53 bands, gene mutations of p53 and the accumulation of P53 protein. One case, which showed a clear GST-rcP53 band, had a point mutation of the p53 cDNA and showed nuclear accumulation of P53 protein. These results suggest that the anti-P53 antibodies are also produced in tumor dogs with p53 gene mutations.  相似文献   

6.
Background: Similarities in human and canine renal cell carcinoma (RCC) epidemiology and biologic behavior suggest that molecular mechanisms of tumorigenesis may be similar in both species. Approximately 75% of RCC in people are of the clear cell subtype, up to 85% of which are associated with mutation of the von Hippel-Lindau ( VHL ) gene. The canine VHL coding deoxyribonucleic acid (DNA) shares 90% identity with the human VHL gene.
Objective: To determine whether or not RCC in dogs are associated with VHL mutations, and if so determine the prevalence, type, and location of these mutations.
Animals: Thirteen dogs with RCC, 2 dogs with primary renal sarcomas, and 10 dogs without neoplastic kidney disease.
Methods: DNA was extracted from paraffin-embedded RCC tissue; DNA extracts from paraffin-embedded and snap-frozen nonneoplastic canine kidneys and canine whole blood were used as negative controls. Polymerase chain reaction and sequencing of the 3 VHL exons was performed, and results compared with the accessioned canine sequence.
Results: All VHL exons were amplified from 9 of 13 canine RCC samples, both renal sarcomas, 8 of 10 nonneoplastic kidney samples, and canine whole blood; only exon 2 could be amplified from 2 RCC samples. Mutations were not identified in any exons. A maximal prevalence of 33.6% for VHL mutations in canine RCC was determined.
Conclusion and Clinical Importance: Although similarities between canine and human RCC merit further investigation of the dog as a model for some subtypes of renal tumors, the lower prevalence of VHL mutations suggests that oncogenesis in these 2 species differs.  相似文献   

7.
Objective— To evaluate the influence of a kidney perfusion solution on early graft function in dogs.
Study Design— Experimental, randomized study.
Animals— Intact adult male mongrel dogs (n=12).
Methods— Dogs had renal autograft transplantation without ureteroneocystotomy with contralateral nephrectomy. Kidney graft flushing with a novel organ perfusion solution was compared with flushing with saline (0.9% NaCl) solution. Serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations were measured daily posttransplant for 7 days. Ultrasound-guided renal biopsy was performed on postoperative day 1 for electron microscopic evaluation. Dogs were euthanatized on day 7.
Results— All dogs completed the study. Cr and BUN concentrations of the saline group were significantly greater than the organ perfusion solution group on each postoperative day ( P =.01 for S Cr; P =.001 for BUN). Electron micrographs of nuclei and mitochondria from convoluted proximal tubule cells indicated profound ultrastructural disruptions in the saline group and mild ultrastructural disruptions in the organ perfusion solution group.
Conclusion— Flushing solution composition can influence early graft function in live donor kidney transplantation.
Clinical Relevance— Use of a specialized flushing solution can improve early graft function in canine kidney transplantation, independent of antigen-mediated events.  相似文献   

8.
Risk factors for ventral luxation in canine total hip replacement   总被引:1,自引:1,他引:0  
Objective— To identify risk factors associated with ventral luxation (VL) of canine total hip replacement (THR), and outcome.
Study Design— Retrospective study.
Animals— Dogs (n=602) that had THR (563 cemented, 35 cementless, 4 hybrid).
Methods— Dogs (1999–2004) with VL after THR were compared with dogs with uncomplicated THR. Data included signalment, body weight, diagnosis, implant size, acetabular cup orientation, and femoral displacement ratio (FDR).
Results— VL was diagnosed in 11 (1.8%) dogs after primary THR. Including 2 other dogs that had VL after the study period, 10 (77%) of 13 dogs had VL within 7 days of surgery. Risk factors for VL included Saint Bernard-type dogs ( P =.0001), short neck extension ( P =.0005), and high angle of lateral opening in other breeds ( P =.018). There were trends toward higher risk of VL with lower FDR in Saint Bernardtypes ( P =.060), and with cementless implants ( P =.061). Twelve dogs had revision arthroplasty that was successful in all cementless and 2 cemented VL cases. Five dogs had recurrent VL and a poor outcome.
Conclusion— VL is generally an early complication of THR, with no single common risk factor identified.
Clinical Relevance— Saint Bernard types and short neck extensions are associated with increased risk of VL. Poor cup orientation is a determining factor for VL in some dogs, but a protective orientation of the acetabular cup was not found. Revision is successful in most dogs, but recurrent VL merits a guarded prognosis.  相似文献   

