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1.
A. K. LeBlanc G. E. Mauldin R. J. Milner T. A. LaDue G. N. Mauldin J. W. Bartges 《Veterinary and comparative oncology》2006,4(1):21-32
Mechlorethamine (Mustargen®, Oncovin® (vincristine), procarbazine and prednisone (MOPP) chemotherapy is useful for relapsed canine lymphoma. This study evaluates the efficacy of MOPP after substitution of CCNU (lomustine, LOPP protocol) or BCNU (carmustine, BOPP protocol) for mechlorethamine in 60 dogs with relapsed lymphoma. Seven of 14 (50%) dogs treated with BOPP responded, for a median of 129.5 days for complete responders (range 9–354 days) and a median of 140 days for partial responders (range 4–276 days). Twenty‐three of 44 (52%) dogs treated with LOPP responded for a median of 112 days for complete responders (range 48–250 days) and a median of 84.5 days for partial responders (range 69–290 days). Two dogs receiving a combination of LOPP and BOPP partially responded for 28 and 163 days, respectively. With BOPP chemotherapy, nine dogs (20.5%) and seven dogs (50%) had one or more episodes of Grade II or higher neutropenia and thrombocytopenia, respectively. Seven dogs (50%) had one or more episodes of Grade II or higher gastrointestinal toxicity. While receiving LOPP chemotherapy, 28 dogs (63.6%) and 17 dogs (38.6%) had one or more episodes of Grade II or higher neutropenia and thrombocytopenia, respectively. Seventeen dogs (38.6%) had one or more episodes of Grade II or higher gastrointestinal toxicity. Overall, there were 17 non‐fatal treatment‐related episodes of sepsis requiring hospitalization. Eight dogs (13%) died or were euthanized because of treatment‐related sepsis and/or chemotherapy‐related complications. Severe haematologic toxicity, coupled with the improved response duration observed in dogs receiving reduced doses during B/L‐OPP rescue, underscores the need for protocol optimization. 相似文献
2.
M. M. Turek D. H. Thamm A. M. Mitzey I. D. Kurzman M. K. Huelsmeyer R. R. Dubielzig D. M. Vail 《Veterinary and comparative oncology》2005,3(1):59-59
Introduction: Lymphoma is one of the most common cancers in dogs and while clinical remission can be induced using chemotherapy, very few dogs are cured. Since cytokine‐adjuvanted autologous whole‐tumor‐cell vaccines (ATCV) can induce potent antitumor immune responses against otherwise non‐immunogenic cancers we initiated a study of such an approach in dogs with lymphoma.
Methods: Following achievement of a complete remission using a 19‐week CHOP‐based chemotherapy protocol, 51 dogs with B‐cell lymphoma were randomized to receive 8 treatments (4 weekly, then 4 additional at q2wk intervals) of vaccine or lipid‐equivalent placebo. Dogs were followed monthly for assessment of remission duration and survival. Surrogate indices of immune response (delayed‐type hypersensitivity, interferon‐γ quantitative RT‐PCR, lymphocyte proliferation, and flow cytometry for lymphoma‐specific antibodies) were also investigated before and after vaccination.
Results: No significant difference in median remission duration was observed between dogs receiving vaccine (277 days) or placebo (258 days); the Kaplan‐Meier curves were virtually super‐imposable. No significant differences in surrogate indices of immune response were noted pre‐ and post‐vaccination.
Conclusions: In this context, an hGM‐CSF DNA‐cationic lipid complexed ATCV vaccine did not enhance remission duration in dogs with lymphoma, likely due to lack of vaccine‐induced tumor‐specific immunity. 相似文献
Methods: Following achievement of a complete remission using a 19‐week CHOP‐based chemotherapy protocol, 51 dogs with B‐cell lymphoma were randomized to receive 8 treatments (4 weekly, then 4 additional at q2wk intervals) of vaccine or lipid‐equivalent placebo. Dogs were followed monthly for assessment of remission duration and survival. Surrogate indices of immune response (delayed‐type hypersensitivity, interferon‐γ quantitative RT‐PCR, lymphocyte proliferation, and flow cytometry for lymphoma‐specific antibodies) were also investigated before and after vaccination.
