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1.
Efficacy of mitoxantrone against various neoplasms in dogs   总被引：2，自引：0，他引：2  
One hundred twenty-six dogs with histologically confirmed, measurable malignant tumors were evaluated in a prospective study to determine the response to the antineoplastic drug mitoxantrone. Ninety-five dogs had been refractory to one or more treatment modalities (surgery, n = 57; chemotherapy other than mitoxantrone, n = 37; radiation, n = 4; whole body hyperthermia, n = 1). The extent of neoplastic disease was determined immediately before each dose of mitoxantrone was administered (1 to 10 doses, 2.5 to 5 mg/m2 of body surface area, IV) 21 days apart. Each dog was treated with mitoxantrone until the dog developed progressive disease or until the dog's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. A partial or complete remission (greater than 50% volume reduction) was obtained in 23% (29/126) of all dogs treated. Tumors in which there was a partial or complete remission included lymphoma (11/32), squamous cell carcinoma (4/9), fibrosarcoma (2/9), thyroid carcinoma (1/10), transitional cell carcinoma (1/6), mammary adenocarcinoma (1/6), hepatocellular carcinoma (1/4), renal adenocarcinoma (1/1), rectal carcinoma (1/1), chondrosarcoma (1/2), oral malignant melanoma (1/12), cutaneous malignant melanoma (1/1), myxosarcoma (1/1), mesothelioma (1/1), and hemangiopericytoma (1/1). Our results indicated that mitoxantrone induces measurable regression in various malignant tumors in dogs.  相似文献   
2.
Interleukins: Biological Properties and Therapeutic Potential   总被引：1，自引：0，他引：1  
Interleukins are biologically active glycoproteins derived primarily from activated lymphocytes and macrophages. Tremendous insight into the biochemical and biological properties of interleukins has been gained with advances in recombinant DNA technology, protein purification, and cell-culture techniques. The biological properties of interleukins include induction of T-lymphocyte activation and proliferation, augmentation of neutrophil, macrophage, and T-lymphocyte cytotoxicity, and promotion of B lymphocyte and multilineage bone marrow stem-cell precursor growth and differentiation. Interleukins may play a role in the pathogenesis of several important diseases. Interleukin therapy is likely to play an important role in the treatment of cancer, infectious diseases, and immunodeficiency syndromes.  相似文献   
3.
Fifteen dogs were given doxorubicin, IV, at a dosage of 30 mg/m2 of body surface. A commercially available biological extract of Serratia marcescens (BESM) was administered SC to 9 of these dogs (0.04 mg/kg of body weight every third day, n = 2; 0.08 mg/kg every other day, n = 2; and 0.08 mg/kg daily, n = 5), beginning the day after administration of doxorubicin, in an attempt to find an optimal dosage and schedule of administration of BESM to reduce the duration and severity of chemotherapy-induced myelosuppression. Nine additional dogs were randomized into 3 groups of 3 dogs to receive 1 of the following dosages of BESM SC: 0.08, 0.16, and 0.32 mg/kg. Serum was harvested immediately prior to treatment and at 2, 4, 6, 8, 12, 24, 48, and 72 hours from this latter group of dogs for subsequent analysis of canine granulocyte colony-stimulating factor (G-CSF) by enzyme immunoassay. Increasing the dosage and schedule of administration of BESM reduced the duration and severity of doxorubicin-induced myelosuppression. Neutrophil counts of the group of dogs given BESM daily at a dosage of 0.08 mg/kg and the controls were evaluated statistically. The neutrophil count increased significantly (P < 0.05) above pretreatment values in BESM-treated dogs after day 7. Median neutrophil counts of the BESM-treated dogs were never significantly lower than pretreatment values, whereas the median counts of the dogs treated with doxorubicin alone were significantly below normal for 6 days (days 7-12).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
4.