9.
Background: Chemotherapy for multicentric canine lymphoma has favorable results. The gastrointestinal (GI) tract is the most common extranodal site of canine lymphoma, but there have been no prospective studies to determine outcome when dogs with GI lymphoma are treated with chemotherapy.
Hypothesis: Treatment with a multiagent chemotherapy protocol is associated with a poor outcome in dogs with GI lymphoma.
Animals: Eighteen dogs with histologically confirmed GI lymphoma.
Methods: Prospective clinical trial in which dogs with GI lymphoma were treated with a 20-week combination chemotherapy protocol consisting of induction and consolidation phases.
Results: Thirteen dogs had primary GI lymphoma and 5 had multicentric lymphoma with GI involvement. The majority of the lymphomas (63%) were of T-cell origin. Overall remission rate was 56%; 9 dogs achieved a complete remission for a median of 86 days (range, 22–420 days) and 1 dog achieved a partial remission for 26 days. Overall median survival time was 77 days (range, 6–700 days). Dogs that failed to achieve a remission (10 versus 117 days; P = .002) or had diarrhea at initial presentation (70 versus 700 days; P < .001) had shorter survival times.
Conclusion and Clinical Importance: The response and survival of dogs with GI lymphoma treated with multiagent chemotherapy is poor but long-term survival is possible.  相似文献   

10.
Background: Increased cancer rates have been documented in people residing in areas around Naples characterized by illegal dumping and incineration of waste.
Hypothesis: Risk of cancer in dogs and cats is associated with waste management.
Animals: Four hundred and fifty-three dogs and cats with cancer and 1,554 cancer-free animals.
Methods: Hospital-based case-control study in Naples (low danger) and nearby cities having a history of illegal waste dumping (high danger). Odds ratio (OR) between high- and low-danger areas was calculated for all tumors and various malignancies in dogs and cats.
Results: An increased risk for cancer development was identified in dogs but not in cats residing in high-danger areas (OR: 1.55; 95% confidence interval: 1.18–2.03; P < .01). A 2.39-fold increased risk of lymphoma ( P < .01) accounted for the greater tumor frequency in dogs residing in high-danger areas. The risk of mast cell tumor and mammary cancer did not differ in dogs residing in high- or low-danger areas.
Conclusions and Clinical Importance: Waste emission from illegal dumping sites increases cancer risk in dogs residing in high-danger areas. An increased prevalence of lymphoma has been previously recognized in humans living close to illegal waste dumps. Thus, epidemiological studies of spontaneous tumors in dogs might suggest a role for environmental factors in canine and human carcinogenesis and can predict health hazards for humans.  相似文献   

11.
Tumor suppressor PTEN is mutated in canine osteosarcoma cell lines and tumors   总被引:10,自引:0,他引:10  
Canine osteosarcoma (OS) cell lines contain mutations that directly or indirectly inactivate the tumor suppressor genes p53 and retinoblastoma. Another important tumor suppressor, PTEN, is mutated in many human cancers. To determine whether inactivation of PTEN plays a role in the pathogenesis of canine OS, we studied its expression in canine OS cell lines and tumors. Four of five canine OS cell lines (CO2, C03, CO5, and CO7) constitutively express high levels of the phosphorylated form of Akt, an indirect indicator of aberrant PTEN expression. PTEN protein is essentially absent from three of these cell lines (CO2, CO5, and CO7), whereas C03 contains a potentially inactivating amino acid substitution in PTEN at codon 340. Genomic hybridization experiments indicate that CO2, CO5, and CO7 contain large deletions within the PTEN gene. Ten of 15 OS tumors exhibit variable or negative PTEN staining. Evaluation of a PTEN-negative staining tumor by Southern blotting indicates that the PTEN gene is deleted in this tumor. These results indicate that PTEN is mutated or downregulated in a high percentage of canine OS cell lines and tumors and likely plays an important role in the pathogenesis of the disease.  相似文献   

12.
Objective— To evaluate efficacy of hypotonic water as adjuvant therapy after marginal resection of canine mast cell tumors (MCT).
Study Design— Double-blinded, placebo-controlled, prospective, randomized study.
Animals— Dogs (n=30) with spontaneous, cutaneous, solitary MCT.
Methods— The wound bed of MCT, resected with margins <0.5 cm, was injected with either hypotonic or isotonic water according to a standardized protocol. Follow-up was obtained by clinical examination at 1, 2, 3, 6, and 12 months and annual telephone contact with the owner.
Results— Eighteen dogs were treated with isotonic lactated Ringer's solution and 12 dogs with hypotonic distilled water. All MCT were stage 0 tumors and most grade II. Six tumors (4 isotonic, 2 hypotonic) recurred locally, 3 of these dogs died from disease-related reasons within 4 months. The surviving 3 dogs were alive with a median survival time (ST) of 1092 days. The calculated 2-year recurrence-free rate was 92.7%; the 2-year disease-free rate 79.1%; and the 2-year survival rate 89.5%. No significant differences in local recurrence and ST were observed between treatment groups. Histologic grading was the only significant prognosticator for ST and recurrence-free periods.
Conclusion— No significant differences in local recurrence and ST were observed between adjunctive hypotonic water and placebo treatment after marginal resection of solitary MCT.
Clinical Relevance— Hypotonic water does not decrease the rate of local recurrence in dogs with solitary MCT after marginal surgical excision.  相似文献   