Results: No significant difference in median remission duration was observed between dogs receiving vaccine (277 days) or placebo (258 days); the Kaplan‐Meier curves were virtually super‐imposable. No significant differences in surrogate indices of immune response were noted pre‐ and post‐vaccination.
Conclusions: In this context, an hGM‐CSF DNA‐cationic lipid complexed ATCV vaccine did not enhance remission duration in dogs with lymphoma, likely due to lack of vaccine‐induced tumor‐specific immunity. 相似文献
3.
Rassnick KM Mauldin GE Al-Sarraf R Mauldin GN Moore AS Mooney SC 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2002,16(5):576-580
The purpose of this retrospective study was to evaluate the efficacy and toxicity of the MOPP chemotherapy protocol (mechlorethamine, vincristine, procarbazine, and prednisone) as a rescue regimen in dogs with lymphoma. One hundred seventeen dogs that had resistance to previously administered chemotherapy were evaluated. Before treatment with MOPP, all dogs received a median of 6 chemotherapy drugs for a median duration of 213 days. Thirty-one percent (36 of 117) had a complete response (CR) to MOPP for a median of 63 days, and 34% (40 of 117) had a partial response (PR) for a median of 47 days. Sixteen percent (19 of 117) had stable disease (SD) for a median of 33 days. Predictors for response to MOPP were not identified. Gastrointestinal (GI) toxicity occurred in 28% (33 of 117) of the dogs, and 13% (15 dogs) required hospitalization. Five dogs developed septicemia, and 2 died as a result. MOPP was an effective treatment for dogs with resistant lymphoma and was well tolerated by the majority of affected dogs. 相似文献
4.
P. J. Bergman † M. A. Camps&#;Palau J. A. McKnight N. F. Leibman C. A. Novosad S. Brenn S. N. Ettinger M. M. Endicott K. Finora D. Craft C. Leung J. Liao I. Riviere A. E. Hohenhaus A. Houghton M. Perales J. D. Wolchok 《Veterinary and comparative oncology》2005,3(1):35-36
Introduction: Canine malignant melanoma (CMM) is an aggressive neoplasm treated with surgery and/or fractionated RT; however, metastatic disease is common and chemoresistant. Preclinical and clinical studies by our laboratory and others have shown that xenogeneic DNA vaccination with tyrosinase family members can produce immune responses resulting in tumor rejection or protection and prolongation of survival. The potency of DNA vaccines can be further enhanced by adding DNA encoding cytokine genes. We have shown in preclinical mouse models that GM‐CSF DNA enhances immune responses and tumor protection. These studies provided the impetus for murine tyrosinase (muTyr) ± human GM‐CSF (huGM‐CSF) DNA vaccination in CMM.
Materials & Methods: Two groups of five dogs each with advanced (WHO stage II‐IV) CMM received four biweekly IM injections (100 ug or 500 ug, respectively/vaccination) of plasmid DNA encoding muTyr via the Biojector2000 jet delivery device. Subsequently, three groups of nine dogs each with advanced CMM received four biweekly IM injections of plasmid DNA encoding muTyr (50 ug), huGM‐CSF (3 dogs each at 100/400/800 ug) or both.
Results: Minimal to mild pain was noted on vaccination and no toxicity or induction of autoimmunity was seen. The KM median survival time was 224 days (100/500 ug muTyr), 278 days (50 ug muTyr), 140 days (huGM‐CSF) and >265 days (muTyr & huGM‐CSF; 6 dogs still alive).
