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1.
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
2.
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
3.
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
4.
A. B. De Nardi C. R. Daleck C. H. M. Souza R. L. Amorin S. Rodaski C. Calderon R. Torres 《Veterinary and comparative oncology》2005,3(1):56-57
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. 相似文献
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. 相似文献
5.
A. K. LeBlanc ‡§ G. E. Mauldin R. J. Milner K. L. Cooke T. A. LaDue G. N. Mauldin 《Veterinary and comparative oncology》2005,3(1):47-48
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. 相似文献
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. 相似文献
6.
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
7.
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
8.
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
9.
Karin Sorenmo Marissa Samluk Craig Clifford Jennifer Baez Beth Overley Katherine Skorupski Karen Oberthaler Jeffrey Barrett Tom Van Winkle Gabriela Seiler Robert Poppenga Frances Shofer 《Veterinary and comparative oncology》2005,3(1):55-56
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. 相似文献
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. 相似文献
10.
J. Turrel B. Burke S. Ullman M. McEntee R. Page 《Veterinary and comparative oncology》2005,3(1):52-53
Introduction: Greater than 50% of dogs with thyroid tumors present with surgically unresectable disease for which external beam radiotherapy has been reported to prolong survival. The success of 131 I for control of thyroid tumors in cats and in humans suggests such therapy may also play a role in the management of canine thyroid cancer.
Methods: Thirty‐nine dogs with WHO stage II/III (invasive or ectopic; n = 32) or IV (metastatic; n = 7) thyroid tumors were treated with131 I alone. Changes in thyroid function, 99M Tc‐pertechnetate (99M Tc) scintigraphic changes, and tumor response were recorded. Dogs with ventral cervical tumors were evaluated for feasibility of surgical resection following 131 I.
Results: Median overall survival was 839 days and 366 days for dogs with stage II/III and stage IV tumors, respectively. Thyroid hormone status, site and surgical resection were not associated with outcome in dogs with stage II/III tumors. Three dogs developed severe bone marrow suppression.
Conclusions: These findings suggest131 I should be investigated more thoroughly in dogs with thyroid tumors not considered surgical candidates to more clearly characterize the indications for therapy and followup recommendations. 131 I dosimetry in dogs with thyroid tumors remains problematic. Administration of 131 I is currently based on empiric recommendations and, in general, the treatment is well tolerated although additional studies are indicated to optimize response and minimize toxicity. 相似文献
Methods: Thirty‐nine dogs with WHO stage II/III (invasive or ectopic; n = 32) or IV (metastatic; n = 7) thyroid tumors were treated with
Results: Median overall survival was 839 days and 366 days for dogs with stage II/III and stage IV tumors, respectively. Thyroid hormone status, site and surgical resection were not associated with outcome in dogs with stage II/III tumors. Three dogs developed severe bone marrow suppression.
Conclusions: These findings suggest
11.
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
12.
C. J. Henry A. W. Hahn J. W. Tyler H. S. Steinberg C. W. Caldwell 《Veterinary and comparative oncology》2005,3(1):33-33
Introduction: Surveillance, Epidemiology & End Results (SEER) data indicate that non‐Hodgkin's lymphoma (NHL) is approximately 50% more common among men than women. A similar male predisposition is reported for canine lymphoma, yet the underlying role of gender in lymphoma etiology remains elusive. Because similarities exist between canine lymphoma and NHL, databases including the Veterinary Medical Database (VMDB) and Veterinary Cancer Registry (VCR) may prove useful in understanding lymphoma epidemiology. This study sought to determine the relationship between gender and development of canine lymphoma.
Materials: Data from 1980 to 2000 were retrieved from the VMDB and sorted by gender and reproductive status. Spayed or neutered dogs diagnosed with lymphoma were compared to intact dogs seen each year in each gender category using a two‐tailed Student's t‐test. The VCR was searched for all canine lymphoma cases. The number of cases in each gender group was compared to the number of cancer diagnoses per group using a Chi‐square test (3 degrees of freedom). Differences were deemed significant when P < 0.050.
Results: The VMDB included 15,091 lymphoma cases in a population of 1.34 million dogs. In the VCR database, 394 lymphoma cases were identified amongst 6,070 canine cancer diagnoses. In both analyses, intact females were significantly less likely to develop lymphoma than were other gender groups.
Conclusions: In dogs, as in people, female gender and intact reproductive status appears to be protective against the development of lymphoma. This data suggests that further examination of the role of estrogen in lymphoma prevention is warranted. 相似文献
Materials: Data from 1980 to 2000 were retrieved from the VMDB and sorted by gender and reproductive status. Spayed or neutered dogs diagnosed with lymphoma were compared to intact dogs seen each year in each gender category using a two‐tailed Student's t‐test. The VCR was searched for all canine lymphoma cases. The number of cases in each gender group was compared to the number of cancer diagnoses per group using a Chi‐square test (3 degrees of freedom). Differences were deemed significant when P < 0.050.
