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1.
Immunohistochemical analysis of c-yes and c-erbB-2 oncogene products and p53 tumor suppressor protein in canine mammary tumors 总被引：4，自引：0，他引：4
Rungsipipat A Tateyama S Yamaguchi R Uchida K Miyoshi N Hayashi T 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》1999,61(1):27-32
In order to evaluate the involvement of c-yes and c-erbB-2 oncogene products, and p53 tumor suppressor protein in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 79 mammary tumors were analyzed immunohistochemically using antibodies against human c-yes p62 and c-erbB-2 products and p53. These 79 tumors were divided into 2 groups: 32 benign (2 adenosis, 7 simple adenomas, 14 complex adenomas, and 9 benign mixed mammary tumors) and 47 malignant tumors (26 simple adenocarcinomas, 7 complex adenocarcinomas, 5 solid carcinomas, 2 sclerosing carcinomas, 6 malignant mixed mammary tumors, and 1 malignant myoepithelioma). As a result of immunostaining, 40.6% (13/32) of the benign tumors and 21.3% (10/47) of the malignant tumors expressed the c-Yes oncogene product, ErbB-2 expression was detected in 50% (16/32) of the benign tumors and in 19.1% (9/47) of the malignant tumors. P53 expression was detected in 16% (4/25) of the benign tumors and in 30.6% (11/36) of the malignant tumors. Co-expression of c-Yes and ErbB-2, ErbB-2 and p53, and all 3 products was detected in 6, 1 and 7 tumors, respectively. 相似文献
2.
Introduction: The purpose of this study was to quantitate the risk and to describe the behavior of mast cell tumors (MCT) in Pugs.
Methods and Materials: Using the Veterinary Medicine Database, the frequency of MCT in Pugs was compared to the frequency in other dogs using a Chi‐square test. To describe the biologic behavior of MCT in pugs, cases with histologically confirmed diagnosis were identified through the University of Minnesota (UMN) Diagnostic Laboratory and Veterinary Medical Center. Histology was reviewed by a single pathologist. Survival analysis was performed to determine the impact of clinical and histologic data on survival.
Results: The frequency of MCT diagnosis in Pugs was significantly increased compared to other dogs (OR = 2.28, 95% CI = 1.81–2.86). Twenty‐five purebred Pugs with a diagnosis of MCT were identified through UMN. Multiple cutaneous tumors were documented in 14 (56%) of the dogs. Most tumors were low to intermediate grade. Only three dogs have died of their disease. Sixteen are still living (median follow‐up = 660 days). The only factors predicting survival were grade, mitotic index and tumor size.
Discussion: Our data confirms MCT predisposition in Pugs and suggests that mast cell tumors in Pugs are relatively benign, despite the presence of multiple cutaneous tumors in most cases. Multiple tumors in breeds with predisposition to MCT may indicate separate primaries rather than advanced stage disease.
This work was supported in part by NCI grants R03‐CA101030 and K08‐CA89530. 相似文献
Methods and Materials: Using the Veterinary Medicine Database, the frequency of MCT in Pugs was compared to the frequency in other dogs using a Chi‐square test. To describe the biologic behavior of MCT in pugs, cases with histologically confirmed diagnosis were identified through the University of Minnesota (UMN) Diagnostic Laboratory and Veterinary Medical Center. Histology was reviewed by a single pathologist. Survival analysis was performed to determine the impact of clinical and histologic data on survival.
Results: The frequency of MCT diagnosis in Pugs was significantly increased compared to other dogs (OR = 2.28, 95% CI = 1.81–2.86). Twenty‐five purebred Pugs with a diagnosis of MCT were identified through UMN. Multiple cutaneous tumors were documented in 14 (56%) of the dogs. Most tumors were low to intermediate grade. Only three dogs have died of their disease. Sixteen are still living (median follow‐up = 660 days). The only factors predicting survival were grade, mitotic index and tumor size.