Conclusions: The results of these trials demonstrate that xenogeneic DNA vaccination continues to be a safe and potentially therapeutic modality for CMM. These results also warrant further evaluation of this novel therapeutic in a Phase II setting. 相似文献
Materials & Methods: Two groups of five dogs each with advanced (WHO stage II‐IV) CMM received four biweekly IM injections (100 ug or 500 ug, respectively/vaccination) of plasmid DNA encoding muTyr via the Biojector2000 jet delivery device. Subsequently, three groups of nine dogs each with advanced CMM received four biweekly IM injections of plasmid DNA encoding muTyr (50 ug), huGM‐CSF (3 dogs each at 100/400/800 ug) or both.
Results: Minimal to mild pain was noted on vaccination and no toxicity or induction of autoimmunity was seen. The KM median survival time was 224 days (100/500 ug muTyr), 278 days (50 ug muTyr), 140 days (huGM‐CSF) and >265 days (muTyr & huGM‐CSF; 6 dogs still alive).
Conclusions: The results of these trials demonstrate that xenogeneic DNA vaccination continues to be a safe and potentially therapeutic modality for CMM. These results also warrant further evaluation of this novel therapeutic in a Phase II setting. 相似文献
5.
E.M. Brodsky G.N. Maudlin J.L. Lachowicz G.S. Post 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(3):578-584
Background: Dogs with multicentric lymphoma are treated with various cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy protocols with variable success.
Objectives: To describe the progression-free survival (PFS) time and overall survival time (OST) of dogs with T-cell lymphoma or hypercalcemic lymphoma treated with l -asparaginase and mechlorethamine, vincristine, prednisone, procarbazine (MOPP).
Animals: Fifty dogs with T-cell lymphoma, hypercalcemic lymphoma, or both treated at 3 referral veterinary hospitals.
Methods: Retrospective study. Case were selected based on histologic or cytologic diagnosis of lymphoma; presence of the T-cell phenotype, presence of hypercalcemia or both; and absence of previous chemotherapy. The T-cell phenotype was determined by flow cytometry, immunocytochemistry, immunohistochemistry, or polymerase chain reaction of antigen receptor rearrangement.
Results: The overall response rate was 98% (78% complete response, 20% partial response). The median PFS for the entire study population was 189 days with 25% PFS at 939 days. The median OST for the entire study population was 270 days with 25% surviving 939 days. Twenty percent of the dogs required hospitalization for treatment related complications.
Conclusions and clinical importance: l -Asp/MOPP chemotherapy might result in longer PFS and OST for dogs with multicentric T-cell lymphoma, dogs with hypercalcemic lymphoma or both, than achieved with CHOP. 相似文献
Objectives: To describe the progression-free survival (PFS) time and overall survival time (OST) of dogs with T-cell lymphoma or hypercalcemic lymphoma treated with l -asparaginase and mechlorethamine, vincristine, prednisone, procarbazine (MOPP).
Animals: Fifty dogs with T-cell lymphoma, hypercalcemic lymphoma, or both treated at 3 referral veterinary hospitals.
Methods: Retrospective study. Case were selected based on histologic or cytologic diagnosis of lymphoma; presence of the T-cell phenotype, presence of hypercalcemia or both; and absence of previous chemotherapy. The T-cell phenotype was determined by flow cytometry, immunocytochemistry, immunohistochemistry, or polymerase chain reaction of antigen receptor rearrangement.
Results: The overall response rate was 98% (78% complete response, 20% partial response). The median PFS for the entire study population was 189 days with 25% PFS at 939 days. The median OST for the entire study population was 270 days with 25% surviving 939 days. Twenty percent of the dogs required hospitalization for treatment related complications.
Conclusions and clinical importance: l -Asp/MOPP chemotherapy might result in longer PFS and OST for dogs with multicentric T-cell lymphoma, dogs with hypercalcemic lymphoma or both, than achieved with CHOP. 相似文献
6.
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
7.
S. Boston N. Ehrhart W. Dernell M. Lafferty S. Withrow 《Veterinary and comparative oncology》2005,3(1):36-37
Introduction: Stage III osteosarcoma generally carries a grave prognosis. Despite this, some owners elect to treat using palliative or curative intent protocols. The purpose of this study was to determine the survival times for dogs with stage III osteosarcoma that undergo treatment and to evaluate the variables that affect survival time.