13.
Objectives— To investigate the histologic diagnosis and incidence of new mammary tumor growth in the remaining mammary chain tissue after regional mastectomy.
Study Design— Prospective clinical study.
Animals— Female dogs (n=99) that had excision of a single mammary tumor.
Methods— Female dogs that had regional mastectomy to remove a single tumor were followed for ≥1 year postoperatively. Data regarding tumor type, tumor recurrence, and development of metastasis were recorded.
Results— Fifty-seven (58%) dogs developed a new tumor in the ipsilateral mammary chain after the 1st surgery; 77% had repeat surgery. There was no significant correlation between the time to new tumor development and the histologic diagnosis for the 1st and 2nd tumor types. In 31 dogs, the histologic diagnosis for initial and subsequent tumors was identical and there was a significant correlation such that dogs with an initial malignant tumor are likely to develop another malignant tumor ( P =.0089). The histologic classification of the new tumor was likely to be malignant if it was located close to the side where the initial tumor had been removed ( P =.026).
Conclusions— Our results show that 58% of dogs developed a new tumor in the remaining mammary glands of the ipsilateral chain after regional mastectomy for removal of a single tumor.
Clinical Relevance— This should be taken into account when deciding on the surgical management (radical or regional mastectomy) in dogs with single mammary tumors.  相似文献   

14.
Objective— To determine the success of medical management of presumptive thoracolumbar disk herniation in dogs and the variables associated with treatment outcome.
Study Design— Retrospective case series.
Animals— Dogs (n=223) with presumptive thoracolumbar disk herniation.
Methods— Medical records from 2 clinics were used to identify affected dogs, and owners were mailed a questionnaire about success of therapy, recurrence of clinical signs, and quality of life (QOL) as interpreted by the owner. Signalment, duration and degree of neurologic dysfunction, and medication administration were determined from medical records.
Results— Eighty-three percent of dogs (185/223) were ambulatory at initial evaluation. Successful treatment was reported for 54.7% of dogs, with 30.9% having recurrence of clinical signs and 14.4% classified as therapeutic failures. From bivariable logistic regression, glucocorticoid administration was negatively associated with success ( P =.008; odds ratio [OR]=.48) and QOL scores ( P =.004; OR=.48). The duration of cage rest was not significantly associated with success or QOL. Nonambulatory dogs were more likely to have lower QOL scores ( P =.01; OR=2.34).
Conclusions— Medical management can lead to an acceptable outcome in many dogs with presumptive thoracolumbar disk herniation. Cage rest duration does not seem to affect outcome and glucocorticoids may negatively impact success and QOL. The conclusions in this report should be interpreted cautiously because of the retrospective data collection and the use of client self-administered questionnaire follow-up.
Clinical Relevance— These results provide an insight into the success of medical management for presumptive thoracolumbar disk herniation in dogs and may allow for refinement of treatment protocols.  相似文献   

15.
Few reports have investigated prognosis of canine gastrointestinal stromal tumor (GIST) cases treated by surgical resection alone. In the present study, we investigated the overall survival (OS) and prognostic factors for dogs with GIST treated by surgical complete resection alone. Fifty-three dogs were included, and the median OS was 18 months. Multivariate analysis showed that primary tumors in small intestine (P=0.04) is significantly associated with shorter OS, and median OS of the cases with cecum lesion and those with small intestine lesion was 22 and 6 months, respectively. The present study suggested primary tumor site was a novel prognostic factor for dogs with GIST treated by surgical complete resection alone.  相似文献   

16.
Objective— To (1) evaluate the analgesic effect of percutaneous cementoplasty (PC) in dogs with primary bone tumor (PBT) of the distal aspect of the radius and (2) evaluate the impact on the course of disease by adding PC to a palliative, multimodal treatment protocol in these dogs.
Study Design— Prospective pilot study.
Animals— Dogs (n=4) with PBT of the distal aspect of the radius.
Methods— Tumor lesions were filled percutaneously with polymethylmethacrylate under fluoroscopic guidance. Pamidronate was administered once in a week before PC. Radiotherapy and chemotherapy were initiated 2 and 6 weeks after PC, respectively. Force plate analysis was performed immediately before 2, and 6 weeks after PC. Survival time was defined from PC to euthanasia.
Results— Two dogs had a significant increase in peak vertical force 2 weeks after PC ( P =.043) and remained free of lameness for 18 and 20 weeks, respectively. One dog had an acute relapse after an initially lame-free period of 10 days. The remaining dog failed to improve ( P =.686). Three dogs developed at least 2 complications including transient worsening of the lameness after PC, cement leakage, wound infection and suspected thromboembolism in combination with cough and anemia. Median survival was 4.8 months (range, 1–5.7 months).
Conclusions— PC in combination with pamidronate significantly improved lameness in 2 dogs; however, PC is not risk-free. Deep wound infection, intraarticular cement leakage, and venous thrombosis were the main complications.
Clinical Relevance— PC might be a useful addition to established palliative, multimodal treatment protocols in dogs with PBT; however, because of the complications encountered PC warrants further study before routine use can be considered.  相似文献   