Discussion: Our data confirms MCT predisposition in Pugs and suggests that mast cell tumors in Pugs are relatively benign, despite the presence of multiple cutaneous tumors in most cases. Multiple tumors in breeds with predisposition to MCT may indicate separate primaries rather than advanced stage disease.
This work was supported in part by NCI grants R03‐CA101030 and K08‐CA89530. 相似文献
3.
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 . 相似文献
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 . 相似文献
4.
N. Kanaya M. Yazawa M. Mochizuki R. Nishimura N. Sasaki A. Setoguchi K. Ohno H. Tsujimoto 《Veterinary and comparative oncology》2005,3(1):45-46
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
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.
C. A. Clifford E. S. Pretorius C. Weisse E. S. Siegelman K. U. Sorenmo K. Skorupski K. Drobatz K. E. Burgess R. M. Fred E. N. Glass M. Murray J. R. Solomon 《Veterinary and comparative oncology》2005,3(1):37-38
Introduction: Splenic lesions are a common finding in veterinary medicine and typically 1/2 to 2/3 of these lesions are malignant. Due to the limited accuracy of ultrasound, unnecessary exploratory surgeries/biopsies may be performed for benign lesions and treatment may be delayed for malignant ones. Splenic lesions are rare in people. MR imaging, with its inherently high soft tissue contrast, is efficacious in imaging the human spleen. We have previously demonstrated the efficacy of MRI to differentiate canine hepatic lesions. In that study 8 splenic lesions were all accurately characterized. This current study represents a further evaluation of splenic lesions.
Methods: In this prospective study, 27 dogs with splenic lesions were accrued. Histopathological/cytological confirmation of lesions occurred either before or shortly after imaging. MRI clinicians were blinded to histopathology results. MR (General Electric, 1.5 Tesla) images using a variety of sequences were obtained before and after intravenous administration of gadolinium.
Results: 32 lesions (9 malignant, 23 benign) were evaluated in 27 dogs. Lesions were confirmed via histopathology (n = 20) or cytology (n = 12). Benign lesions included, EMH (n = 7), hematoma/hemorrhage (n = 5), lymphoid hyperplasia (n = 9), and hemangioma (n = 2). Malignant lesions included anaplastic sarcoma (n = 3), malignant histiocytosis (n = 2), hemangiosarcoma (n = 2), plasma cell tumor (n = 1) and adenocarcinoma (n = 1). The overall accuracy in differentiating benign from malignant lesions was 88%(29/32 lesions). The overall sensitivity and specificity were 100%(95% CI, 66–100) and 87%(95% CI 66–97).
Conclusions: Based upon these results, MRI is both sensitive and specific in distinguishing between malignant and benign splenic lesions. 相似文献
Methods: In this prospective study, 27 dogs with splenic lesions were accrued. Histopathological/cytological confirmation of lesions occurred either before or shortly after imaging. MRI clinicians were blinded to histopathology results. MR (General Electric, 1.5 Tesla) images using a variety of sequences were obtained before and after intravenous administration of gadolinium.
Results: 32 lesions (9 malignant, 23 benign) were evaluated in 27 dogs. Lesions were confirmed via histopathology (n = 20) or cytology (n = 12). Benign lesions included, EMH (n = 7), hematoma/hemorrhage (n = 5), lymphoid hyperplasia (n = 9), and hemangioma (n = 2). Malignant lesions included anaplastic sarcoma (n = 3), malignant histiocytosis (n = 2), hemangiosarcoma (n = 2), plasma cell tumor (n = 1) and adenocarcinoma (n = 1). The overall accuracy in differentiating benign from malignant lesions was 88%(29/32 lesions). The overall sensitivity and specificity were 100%(95% CI, 66–100) and 87%(95% CI 66–97).
Conclusions: Based upon these results, MRI is both sensitive and specific in distinguishing between malignant and benign splenic lesions. 相似文献
6.
7.