Methods: Retrospective study using the CSU Animal Cancer Center osteosarcoma data base. Search criteria included dogs diagnosed with osteosarcoma 1985–2004 with metastasis at the time of presentation. Dogs were excluded if they were euthanized at the time of diagnosis (13 dogs) or lost to follow‐up (10 dogs). There were 90 cases for analysis. The survival times were compared based on the primary tumor site, site of metastasis, treatment given, age, sex and breed.
Results: Survival times in days ranged from 0 to 1583 days. The overall median survival time was 76 days. The one‐year, two‐year and three‐year percent survival were 7%, 4.7% and 3.5%, respectively. Treatment included various combinations of chemotherapy, surgery, radiation therapy, bisphosphonates and NSAIDs. Findings included an increased survival time with surgery and adjuvant therapy compared with surgery alone and a decreased survival time with metastasis to the lung or lymph node.
Conclusions: Treatment of dogs with stage III osteosarcoma can result in variable survival times. Multimodality therapy appears to result in longer survival times. Metastasis to the lung or lymph node correlated with a decreased survival time. 相似文献
Methods: Retrospective study using the CSU Animal Cancer Center osteosarcoma data base. Search criteria included dogs diagnosed with osteosarcoma 1985–2004 with metastasis at the time of presentation. Dogs were excluded if they were euthanized at the time of diagnosis (13 dogs) or lost to follow‐up (10 dogs). There were 90 cases for analysis. The survival times were compared based on the primary tumor site, site of metastasis, treatment given, age, sex and breed.
Results: Survival times in days ranged from 0 to 1583 days. The overall median survival time was 76 days. The one‐year, two‐year and three‐year percent survival were 7%, 4.7% and 3.5%, respectively. Treatment included various combinations of chemotherapy, surgery, radiation therapy, bisphosphonates and NSAIDs. Findings included an increased survival time with surgery and adjuvant therapy compared with surgery alone and a decreased survival time with metastasis to the lung or lymph node.
Conclusions: Treatment of dogs with stage III osteosarcoma can result in variable survival times. Multimodality therapy appears to result in longer survival times. Metastasis to the lung or lymph node correlated with a decreased survival time. 相似文献
8.
N. C. Northrup T. L. Gieger C. E. Kosarek C. F. Saba B. E. LeRoy T. M. Wall K. R. Hume M. O. Childress D. A. Keys 《Veterinary and comparative oncology》2009,7(1):38-45
Forty-one dogs with resistant lymphoma were treated with a modified MOPP (mechlorethamine, vincristine, procarbazine and prednisone) protocol (MPP [mechlorethamine, procarbazine and prednisone] administered on a 21-day cycle, shortened from the 28-day MOPP cycle). The overall response rate to MPP was 34% for a median of 56 days (95% confidence interval 30–238). Seventeen percent of dogs had a complete response for a median duration of 238 days, 17% had a partial response for a median of 56 days and 32% had stable disease for a median of 24 days. Histological grade or cell morphology on cytology was associated with response. Minimal toxicity was observed with the MPP protocol, suggesting that further dose intensification or addition of another chemotherapeutic agent would be possible. 相似文献
9.
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
10.
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
11.