17.
The p53 tumor suppressor gene (TP53) is the most frequently altered gene in human cancer. Mutation of the gene has been shown to be an important mechanism of p53 pathway inactivation in a variety of human brain tumors, particularly those of astrocytic origin. Genomic DNA from a series of 37 glial and 51 nonglial canine brain tumors was sequenced to determine the frequency of TP53 gene mutations involving exons 3-9. Exonic mutations were found in 3 of 88 tumors (3.4%) and specifically in 1 of 18 astrocytic tumors (5.5%). This is markedly lower than that reported in comparable human tumors, suggesting that alternative mechanisms of p53 inactivation are likely to be present if p53 function contributes significantly to oncogenesis in canine brain tumors.  相似文献   

18.
Sixty-three cases of benign and malignant canine mammary tumors were analyzed to define the alteration of exons 5-8 for the p53 tumor suppressor gene using polymerase chain reaction direct sequence analysis with paraffin-embedded tissues. Four missense mutations were found in 38 benign mammary tumors (11%), and five missense (one tumor had two missense mutations) and one nonsense mutations were found in 25 mammary carcinomas (20%). These data suggest that the p53 gene alterations might be initiated at an early stage of canine mammary carcinogenesis and p53 mutations might be associated with malignancy. However, there was no evidence of any relationship between the p53 alterations and the histologic types of tumors or breeds of dogs.  相似文献   

19.
Objective— To investigate the efficacy of adhesive incise drapes in reducing bacterial contamination of clean canine surgical wounds.
Study Design— Randomized clinical trial.
Animals— Dogs (n=100) having elective ovariohysterectomy or stifle surgery.
Methods— Dogs were randomly assigned to 1 of 2 groups: drape or no drape. Swabs obtained from the inner edge of the surgical wound at the beginning (swab 1) and end (swab 2) of surgery were submitted for microbial culture. Number of colony forming units was counted for all positive cultures and change in bacterial counts between swabs 1 and 2 was calculated. Percentage adhesive drape adherence at the end of surgery was calculated from a digital photograph of the surgical site. Duration of surgery/anesthesia and the anesthetic induction agent used were recorded.
Results— There was a significant increase in bacterial counts between swabs 1 and 2 ( P =.001). Wound contamination was 14% (6 drape; 8 no drape; P =0.78) with Staphylococcus spp. most commonly isolated. Median percentage drape adherence at the end of surgery was 89.3% (0–100%). Duration of anesthesia was significantly related to wound contamination ( P =.013), but duration of surgery and anesthesia induction agent were not.
Conclusions— Adhesive incise drapes did not reduce wound contamination of clean canine surgical wounds.
Clinical Relevance— Use of adhesive incise drapes in clean surgical procedures is of questionable benefit in dogs.  相似文献   

20.
Objective —To evaluate lack of encephalopathy as a positive prognostic factor for complete ligation of extrahepatic congenital portosystemic shunts in dogs.
Study Design —Retrospective analysis of case records.
Animals —Dogs with extrahepatic congenital portosystemic shunts treated at the Veterinary Medical Teaching Hospital of the College of Veterinary Medicine, Cornell University, from 1985 to 1996.
Methods —The ability to completely ligate the shunting vessel in 12 nonencephalopathic dogs was compared with that in 44 encephalopathic dogs with similar shunts.
Results —Clinical signs in the 12 nonencephalopathic dogs were related to ammonium biurate urolithiasis. All 12 dogs had single extrahepatic shunting vessels. The rate of complete ligation in the nonencephalopathic dogs was 92%, whereas the rate of complete ligation in the 44 encephalopathic dogs with single extrahepatic shunts was 59%. The ability to completely ligate the shunt in nonencephalopathic dogs was significantly better ( P = .04) than in the encephalopathic dogs.
Conclusion—Lack of encephalopathy is a positive prognostic factor for complete ligation of single extrahepatic congenital portosystemic shunts.
Clinical Relevance —In most affected dogs, extrahepatic congenital portosystemic shunts in nonencephalopathic dogs can be completely ligated.  相似文献   

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