M. K. Huelsmeyer A. Mitzey T. Baker M. Swaab D. H. Thamm 《Veterinary and comparative oncology》2005,3(1):57-58
Introduction: There is a wealth of information available regarding tyrosine kinase (TK) expression in human cancer, however there is minimal information regarding the expression and function of TKs in canine melanoma, and no attempt has been made to systematically define the repertoire of TKs expressed. This study employed a molecular technique called RT‐PCR display to simultaneously evaluate the expression of up to 30 different TKs in a canine melanoma cell line.
Materials and Methods: mRNA was extracted and reverse‐transcribed from the 17CM98 canine melanoma line, then subjected to PCR using degenerate primers coding for highly conserved regions which flank the kinase domains of many receptor and nonreceptor TKs. The resulting product was ligated into a plasmid vector and used to transform E. coli . Multiple colonies were isolated, and the cDNA inserts sequenced.
Results and Conclusions: Sequencing 46 clones yielded canine homologs of IGF‐1R (50%), JAK1 (17%), PDGFR‐α(11%), FGFR1 (9%), Axl (7%), c‐Abl (4%), and PTK2 (2%). Interestingly, IGF‐1R, JAK1 and Axl were detected using a similar technique in human melanoma, supporting the cross‐species validity of this assay. Given the abundance of IGF‐1R clones, we sought to determine the biologic effect of rhIGF‐1 in 17CM98 cells. IGF‐1 stimulated IGF‐1R phosphorylation, cell proliferation and VEGF production in 17CM98, and protected the cells from serum starvation‐induced apoptosis. Expression of IGF‐1R mRNA was detected in 5 of 5 additional canine melanoma cell lines evaluated, suggesting that IGF‐1R expression may be common in canine melanoma cells and providing a novel target for future therapy. 相似文献
Materials and Methods: mRNA was extracted and reverse‐transcribed from the 17CM98 canine melanoma line, then subjected to PCR using degenerate primers coding for highly conserved regions which flank the kinase domains of many receptor and nonreceptor TKs. The resulting product was ligated into a plasmid vector and used to transform E. coli . Multiple colonies were isolated, and the cDNA inserts sequenced.
Results and Conclusions: Sequencing 46 clones yielded canine homologs of IGF‐1R (50%), JAK1 (17%), PDGFR‐α(11%), FGFR1 (9%), Axl (7%), c‐Abl (4%), and PTK2 (2%). Interestingly, IGF‐1R, JAK1 and Axl were detected using a similar technique in human melanoma, supporting the cross‐species validity of this assay. Given the abundance of IGF‐1R clones, we sought to determine the biologic effect of rhIGF‐1 in 17CM98 cells. IGF‐1 stimulated IGF‐1R phosphorylation, cell proliferation and VEGF production in 17CM98, and protected the cells from serum starvation‐induced apoptosis. Expression of IGF‐1R mRNA was detected in 5 of 5 additional canine melanoma cell lines evaluated, suggesting that IGF‐1R expression may be common in canine melanoma cells and providing a novel target for future therapy. 相似文献
8.
K. N. Russell S. J. Mehler K. A. Skorupski J. L. Baez F. S. Shofer M. H. Goldschmidt 《Veterinary and comparative oncology》2005,3(1):34-34
Introduction: Gastrointestinal stromal tumors (GIST) and leiomyosarcomas (LMS) have recently been differentiated by immunohistochemical staining techniques and have been shown to have different biological behaviors in humans. Expression of the c‐kit protein, a transmembrane tyrosine kinase receptor, occurs in nearly all GISTs. The aim of this study was to differentiate canine GIST from LMS, and to compare their clinicopathological features.
Methods: Archived blocks of previously diagnosed LMS were analyzed. Immunohistochemical staining using antibodies against c‐kit, smooth muscle actin (SMA), desmin, vimentin and S100 was performed. GISTs were diagnosed based on positive c‐kit staining. LMS were diagnosed based on absence of c‐kit staining and positive SMA staining. Follow‐up information was obtained from medical records and telephone interviews with owners.