Kelley Zimmerman Koranda A. Walsh Jonathan T. Ferrari Nicholas S. Keuler Matthew J. Atherton Jennifer A. Lenz 《Veterinary and comparative oncology》2023,21(3):503-508
Multi-agent chemotherapy successfully induces remission in most naïve, high-grade canine lymphoma patients; however, disease recurrence is common. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) is an effective rescue protocol used to re-induce remission, but is associated with gastrointestinal toxicity and can be a less desirable option for patients that previously failed vincristine-containing protocols. Therefore, alternative members of the vinca alkaloid family, such as vinblastine, could be potentially advantageous as substitutes for vincristine to reduce gastrointestinal toxicity and chemoresistance. The objective of this study was to report the clinical outcomes and toxicity of 36 dogs with relapsed or refractory multicentric lymphoma treated with a modified MOPP protocol whereby vincristine was replaced with vinblastine (MVPP). The overall response rate to MVPP was 25% with a median progression free survival of 15 days and a median overall survival of 45 days. MVPP at the prescribed doses resulted in modest and transient clinical benefit, but was well tolerated with no treatment delays or hospitalizations secondary to side effects. Given the minimal toxicity, dose intensification could be considered to improve clinical responses. 相似文献
12.
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
13.
Introduction: Regulatory T cells (Treg) are a naturally occurring population of T cells phenotypically identified by co‐expression of CD4 and the IL‐2 receptor (CD25). Theyplay a critical role in the control of tolerance and autoimmunity and have also been implicated in impairment of anti‐tumor responses. We hypothesized that levels of Treg would be higher in cancer‐bearing dogs than in normal dogs and that they would decrease with chemotherapy.
Methods: Serial PBMC were isolated from twenty cancer‐bearing dogs receiving either single‐agent doxorubicin or the Madison‐Wisconsin protocol. The following time points were studied: pre‐treatment, day 2, week 1, week 3, 3 months and 6 months after initial treatment. Ten age‐matched, normal dogs were also studied. PBMC were immunostained with directly conjugated antibodies to CD4, CD8, CD44 and IL‐2 receptor and then evaluated by flow cytometry.
Results: Low numbers of lymphocytes with the CD4+/IL‐2R+ phenotype were detectable in both normal and cancer‐bearing dogs. A statistically significant increase in the percentage of IL2‐R+/CD4+ T cells was observed in the cancer‐bearing dogs beginning two days after chemotherapy and persisting throughout treatment. The percentage of IL‐2R+/CD4+ T cells was also increased in pre‐treated cancer‐bearing dogs compared to control dogs.
Conclusion: The percentage of IL‐2R+/CD4+ T cells was generally higher in dogs with cancer than in healthy dogs. Unexpectedly, the percentage of IL‐2R+/CD4+ cells increased during chemotherapy which suggests that chemotherapy may exert immunosuppressive effects through a previously undescribed mechanism. The identity of these CD4+/IL‐2R+ T cells as true Treg awaits additional characterization studies. 相似文献
Methods: Serial PBMC were isolated from twenty cancer‐bearing dogs receiving either single‐agent doxorubicin or the Madison‐Wisconsin protocol. The following time points were studied: pre‐treatment, day 2, week 1, week 3, 3 months and 6 months after initial treatment. Ten age‐matched, normal dogs were also studied. PBMC were immunostained with directly conjugated antibodies to CD4, CD8, CD44 and IL‐2 receptor and then evaluated by flow cytometry.
Results: Low numbers of lymphocytes with the CD4+/IL‐2R+ phenotype were detectable in both normal and cancer‐bearing dogs. A statistically significant increase in the percentage of IL2‐R+/CD4+ T cells was observed in the cancer‐bearing dogs beginning two days after chemotherapy and persisting throughout treatment. The percentage of IL‐2R+/CD4+ T cells was also increased in pre‐treated cancer‐bearing dogs compared to control dogs.
Conclusion: The percentage of IL‐2R+/CD4+ T cells was generally higher in dogs with cancer than in healthy dogs. Unexpectedly, the percentage of IL‐2R+/CD4+ cells increased during chemotherapy which suggests that chemotherapy may exert immunosuppressive effects through a previously undescribed mechanism. The identity of these CD4+/IL‐2R+ T cells as true Treg awaits additional characterization studies. 相似文献
14.
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
15.
