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Background: Electrochemotherapy (ECT) couples the administration of anticancer drugs with the delivery of electric pulses that increase the drug uptake through the cell membranes, resulting in an improved efficacy. Hypothesis: To evaluate the tolerability and efficacy of cisplatin (CDDP) as an ECT agent to prevent recurrence of incompletely resected mast cell tumors (MCTs). Animals: Thirty‐seven dogs. Methods: Prospective study recruiting dogs with incompletely excised MCTs as confirmed by surgeon and pathology reports. After debulking, the tumor bed and margins were infiltrated with CDDP, and then exposed to trains of biphasic electrical pulses under sedation. Five minutes after the injection of the chemotherapy agent, sequences of 8 biphasic pulses lasting 50 + 50 μs each, were delivered in bursts of 1,300 V/cm for sclerosed and of 800 V/cm for exposed lesions, with caliper or needle array electrodes, respectively. A second session was performed 1 or 2 weeks later based on clinical considerations. Results: The treatment was well tolerated with minimal adverse effects. Twenty‐nine dogs had no evidence of recurrence over the 6‐year study period, 6 had tumor recurrence, 1 died of multiple cutaneous MCTs, and 1 died of unrelated causes. The estimated median time to recurrence was 1,200 days. Recurrence was not observed among the long‐term (>1 year) treated dogs. Conclusions and Clinical Importance: ECT with CDDP appears effective in the treatment of incompletely resected MCT in dogs and could be a useful addition to the current options based on its low cost, limited toxicity, and ease of administration.  相似文献   
2.
Mast cell tumor (MCT) is one of the most common tumors of dogs. Some affected dogs develop multiple cutaneous tumors in various locations over months to years. In these cases, it is not clear whether the tumors have arisen de novo, or if each tumor represents a recurrence of the previously excised original tumor (ie, distant metastasis). We used the presence of an internal tandem duplication (ITD) in c-kit to demonstrate that in 2 dogs with recurrent cutaneous MCT that had developed over 1-2 years, each recurrent MCT tumor possessed an identical ITD when compared to the original MCT, indicating that the multiple tumors were clonal in origin. This study demonstrates that similar to the situation in humans, specific somatic mutations identified in oncogenes found in canine neoplasms can be used to provide evidence of tumor clonality.  相似文献   
3.
BACKGROUND: Mast cell tumors (MCTs) with bone marrow (BM) involvement are poorly documented in dogs and are associated with a poor prognosis. Successful treatment strategies have not been described. HYPOTHESIS: Clinicopathologic findings of affected dogs are not specific. Administration of lomustine or imatinib is beneficial. ANIMALS: Fourteen dogs with MCT and BM involvement. METHODS: Clinical and laboratory evaluations were performed in each dog on admission and during follow-up. All dogs received prednisone. Additionally, 8 dogs received lomustine and 3 dogs received imatinib. Imatinib was administered if tumor-associated tyrosine kinase KIT was aberrant. RESULTS: On admission, 11 dogs had a single cutaneous nodule and 3 dogs had multiple nodules. Involvement of regional lymph nodes, liver, or spleen was observed in each dog. BM infiltration with mast cells (MCs) was observed in all dogs. On CBC, nonregenerative anemia, leukopenia, or thrombocytopenia was common. Four dogs had circulating MCs. Increased alkaline phosphatase or alanine transferase activity was observed in 12 and 10 dogs, respectively. Treatment with lomustine induced partial remission in 1 of 8 dogs. Median survival time was 43 days (range, 14-57). Dogs on imatinib experienced complete remission. Two dogs survived for 117 and 159 days, and the third was alive after 75 days. Dogs treated symptomatically did not improve and were euthanized after 1, 14, and 32 days. CONCLUSIONS AND CLINICAL IMPORTANCE: A combination of clinical and laboratory evaluation helps in identifying dogs with MCT and BM infiltration. Administration of lomustine is not helpful in affected dogs. The beneficial effect of imatinib warrants further investigation.  相似文献   
4.

Background

Mutation analysis of proto‐oncogene c‐kit (c‐kit) is advisable before starting treatment with tyrosine kinase inhibitors in dogs with mast cell tumor (MCT), including those with metastatic disease. Testing is usually performed on primary tumors, assuming that c‐kit mutation status does not change in metastasis.