Results: The VMDB included 15,091 lymphoma cases in a population of 1.34 million dogs. In the VCR database, 394 lymphoma cases were identified amongst 6,070 canine cancer diagnoses. In both analyses, intact females were significantly less likely to develop lymphoma than were other gender groups.
Conclusions: In dogs, as in people, female gender and intact reproductive status appears to be protective against the development of lymphoma. This data suggests that further examination of the role of estrogen in lymphoma prevention is warranted. 相似文献
13.
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
14.
C. J. McNeill C. A. Clifford F. S. Shofer M. R. Samluk T. J. Van Winkle K. U. Sorenmo 《Veterinary and comparative oncology》2005,3(1):51-52
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. 相似文献
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. 相似文献
15.
Objective— To investigate mutations of the TP53 gene in canine osteosarcoma (OS).
Study Design— Clinical historic cohort study.
Animals— Client-owned dogs.
Methods— OS (n=59) were screened for mutations of the complete TP53 gene using polymerase chain reaction and the mutation was analyzed by single-strand conformational polymorphism. Clinical outcome of dogs with TP53-mutated OS were compared with dogs with OS without a mutation after complete surgical excision of the primary tumor.
Results— TP53 gene mutations were observed in 24 of 59 (40.7%) OS; 3 mutated OS had 2 mutations. The alterations consisted mainly of point mutations (74%). Dogs with mutated OS had a significantly shorter survival time (ST) after surgery than dogs with normal tumor TP53 gene expression ( P =.03). Other significant prognosticators for ST and disease-free interval included elevated serum alkaline phosphatase ( P <.01) and tumor grade ( P =.01).
Conclusion— TP53 genetic mutations are common in canine OS and may have a prognostic value.
Clinical Relevance— Mutations of the TP53 gene may influence survival and should be considered when evaluating canine OS. 相似文献
Study Design— Clinical historic cohort study.
Animals— Client-owned dogs.
Methods— OS (n=59) were screened for mutations of the complete TP53 gene using polymerase chain reaction and the mutation was analyzed by single-strand conformational polymorphism. Clinical outcome of dogs with TP53-mutated OS were compared with dogs with OS without a mutation after complete surgical excision of the primary tumor.
Results— TP53 gene mutations were observed in 24 of 59 (40.7%) OS; 3 mutated OS had 2 mutations. The alterations consisted mainly of point mutations (74%). Dogs with mutated OS had a significantly shorter survival time (ST) after surgery than dogs with normal tumor TP53 gene expression ( P =.03). Other significant prognosticators for ST and disease-free interval included elevated serum alkaline phosphatase ( P <.01) and tumor grade ( P =.01).
Conclusion— TP53 genetic mutations are common in canine OS and may have a prognostic value.
Clinical Relevance— Mutations of the TP53 gene may influence survival and should be considered when evaluating canine OS. 相似文献
16.
J. Liao † P. Gregor F. Orlandi D. M. Craft C. Leung A. N. Houghton J. D. Wolchok P. J. Bergman 《Veterinary and comparative oncology》2005,3(1):48-48
Introduction: Xenogeneic melanosomal differentiation antigens, delivered in the form of a plasmid DNA vaccine, can overcome host immune ignorance/tolerance in preclinical animals to melanoma by: 1) generating humoral and cytotoxic T cell responses and 2) inducing protection from tumor challenge. Initial trials of human tyrosinase (huTyr) DNA vaccination of dogs with advanced malignant melanoma (Bergman et al , 2003) demonstrated safety and prolongation of survival with this therapeutic modality. We investigated antigen‐specific immunity in dogs receiving huTyr DNA vaccination.
Methods: Three cohorts of three dogs each with advanced (WHO stage II‐IV) canine malignant melanoma (CMM) received four biweekly IM injections (dose levels 100, 500, or 1,500 ug, respectively/vaccination) of huTyr plasmid DNA via the Biojector2000 jet delivery device. Sera samples were taken before and after vaccination to detect specific antibody formation to huTyr by Enzyme‐Linked ImmunoSorbent Assays (ELISAs) and flow‐cytometry.
Results: Three dogs have measurable, 2 to 4 fold huTyr‐specific antibody titers. Preliminary studies by flow‐cytometry have confirmed antibody response to huTyr by positive binding to endogenous human tyrosinase in SK‐Mel188 cells using post‐vaccinate serum.