L. P. de Lorimier T. M. Fan S. Haney J. B. Grimm S. C. Charney C. A. Clifford 《Veterinary and comparative oncology》2005,3(1):39-39
Introduction: Megavoltage radiation is considered standard therapy for feline sinonasal neoplasia, but a paucity of published reports and the lack of a staging system based on advanced sectional imaging render accurate prognostication difficult. The aims of this retrospective study on feline sinonasal neoplasia were to adapt or develop a staging system based on advanced imaging, and to further define the prognosis with megavoltage radiation therapy.
Methods: Medical records were reviewed, and CT images were evaluated by a single radiologist (JBG) and staged using a modified system previously reported for dogs. Further follow‐up information was obtained by telephone interviews with the referring veterinarians or owners.
Results: Thirty‐six cats received megavoltage radiation for sinonasal neoplasia. Carcinomas (n = 17) and lymphomas (n = 16) were most common, followed by sarcomas (n = 3). A majority of immunophenotyped lymphomas were B‐cell (89%). Diagnostic CT images were available for review on 33 cats. The stage distribution was as follows: T1 (n = 3), T2 (n = 11), T3 (n = 5), T4 (n = 14). Lymphomas were more commonly T2 (n = 8) while a majority of carcinomas were T4 (n = 8). The median survival times have not yet been reached for any stage or disease subtype. The most common cause for euthanasia was local recurrence (15/19, 79%). Four cats that died of other causes lived between 1,124 and 2,322 days.
Conclusions: Feline sinonasal neoplasia is uncommon, with carcinomas and lymphomas being most frequently encountered. Megavoltage radiation therapy appears to offer improved quality and duration of life for most patients, despite advanced staged at diagnosis in a majority. 相似文献
Methods: Medical records were reviewed, and CT images were evaluated by a single radiologist (JBG) and staged using a modified system previously reported for dogs. Further follow‐up information was obtained by telephone interviews with the referring veterinarians or owners.
Results: Thirty‐six cats received megavoltage radiation for sinonasal neoplasia. Carcinomas (n = 17) and lymphomas (n = 16) were most common, followed by sarcomas (n = 3). A majority of immunophenotyped lymphomas were B‐cell (89%). Diagnostic CT images were available for review on 33 cats. The stage distribution was as follows: T1 (n = 3), T2 (n = 11), T3 (n = 5), T4 (n = 14). Lymphomas were more commonly T2 (n = 8) while a majority of carcinomas were T4 (n = 8). The median survival times have not yet been reached for any stage or disease subtype. The most common cause for euthanasia was local recurrence (15/19, 79%). Four cats that died of other causes lived between 1,124 and 2,322 days.
Conclusions: Feline sinonasal neoplasia is uncommon, with carcinomas and lymphomas being most frequently encountered. Megavoltage radiation therapy appears to offer improved quality and duration of life for most patients, despite advanced staged at diagnosis in a majority. 相似文献
16.
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
17.
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
18.
C.F. Saba S.D. Hafeman D.M. Vail D.H. Thamm 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(5):1058-1063
Background: The combination of lomustine, l -asparaginase, and prednisone (LAP) is an effective rescue treatment for canine lymphoma (LSA). In a previous study, we reported that remission was typically lost around the time l -asparaginase was discontinued.
Hypothesis: Use of l -asparaginase with each lomustine treatment will be well tolerated and efficacious as a rescue therapy for canine LSA.
Animals: Forty-eight client-owned dogs with cytologically confirmed multicentric LSA whose disease had relapsed after a cyclophosphamide, doxorubicin, vincristine, and prednisone-based chemotherapy protocol were included.
Methods: Lomustine was administered orally at 3-week intervals, concurrently with subcutaneous or intramuscular l -asparaginase for a total of 5 doses or until disease progression. Prednisone was administered at a tapering dose for the duration of the protocol.
Results: The overall response rate (ORR) for dogs treated with this protocol was 77%, with 65% achieving a complete response (CR). The median time to progression (TTP) was 70 days. Based on loose comparison, these findings are not significantly different from our previously reported historical control. The actual CCNU dosage administered did not affect response rate or remission duration.