Results: Forty‐two dogs were included in the study. Mean age was 10.9 yrs (range 5–15 yrs). There were 18 females and 24 males. Twenty‐eight tumors were GISTs, 10 were LMS and 4 stained negatively for c‐kit, SMA and S100 (sarcomas). GISTs were more likely to occur in the large intestine and LMS were more common in the small intestine (p = 0.01). All were surgically excised and only two were treated with adjunctive chemotherapy. Only two GISTs and one sarcoma had metastasized at the time of surgery. Survival time in dogs discharged after surgery for GIST, LMS and sarcomas was 1123, 233 and 88 days respectively (p = 0.08).
Conclusions: Many previously diagnosed LMS should be reclassified as GIST based on the results of immunohistochemical staining. The biological behavior of these tumors appears to be different. 相似文献
Methods: Archived blocks of previously diagnosed LMS were analyzed. Immunohistochemical staining using antibodies against c‐kit, smooth muscle actin (SMA), desmin, vimentin and S100 was performed. GISTs were diagnosed based on positive c‐kit staining. LMS were diagnosed based on absence of c‐kit staining and positive SMA staining. Follow‐up information was obtained from medical records and telephone interviews with owners.
Results: Forty‐two dogs were included in the study. Mean age was 10.9 yrs (range 5–15 yrs). There were 18 females and 24 males. Twenty‐eight tumors were GISTs, 10 were LMS and 4 stained negatively for c‐kit, SMA and S100 (sarcomas). GISTs were more likely to occur in the large intestine and LMS were more common in the small intestine (p = 0.01). All were surgically excised and only two were treated with adjunctive chemotherapy. Only two GISTs and one sarcoma had metastasized at the time of surgery. Survival time in dogs discharged after surgery for GIST, LMS and sarcomas was 1123, 233 and 88 days respectively (p = 0.08).
Conclusions: Many previously diagnosed LMS should be reclassified as GIST based on the results of immunohistochemical staining. The biological behavior of these tumors appears to be different. 相似文献
9.
S. Matsuura H. Koto A. Koshino T. Okayama A. Setoguchi K. Ohno H. Tsujimoto 《Veterinary and comparative oncology》2005,3(1):50-50
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. 相似文献
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 (IC
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 IC
Conclusion: Transfection of canine mdr1 gene induced P‐gp expression and strong drug resistance in canine cell lines. 相似文献
10.
The presence of metallothioneins (MTs) were demonstrated immunohistochemically using a monoclonal antibody (E9) against a conserved epitope of I and II isoforms in canine mammary tumours. In a semiquantitative analysis MT expression in the tumour cells was observed in 54/54 cases of benign and 32/40 malignant mammary neoplasms. A statistically significant difference at the level of P<0.01 was observed for MT expression between benign and malign mammary tumours in terms of immunoreactivity score. It is concluded that immunohistochemically demonstrated MT expression is significantly associated with benign canine mammary tumours. 相似文献
11.
Murakami Y Tateyama S Rungsipipat A Uchida K Yamaguchi R 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2000,62(7):743-750
The involvement of cyclin A, cyclin D1 and p53 proteins in canine and feline tumorigenesis was analyzed immunohistochemically. In the present study, a total of 176 cases were examined, among which there were 108 canine cases (75 mammary lesions, 16 squamous cell carcinomas and 17 basal cell tumors) and 68 feline cases (43 mammary lesions, 20 squamous cell carcinomas and 5 basal cell tumors). Speckled nuclear staining for cyclin A was observed in 19/38 (50%) canine malignant mammary tumors and 18/37 (48.6%) feline mammary carcinomas, while this was not seen in benign mammary tumors of either dogs or cats. Marked intense nuclear cyclin A staining was seen in 7/16 (43.8%) canine squamous cell carcinomas and 18/20 (90.0%) feline squamous cell carcinomas. Only 3/17 (17.6%) canine basal cell tumors showed slight and scattered staining for cyclin A. Expression of cyclin D1 was very rare in both canine and feline tumors. Nuclear staining of p53 was found in 7/37 (18.9%) feline mammary carcinomas. Intense immunoreactivity for p53 was found in 6/16 (37.5%) canine squamous cell carcinomas and 8/20 (40%) feline squamous cell carcinomas. These results suggest that cyclin A may have a role in the proliferation of canine malignant mammary tumors, feline mammary carcinomas and squamous cell carcinomas of dogs and cats, and p53 may associate with the tumorigenesis of feline mammary carcinomas and squamous cell carcinomas of dogs and cats. 相似文献
12.