Conclusions: Xenogeneic (huTyr) DNA vaccination generates antigen‐specific humoral responses, which may partially explain the previously reported clinical efficacy and anti‐tumor responses. Ongoing studies include: 1) a comprehensive analysis by flow‐cytometry to detect huTyr‐specific antibodies and 2) a quantitative measure of potential cytotoxic T‐cell responses in these dogs by the DNA vaccination. 相似文献
Methods: Three cohorts of three dogs each with advanced (WHO stage II‐IV) canine malignant melanoma (CMM) received four biweekly IM injections (dose levels 100, 500, or 1,500 ug, respectively/vaccination) of huTyr plasmid DNA via the Biojector2000 jet delivery device. Sera samples were taken before and after vaccination to detect specific antibody formation to huTyr by Enzyme‐Linked ImmunoSorbent Assays (ELISAs) and flow‐cytometry.
Results: Three dogs have measurable, 2 to 4 fold huTyr‐specific antibody titers. Preliminary studies by flow‐cytometry have confirmed antibody response to huTyr by positive binding to endogenous human tyrosinase in SK‐Mel188 cells using post‐vaccinate serum.
Conclusions: Xenogeneic (huTyr) DNA vaccination generates antigen‐specific humoral responses, which may partially explain the previously reported clinical efficacy and anti‐tumor responses. Ongoing studies include: 1) a comprehensive analysis by flow‐cytometry to detect huTyr‐specific antibodies and 2) a quantitative measure of potential cytotoxic T‐cell responses in these dogs by the DNA vaccination. 相似文献
17.
G. A. Polton V. Adams L. M. Green M. J. Brearley T. J. Scase 《Veterinary and comparative oncology》2005,3(1):53-54
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. 相似文献
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: χ
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. 相似文献
18.
A. Borgatti&#;Jeffreys S. B. Hooser M. A. Miller R. M. Thomas A. deGortari M. D. Lucroy 《Veterinary and comparative oncology》2005,3(1):49-50
Introduction: Photodynamic therapy (PDT) involves the light activation of a drug within a tumor causing selective tumor cell death. Unfortunately, some photosensitizing drugs have been associated with adverse reactions in veterinary patients. Zinc phthalocyanine tetrasulfonate (ZnPcS4) is a promising second‐generation photosensitizer for use in veterinary medicine, however, it cannot be applied clinically until safety and efficacy data are available.
Methods: Increasing intraperitoneal doses of ZnPcS4 were given to Swiss Webster mice to assess acute toxicity. Based on mouse toxicity data, a phase I clinical trial of ZnPcS4‐based PDT in tumor‐bearing dogs was designed, using an accelerated titration scheme starting at 0.5% of the minimum toxic dose in mice. 24‐hours after ZnPcS4 administration tumors were irradiated with 675 nm light and dogs were evaluated by routine hematology and serum biochemistry at regular intervals after PDT.
Results: Doses >125 mg/kg were associated with acute toxicity and mortality in Swiss Webster mice, suggesting the minimum toxic dose is 120–125 mg/kg. One dog, a Golden retriever with a massive malignant fibrous histiocytoma, has been entered into the phase I clinical trial. No deleterious effects were noted after ZnPcS4 administration. Within 48 hours of PDT, the tumor was dark and necrotic, with no grossly visible changes to the surrounding normal tissues. Histological examination of the PDT‐treated tumor confirmed widespread necrosis and thrombosis consistent with PDT‐mediated damage. The owner reported no adverse effects after treatment.
Conclusions: Although preliminary data are encouraging, additional evaluation of ZnPcS4‐based PDT is required to determine its role in veterinary medicine. 相似文献
Methods: Increasing intraperitoneal doses of ZnPcS4 were given to Swiss Webster mice to assess acute toxicity. Based on mouse toxicity data, a phase I clinical trial of ZnPcS4‐based PDT in tumor‐bearing dogs was designed, using an accelerated titration scheme starting at 0.5% of the minimum toxic dose in mice. 24‐hours after ZnPcS4 administration tumors were irradiated with 675 nm light and dogs were evaluated by routine hematology and serum biochemistry at regular intervals after PDT.
Results: Doses >125 mg/kg were associated with acute toxicity and mortality in Swiss Webster mice, suggesting the minimum toxic dose is 120–125 mg/kg. One dog, a Golden retriever with a massive malignant fibrous histiocytoma, has been entered into the phase I clinical trial. No deleterious effects were noted after ZnPcS4 administration. Within 48 hours of PDT, the tumor was dark and necrotic, with no grossly visible changes to the surrounding normal tissues. Histological examination of the PDT‐treated tumor confirmed widespread necrosis and thrombosis consistent with PDT‐mediated damage. The owner reported no adverse effects after treatment.
Conclusions: Although preliminary data are encouraging, additional evaluation of ZnPcS4‐based PDT is required to determine its role in veterinary medicine. 相似文献
19.
D. W. Knapp B. Filion M. C. Filion N. C. Phillips 《Veterinary and comparative oncology》2005,3(1):46-47
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. 相似文献
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. 相似文献
20.
B. M. Pressler L. E. Williams J. A. Ramos-Vara K. I. Anderson 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(3):592-597
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
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