Increased numbers of tumour‐associated macrophages correlate with rapid tumour growth and metastasis in tumours. Thus, macrophage depletion has potential as a novel cancer therapy and positive responses have been reported in rodent tumour models. To investigate the effectiveness of this approach in dogs with cancer, we evaluated the effects of the macrophage‐depleting agent liposomal clodronate (LC) in dogs with soft‐tissue sarcoma (STS). To this end, we conducted a clinical trial of LC therapy in 13 dogs with STS. Repeated LC administration was well tolerated clinically. Preliminary examination of tumour biopsy sets from 5 of the 13 dogs demonstrated that the density of CD11b+ macrophages was significantly decreased after LC treatment. Circulating concentrations of interleukin‐8 were also significantly reduced. These preliminary studies are the first to suggest that LC can be used as a systemic macrophage‐depleting agent in dogs to reduce numbers of tumour‐associated macrophages.  相似文献   
5.
BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor in dogs. At present, conventional adjuvant chemotherapy provides only a modest survival benefit for treated dogs. Continuous oral administration of low-dose chemotherapy (LDC) has been suggested as an alternative to conventional chemotherapy protocols. Therefore, we evaluated the safety and effectiveness of LDC using a combination of cyclophosphamide, etoposide, and piroxicam as adjuvant therapy for dogs with stage II HSA. HYPOTHESIS: We hypothesized that oral adjuvant therapy with LDC could be safely administered to dogs with HSA and that survival times would be comparable to those attained with conventional doxorubicin (DOX) chemotherapy. ANIMALS: Nine dogs with stage II splenic HSA were enrolled in the LDC study. Treatment outcomes were also evaluated retrospectively for 24 dogs with stage II splenic HSA treated with DOX chemotherapy. METHODS: Nine dogs with stage II splenic HSA were treated with LDC over a 6-month period. Adverse effects and treatment outcomes were determined. The pharmacokinetics of orally administered etoposide were determined in 3 dogs. Overall survival times and disease-free intervals were compared between the 9 LDC-treated dogs and 24 DOX-treated dogs. RESULTS: Dogs treated with LDC did not develop severe adverse effects, and long-term treatment over 6 months was well-tolerated. Oral administration of etoposide resulted in detectable plasma concentrations that peaked between 30 and 60 minutes after dosing. Both the median overall survival time and the median disease-free interval in dogs treated with LDC were 178 days. By comparison, the overall survival time and disease-free interval in dogs treated with DOX were 133 and 126 days, respectively. CONCLUSIONS: Continuous orally administered LDC may be an effective alternative to conventional high-dose chemotherapy for adjuvant therapy of dogs with HSA.  相似文献   
6.
One hundred twenty-nine dogs with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of the new dihydroxyquinone derivative of anthracene, mitoxantrone, which was administered IV at 21-day intervals at dosages ranging from 2.5 to 5 mg/m2 body surface area. Each dog was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the dog died, whichever came first. The number of dogs in each evaluation period were as follows: 1 dose (n = 129), 2 doses (n = 82), 3 doses (n = 43), 4 doses (n = 26), 5 doses (n = 19), 6 doses (n = 9), 7 doses (n = 6), 8 doses (n = 5), 9 doses (n = 3), and 10 doses (n = 1). The most common signs of toxicosis were vomiting, diarrhea, anorexia, and sepsis secondary to myelosuppression. None of the dogs died of complications resulting from mitoxantrone treatment. Dogs with signs of toxicosis during the 21-day interval from administration of the first dose of mitoxantrone were 95 times (P = 0.003) more likely to develop signs of toxicosis during the 21-day interval from the second dose of mitoxantrone. Similarly, dogs that developed signs of toxicosis during the 21-day interval from the administration of the second dose were 34 times (P less than 0.001) more likely to develop signs of toxicosis during the 21-day interval from the administration of the third dose. With each 1 mg/m2 increase in mitoxantrone, the odds of developing signs of toxicosis increased by 5.9 fold (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
7.
BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.  相似文献   
8.