J. P. de Vos A. G. D. Burm B. P. Focker H. Boschloo M. Karsijns 《Veterinary and comparative oncology》2005,3(1):42-43
Introduction: Over‐expression of COX‐2 has been observed in several human and animal malignancies and is implicated in carcinogenesis through the conversion of arachidonic acid to PGE‐2. Use of platinum‐containing cytostatic agents and/or (non‐)specific COX‐2 inhibitors, has been reported as a treatment option for canine oral non‐tonsillar squamous cell carcinomas (ONT‐SCC). However, no study describes the effect of a combination of carboplatin and piroxicam on this tumor type.
Methods: 7 dogs with a T3 (WHO‐TNM) ONT‐SCC were treated with piroxicam and carboplatin. Five had bone involvement and no detectable metastasis. Two dogs without bone involvement had metastasis in the regional lymph nodes. Piroxicam was given orally 0.3 mg/kg s.i.d. Each dog was scheduled to receive between 6 and 12 carboplatin infusions (300 mg/m2 i.v.) at 3 week intervals. Ondansetron and metoclopramide were used as anti‐emetic agents. The dogs are planned to receive piroxicam on a lifelong basis.
Results: Complete response (CR) without adjuvant surgery was achieved in 4 of the 7 dogs. Two dogs needed adjuvant surgery to achieve CR. One dog had progressive disease and was euthanised 231 days after start of therapy. All the others were still alive and in CR at date of analysis. Median follow‐up was 335 days (107–689 days).
Conclusions: Our study suggests that a combination of piroxicam and carboplatin is a useful treatment option for canine ONT‐SCC. All dogs tolerated therapy well and the 57% response rate for reaching a complete and durable remission without adjuvant surgery is promising. 相似文献
Methods: 7 dogs with a T3 (WHO‐TNM) ONT‐SCC were treated with piroxicam and carboplatin. Five had bone involvement and no detectable metastasis. Two dogs without bone involvement had metastasis in the regional lymph nodes. Piroxicam was given orally 0.3 mg/kg s.i.d. Each dog was scheduled to receive between 6 and 12 carboplatin infusions (300 mg/m
Results: Complete response (CR) without adjuvant surgery was achieved in 4 of the 7 dogs. Two dogs needed adjuvant surgery to achieve CR. One dog had progressive disease and was euthanised 231 days after start of therapy. All the others were still alive and in CR at date of analysis. Median follow‐up was 335 days (107–689 days).
Conclusions: Our study suggests that a combination of piroxicam and carboplatin is a useful treatment option for canine ONT‐SCC. All dogs tolerated therapy well and the 57% response rate for reaching a complete and durable remission without adjuvant surgery is promising. 相似文献
13.
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. 相似文献
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. 相似文献
14.