Hypothesis/Objectives

To give an insight into the mutational processes and to make a recommendation on the use of c‐kit mutational analysis in the clinical setting.

Animals

Twenty‐one client‐owned dogs with metastatic MCT.

Methods

Dogs undergoing resection or biopsy for both primary and matched metastatic MCT were prospectively enrolled. Total RNA or DNA was extracted from primary MCT and corresponding metastases. Exons 8, 9, and 11 were amplified by PCR and sequenced. Genetic features between primary MCT and metastases were compared. Their correlation with clinicopathologic features was investigated.

Results

Concordance (mutated or wild‐type) of mutational status, evaluable in 21 primary and matched metastatic (20 nodal and 1 splenic) MCTs, was 100%. Three new c‐kit mutations were identified. No significant correlation was detected between c‐kit mutation and clinicopathologic features.

Conclusions and Clinical Importance

Proto‐oncogene c‐kit mutational status is conserved between any primary and its matched secondary tumor, suggesting that both can be used for c‐kit mutational testing. Targeted therapies might be also used to treat metastatic disease.  相似文献   
5.
Forty-one dogs with mast cell tumors (MCTs) were treated with oral prednisone and injectable vinblastine (VBL), both in the adjuvant setting (23 dogs) and in dogs with gross disease (18 dogs). Adverse effects were noted in 20% (8/41) of the patients, usually after the 1st dose of VBL. Adverse effects were considered mild in 6, and severe, necessitating treatment discontinuation, in 2 (5%). Overall response rate in the evaluable dogs with gross disease was 47% (7/15), consisting of 5 complete responses and 2 partial responses. Median response duration was 154 days (24 to >645 days). As adjuvant therapy to incomplete surgical resection, prednisone and VBL conferred a 57% 1- and 2-year disease-free rate. Median survival time (MST) for the entire patient population was not reached with a median follow-up of 573 days; however, the MST for dogs with grade III MCT was 331 days, with 45% of dogs alive at 1 and 2 years. This is an apparent improvement over historical survival data employing surgery alone. Upon univariate analysis, significant prognostic factors (P < .05) for survival included presence of a locally recurrent tumor, presence of gross disease, argyrophilic nucleolar organizer region frequency, lymph node status, histologic grade, previous chemotherapy, and ulceration of the tumor. Similar criteria were significant when analyzed for time to treatment failure. Response to therapy was also predictive of survival in the gross disease group. Upon multivariate analysis, histologic grade (P = .012) and presence of a locally recurrent tumor (P < .001) were significant factors for survival.  相似文献   
6.
Plasma histamine concentrations (PHCs) were measured serially over 9 months or until death in 11 dogs with mast cell tumors (MCTs). Eight dogs had grossly visible disease and the other 3 dogs had microscopic disease. Initial PHCs in the dogs with gross disease were significantly higher than PHCs in healthy dogs (median, 0.73 ng/mL and 0.19 ng/mL respectively; P < .009), whereas initial PHCs in dogs with microscopic disease showed no difference from controls. Seven dogs subsequently had progressive increases in PHC, and developed hyperhistaminemia (median, 14.0 ng/mL; range, 5.11-30.1 ng/nL). These 7 dogs died from MCTs, and 1 had general weakness with rapid lysis of a large tumor burden after radiation therapy. PHCs of the other 4 dogs were less than 1 ng/mL during the study. These 4 dogs were still alive with adequate control of the tumor at the conclusion of the study. Four of the 11 dogs initially had gastrointestinal (G1) signs, which abated soon after administration of histamine-2 (H-2) blockers. No significant difference was found between PHCs in dogs with GI signs and those without GI signs (median, 0.86 ng/mL and 0.35 ng/mL. respectively). Thereafter, 7 dogs had serious GI complications for which H-2 blocker therapy was ineffective. PHCs in these 7 dogs were extremely high (median, 12.2 ng/mL; range, 3.42-30.1 ng/nL). Results of this study demonsrated that PHC was one factor related to disease progression, and indicated that marked hyperhistaminemia was associated with the GI signs refractory to H-2 blocker therapy in dogs with MCTs.  相似文献   
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