Conclusions/Clinical Importance: These findings support previous data concluding that the LAP protocol is a viable rescue treatment option for dogs with LSA. However, results from this study suggest that continued use of l -asparaginase with each lomustine treatment does not significantly increase remission duration and toxicity appears greater. 相似文献
Hypothesis: Use of l -asparaginase with each lomustine treatment will be well tolerated and efficacious as a rescue therapy for canine LSA.
Animals: Forty-eight client-owned dogs with cytologically confirmed multicentric LSA whose disease had relapsed after a cyclophosphamide, doxorubicin, vincristine, and prednisone-based chemotherapy protocol were included.
Methods: Lomustine was administered orally at 3-week intervals, concurrently with subcutaneous or intramuscular l -asparaginase for a total of 5 doses or until disease progression. Prednisone was administered at a tapering dose for the duration of the protocol.
Results: The overall response rate (ORR) for dogs treated with this protocol was 77%, with 65% achieving a complete response (CR). The median time to progression (TTP) was 70 days. Based on loose comparison, these findings are not significantly different from our previously reported historical control. The actual CCNU dosage administered did not affect response rate or remission duration.
Conclusions/Clinical Importance: These findings support previous data concluding that the LAP protocol is a viable rescue treatment option for dogs with LSA. However, results from this study suggest that continued use of l -asparaginase with each lomustine treatment does not significantly increase remission duration and toxicity appears greater. 相似文献
19.
P.C. Griessmayr S.E. Payne J.E. Winter L.G. Barber F.S. Shofer 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(6):1227-1231
Background: Multidrug resistance is the most common cause of treatment failure in dogs with multicentric lymphoma. 5-(3,3-Dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) is an atypical alkylator used as standard treatment in human Hodgkin's lymphoma, and has been effective in combination treatment to treat resistant lymphoma in dogs. However, no data are available on the use of DTIC as a single agent in the treatment of relapsed canine lymphoma.
Hypothesis: Single-agent DTIC is effective and safe in treating dogs with lymphoma that relapsed or failed to respond to previous chemotherapy.
Animals: Forty client-owned dogs with relapsed lymphoma.
Methods: Dogs were eligible for the retrospective study if they had a histologically or cytologically confirmed diagnosis of lymphoma and had relapsed. Dogs received DTIC (800–1,000 mg/m2 every 2–3 weeks as a 4–5-hour IV infusion) and were evaluated for response rate and duration. Hematologic and gastrointestinal toxicity was assessed.
Results: The overall response rate for dogs being treated with DTIC was 35% (14 dogs) with a median progression-free interval of 43 days. Thirteen dogs had a partial response and 1 dog had a complete response. Stable disease was achieved in 3 dogs. Mild gastrointestinal toxicity was reported in 3 dogs posttreatment. Thrombocytopenia was the principal toxicity observed 7–14 days after the treatment. Treatments were delayed because of thrombocytopenia.
Conclusions: DTIC, when used alone, is effective in the treatment of dogs with relapsed lymphoma. 相似文献
Hypothesis: Single-agent DTIC is effective and safe in treating dogs with lymphoma that relapsed or failed to respond to previous chemotherapy.
Animals: Forty client-owned dogs with relapsed lymphoma.
Methods: Dogs were eligible for the retrospective study if they had a histologically or cytologically confirmed diagnosis of lymphoma and had relapsed. Dogs received DTIC (800–1,000 mg/m
Results: The overall response rate for dogs being treated with DTIC was 35% (14 dogs) with a median progression-free interval of 43 days. Thirteen dogs had a partial response and 1 dog had a complete response. Stable disease was achieved in 3 dogs. Mild gastrointestinal toxicity was reported in 3 dogs posttreatment. Thrombocytopenia was the principal toxicity observed 7–14 days after the treatment. Treatments were delayed because of thrombocytopenia.
Conclusions: DTIC, when used alone, is effective in the treatment of dogs with relapsed lymphoma. 相似文献
20.
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