Morris JS Nixon C King OJ Morgan IM Philbey AW 《Veterinary journal (London, England : 1997)》2009,179(3):422-429
TopBP1 is aberrantly expressed in human and feline mammary carcinomas, but expression of this BRCA1-related protein has not been investigated in canine mammary carcinomas. In this study, 132 canine mammary tumours (46 benign, 86 carcinomas) were examined immunohistochemically for expression of TopBP1, oestrogen receptor α (ERα), Ki67 and p53. Positive staining for TopBP1 was evident in all canine mammary lesions, although five samples had <20% positive cells. The number of samples with high levels of staining increased in different categories from benign mixed tumour to adenoma to carcinoma. Most TopBP1 staining was nuclear, but both nuclear and cytoplasmic staining were observed as the degree of malignancy increased, similar to human and feline mammary carcinomas. Benign mixed tumours, however, had more cytoplasmic staining than adenomas. Expression of p53 and the proliferation marker Ki67 increased from benign mixed tumour to adenoma to carcinoma, but the differences between benign and malignant tumours were more distinct than for TopBP1 expression. ERα expression decreased from malignant to benign tumours, although over half of the benign mixed tumours were negative. TopBP1 was expressed in canine mammary tumours at higher levels than has been reported previously for cats, although the shift in cellular localisation with malignancy was similar. 相似文献
15.
Introduction: The melanoma‐associated antigen (MAA) gp100 is a glycoprotein expressed by melanocytes and is considered to be an important target for anti‐tumour immunity in human melanoma. The aim of the current study was to characterise the canine gp100 gene with a view to its inclusion in a DNA vaccine for treatment of canine oral malignant melanoma.
Methods: RNA was extracted from eight canine oral melanomas and seven control samples (pigmented oral mucocutaneous tissue) and cDNA synthesised. PCR was performed using human gp100 primers designed to generate a 421base pair (bp) fragment. In addition to the expected pcr product, a smaller amplicon (∼260 bp) was present in all tumours and control tissues. Both PCR amplicons were cloned and sequenced. The gp100 genomic DNA sequence was identified from the dog genome resource (NCBI).
Results: The 421 bp fragment of canine gp100 shared 90.8% identity with human gp100. This partial sequence was located on dog chromosome 10 (CFA10_contig 2982). Further analysis, using the human gp100 gene as a reference, allowed the complete canine gp100 coding sequence to be identified from the dog genome. Sequence analysis of the small PCR product showed it to be a splice variant of gp100 with exon 5 deleted.
Conclusion: The canine gp100 sequence has been identified and this will allow DNA vaccine constructs containing this MAA to be developed. The splice variant of gp100 with exon 5 deleted was not tumour‐specific and was expressed in both melanomas and normal pigmented tissue. 相似文献
Methods: RNA was extracted from eight canine oral melanomas and seven control samples (pigmented oral mucocutaneous tissue) and cDNA synthesised. PCR was performed using human gp100 primers designed to generate a 421base pair (bp) fragment. In addition to the expected pcr product, a smaller amplicon (∼260 bp) was present in all tumours and control tissues. Both PCR amplicons were cloned and sequenced. The gp100 genomic DNA sequence was identified from the dog genome resource (NCBI).
Results: The 421 bp fragment of canine gp100 shared 90.8% identity with human gp100. This partial sequence was located on dog chromosome 10 (CFA10_contig 2982). Further analysis, using the human gp100 gene as a reference, allowed the complete canine gp100 coding sequence to be identified from the dog genome. Sequence analysis of the small PCR product showed it to be a splice variant of gp100 with exon 5 deleted.
Conclusion: The canine gp100 sequence has been identified and this will allow DNA vaccine constructs containing this MAA to be developed. The splice variant of gp100 with exon 5 deleted was not tumour‐specific and was expressed in both melanomas and normal pigmented tissue. 相似文献
16.
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
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
17.
Ohlerth S Dennler M Rüefli E Hauser B Poirier V Siebeck N Roos M Kaser-Hotz B 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2008,22(5):1095-1102
Background: Although B-mode ultrasound is very sensitive for the detection of splenic lesions, its specificity is low. Contrast harmonic imaging is used successfully to differentiate benign from malignant liver lesions in humans and dogs.