BACKGROUND: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor of dogs. At present, adjuvant chemotherapy is the only proven effective treatment for dogs with HSA, though the benefits from chemotherapy are modest. Administration of immunotherapy together with chemotherapy has also been reported to improve survival in dogs with HSA. Therefore, we evaluated safety and immunologic responses to a novel tumor vaccine administered together with doxorubicin chemotherapy in dogs with different stages of HSA. HYPOTHESIS: That tumor vaccination could be safely and effectively combined with doxorubicin chemotherapy for treatment of dogs with HSA. ANIMALS: Twenty-eight dogs with various stages of HSA were enrolled in the study. METHODS: The HSA vaccine was prepared with lysates of allogeneic canine HSA cell lines mixed with an adjuvant composed of liposome-DNA complexes. Dogs received a series of 8 immunizations administered over a 22-week period, and most also received chemotherapy. Clinical adverse effects were noted, immune responses were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, and survival times were calculated. RESULTS: The most common adverse effects observed in vaccinated dogs also treated with doxorubicin chemotherapy were diarrhea and anorexia. Vaccinated dogs were found to mount strong humoral immune responses against a control antigen and, most dogs also mounted antibody responses against canine HSA cells. Thirteen dogs with stage II splenic HSA that received the tumor vaccine plus doxorubicin chemotherapy had an overall median survival time of 182 days. CONCLUSIONS: We conclude that an allogeneic tumor lysate vaccine is safe in dogs with HSA and can elicit humoral immune responses in dogs that are receiving concurrent doxorubicin chemotherapy.  相似文献   
9.
Immunotherapies targeting checkpoint molecule programmed cell death 1 (PD‐1) protein were shown to be effective for treatment of non‐Hodgkin lymphoma in people, but little is known about the expression of PD‐1 or its ligand PD‐L1 by canine lymphoma. Therefore, flow cytometry was used to analyse expression of PD‐1 and PD‐L1 in canine lymphoma, using fine‐needle aspirates of lymph nodes from 34 dogs with B cell lymphoma (BCL), 6 dogs with T cell lymphoma (TCL) and 11 dogs that had relapsed. Furthermore, fine‐needle aspirates were obtained from 17 healthy dogs for comparison. Lastly, the impact of chemotherapy resistance on expression of PD‐1 and PD‐L1 was assessed in vitro. These studies revealed increased expression of PD‐L1 by malignant B cells compared to normal B cells. In the case of TCL, tumour cells and normal T cells both showed low to negative expression of PD‐1 and PD‐L1. In addition, tumour infiltrating lymphocytes from both BCL and TCL had increased expression of both PD‐1 and PD‐L1 expression compared to B and T cells from lymph nodes of healthy animals. In vitro, chemotherapy‐resistant BCL and TCL cell lines exhibited increases in both PD‐1 and PD‐L1 expression, compared to non‐chemotherapy selected tumour cells. These findings indicate that canine lymphomas exhibit upregulated checkpoint molecule expression, though the impact of checkpoint molecule expression on tumour biological behaviour remains unclear.  相似文献   
10.
Background: Regulatory T cells (Treg) have been shown to suppress antitumor immunity and often are increased in humans and rodents with cancer. However, Tregs have not been well studied in dogs with cancer and it is not known if certain tumor types are associated with increased Tregs.
Hypothesis: We hypothesized that Treg percentages would be increased in dogs with cancer and that Treg percentages would be higher in dogs with certain types of cancer.
Animals: The percentages and numbers of Tregs and nonregulatory T cells and B cells were assessed in 34 dogs with cancer and 9 age-matched control dogs. Dogs evaluated included 14 dogs with sarcoma, 7 dogs with carcinoma, 7 dogs with lymphoma, and 6 dogs with mast cell tumor.
Methods: Numbers and percentages of Tregs, CD4+, and CD8+ T cells and B cells were determined using flow cytometry and compared between control dogs and dogs with cancer.
Results: The percentage of Tregs was significantly increased overall in dogs with cancer compared with control dogs. When tumor types were compared, Treg percentages were significantly increased in dogs with carcinoma. The Treg/CD8 T cell ratio was significantly higher in dogs with cancer compared with control dogs and was also significantly increased in 2 dogs with T-cell lymphoma.
Conclusions: Treg percentages in blood were increased in dogs with cancer, particularly in dogs with carcinoma. The Treg/CD8 ratio also identified tumor-specific abnormalities in dogs with cancer. These findings indicate that tumor-specific factors may affect Tregs in dogs.  相似文献   
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