Hypothesis: Contrast harmonic imaging could be useful to differentiate benign and malignant splenic lesions in dogs.
Animals: Sixty dogs (clinical patients) with splenic abnormalities detected during abdominal ultrasonography.
Methods: A prospective study was performed with a Philips ATL 5000 unit for contrast pulse inversion harmonic imaging (mechanical index: 0.08, contrast medium: SonoVue). Perfusion was assessed subjectively and quantitatively.
Results: Cytology or histology identified 27 benign (hyperplasia, extramedullary hematopoiesis, hematoma) and 29 malignant (hemangiosarcoma, malignant lymphoma, malignant histiocytosis, mesenchymal tumors without classification, mast cell tumors, and others) lesions and 4 normal spleens. Except for 1 benign nodule, extensive to moderate hypoechogenicity was only seen in malignant lesions during wash-in, at peak enhancement, and during wash-out ( P = .0001, odds ratios: 37.9 [95% CI 4.5–316.5], 66.4 [95% CI 8.0–551.1], and 36.9 [95% CI 4.4–308.4]). Although all but 1 benign lesion enhanced well and were mildly hypo-, iso-, or hyperechoic in comparison with the normal spleen during all blood pool phases, marked enhancement occurred both in benign as well as in malignant splenic lesions. Quantitative perfusion values did not differ significantly between benign and malignant lesions.
Conclusions and Clinical Importance: Moderate to extensive hypoechogenicity clearly identifies canine splenic malignant lesions. In nodules with marked enhancement, contrast harmonic ultrasound is of limited value and histology is needed. 相似文献
Hypothesis: Contrast harmonic imaging could be useful to differentiate benign and malignant splenic lesions in dogs.
Animals: Sixty dogs (clinical patients) with splenic abnormalities detected during abdominal ultrasonography.
Methods: A prospective study was performed with a Philips ATL 5000 unit for contrast pulse inversion harmonic imaging (mechanical index: 0.08, contrast medium: SonoVue). Perfusion was assessed subjectively and quantitatively.
Results: Cytology or histology identified 27 benign (hyperplasia, extramedullary hematopoiesis, hematoma) and 29 malignant (hemangiosarcoma, malignant lymphoma, malignant histiocytosis, mesenchymal tumors without classification, mast cell tumors, and others) lesions and 4 normal spleens. Except for 1 benign nodule, extensive to moderate hypoechogenicity was only seen in malignant lesions during wash-in, at peak enhancement, and during wash-out ( P = .0001, odds ratios: 37.9 [95% CI 4.5–316.5], 66.4 [95% CI 8.0–551.1], and 36.9 [95% CI 4.4–308.4]). Although all but 1 benign lesion enhanced well and were mildly hypo-, iso-, or hyperechoic in comparison with the normal spleen during all blood pool phases, marked enhancement occurred both in benign as well as in malignant splenic lesions. Quantitative perfusion values did not differ significantly between benign and malignant lesions.
Conclusions and Clinical Importance: Moderate to extensive hypoechogenicity clearly identifies canine splenic malignant lesions. In nodules with marked enhancement, contrast harmonic ultrasound is of limited value and histology is needed. 相似文献
18.
Monoclonal antibodies specific for different types of intermediate filaments (cytokeratin, vimentin, desmin and neurofilaments) were used to study the histogenesis of canine mammary glands and 57 canine mammary tumors by immunocytochemistry. The intra- and interlobular duct epithelium, acinar, and intralobular myoepithelial cells stained positively for cytokeratin. Peripheral ductal and acinar cells, as well as interstitial cells, stained positively for vimentin. A similar staining pattern was seen in adenomas, complex adenomas, benign mixed tumors, ductular carcinomas, and one myoepithelioma-like tumor. Additionally, cytokeratin positive cells were scattered interstitially in one single adenoma, most complex adenomas, some benign mixed tumors, complex carcinomas, and in the malignant mixed tumors. All stromal cells stained positively for vimentin. The fibrosarcomas were positive only for vimentin, while the following expressed both desmin and cytokeratin: epithelial-like cells in one adenoma, three complex adenomas, the myoepithelioma-like tumor, the single comedo carcinoma, two complex carcinomas, the single lobular carcinoma, one malignant mixed tumor, and three osteosarcomas. Epithelial-like cells in one adenoma, six complex adenomas, two benign mixed tumors, two complex carcinomas, the lobular carcinoma, and the malignant schwannoma stained for neurofilaments. Three tumors, one adenoma, one complex adenoma, and the lobular carcinoma expressed both desmin and neurofilaments in addition to cytokeratin and vimentin. The results show the expression of different types of intermediate filaments and indicate that there might be a stem cell origin in most of the canine mammary tumors. 相似文献
19.
Objective— To evaluate the efficacy of cryosurgery for treatment of skin and subcutaneous tumors in dogs and cats.
Study Design— Prospective study.
Animals— Dogs (n=20), cats (10).
Methods— Cutaneous or subcutaneous tumors were treated by liquid nitrogen cryosurgical spray (1 cm from target tissue at 90° until a 5-mm halo of frozen tissue was achieved) for 15–60 seconds. Malignant lesions had 3 freeze–thaw cycles benign tumors, 2 cycles. The second or third freeze cycle was performed after complete thaw of the preceding freeze. Wounds healed by second intention. Follow-up was weekly for 1 month and then twice monthly until wounds healed, and final outcome was determined by telephone interview of owners.
Results— Tumor size ranged from 0.3 to 11 cm diameter with 28 (60%) being 0.3–1 cm; 8 (17%) 1.1–3 cm, and 11 (23%) >3.4 cm. Complications included edema, erythema and for extremity lesions, pain and lameness. Treated lesions (n=47) had an overall remission of 98% (mean follow-up, 345±172.02 days [range, 150–750 days]). One malignant peripheral nerve sheath tumor recurred 7 months after cryosurgical treatment.
Conclusion— Cryosurgery is an efficient method for treatment of skin and subcutaneous tumors in dogs and cats.
Clinical Relevance— Cryosurgical ablation is an effective means of treating small cutaneous or subcutaneous tumors in dogs and cats, especially in older animals where wound closure or cosmetic outcome might limit surgical excision alone. 相似文献
Study Design— Prospective study.
Animals— Dogs (n=20), cats (10).
Methods— Cutaneous or subcutaneous tumors were treated by liquid nitrogen cryosurgical spray (1 cm from target tissue at 90° until a 5-mm halo of frozen tissue was achieved) for 15–60 seconds. Malignant lesions had 3 freeze–thaw cycles benign tumors, 2 cycles. The second or third freeze cycle was performed after complete thaw of the preceding freeze. Wounds healed by second intention. Follow-up was weekly for 1 month and then twice monthly until wounds healed, and final outcome was determined by telephone interview of owners.
Results— Tumor size ranged from 0.3 to 11 cm diameter with 28 (60%) being 0.3–1 cm; 8 (17%) 1.1–3 cm, and 11 (23%) >3.4 cm. Complications included edema, erythema and for extremity lesions, pain and lameness. Treated lesions (n=47) had an overall remission of 98% (mean follow-up, 345±172.02 days [range, 150–750 days]). One malignant peripheral nerve sheath tumor recurred 7 months after cryosurgical treatment.
Conclusion— Cryosurgery is an efficient method for treatment of skin and subcutaneous tumors in dogs and cats.
Clinical Relevance— Cryosurgical ablation is an effective means of treating small cutaneous or subcutaneous tumors in dogs and cats, especially in older animals where wound closure or cosmetic outcome might limit surgical excision alone. 相似文献
20.
Annette N. Smith J. A. Vaughn M. Whatley A. Truett J. Keen 《Veterinary and comparative oncology》2005,3(1):55-55
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. 相似文献
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. 相似文献