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1.
Background: Low‐dose, continuous (metronomic) chemotherapy improves tumor control by inhibiting tumor angiogenesis and suppressing regulatory T cells (Treg) in mice and humans. The effects of metronomic chemotherapy on Treg and tumor angiogenesis in dogs has not been investigated previously. Objective: To determine whether metronomic cyclophosphamide (CYC) therapy decreases Treg or exhibits antiangiogenic activity or both in dogs with soft tissue sarcoma (STS). We hypothesized that Treg numbers would be increased in dogs with STS and that continuous dosing of CYC would decrease Treg in a dose‐dependent manner, as well as exhibit antiangiogenic activity. Animals: Eleven client‐owned dogs with grade I or II STS. Twenty‐one healthy dogs were used as controls. Methods: Prospective, open, clinical trial. Dogs with STS were enrolled in 2 dose cohorts and administered CYC at 12.5 or 15 mg/m2 PO once daily for 28 days. Whole blood and tumor biopsy specimens were obtained on days 0, 14, and 28 to assess changes in T lymphocyte subsets by flow cytometry and tumor microvessel density (MVD), respectively. Results: Administration of CYC at 12.5 mg/m2/d significantly decreased the number of Treg from days 0 to 28, but there was no change in the percentage of Treg or tumor MVD. In dogs that received CYC at 15.0 mg/m2/d, both the number and percent of Treg as well as tumor MVD were significantly decreased over 28 days. Conclusions: CYC administered at 15 mg/m2/d should be used in further studies examining the antitumor properties of low‐dose CYC in dogs.  相似文献   

2.
Combretastatin A4 ‐Phosphate (CA4P ) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100 mg m?2. At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low‐grade neutropenia was observed in all dogs. Doses of 75 and 100 mg m?2 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m?2, low‐grade hypertension and high‐grade neurotoxicity were also observed. In healthy dogs, doses up to 75 mg m?2 seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m?2, although transient, does not invite to use this dose in canine oncology patients.  相似文献   

3.
Objective: To evaluate lymphocyte populations in stifle synovium and synovial fluid of dogs with degenerative cranial cruciate ligament rupture (CCLR). Study Design: Prospective clinical study. Animals: Dogs (n=25) with stifle arthritis and CCLR, 7 dogs with arthritis associated with cartilage degeneration (osteoarthritis [OA]), and 12 healthy Beagle dogs with intact CCL. Methods: Arthritis was graded radiographically in CCLR dogs. After collection of joint tissues, mononuclear cells were isolated and subsequently analyzed using flow cytometry for expression of CD3, CD4, CD8, and CD21. Results: The proportions of CD4+ T helper lymphocytes, CD8+ cytotoxic T lymphocytes, and CD3+CD4?CD8? T lymphocytes were increased in synovium from dogs with CCLR compared with synovium from healthy Beagle dogs (P<.05). The proportion of CD3+CD4?CD8? T lymphocytes in synovial fluid was increased in dogs with CCLR compared with dogs with OA (P<.05). In dogs with CCLR, the proportion of CD3+CD4?CD8? T lymphocytes in synovial fluid was inversely correlated with radiographic arthritis (SR=?0.68, P<.005). Conclusion: Lymphocytic inflammation of stifle synovium and synovial fluid is an important feature of the CCLR arthropathy. Lymphocyte populations include T lymphocytes expressing CD4 and CD8, and CD3+CD4?CD8? T lymphocytes. Presence of CD3+CD4?CD8? T lymphocytes was associated with development of stifle synovitis. Further work is needed to fully identify the phenotype of these cells.  相似文献   

4.
The study hypothesis is that higher doses of metronomic (low‐dose) chlorambucil will improve outcome without significantly worsening adverse events (AE). Retrospectively, 88 dogs were screened to assess for tolerability and response to chlorambucil utilizing retrospective and prospective data sets, comparing metronomic oral daily doses 4, 6 and 8 mg m2. There were 78 and 70 dogs in the tolerability and efficacy portions, respectively. The severity of gastrointestinal (GI) AE was significantly worse, and time to development of GI events was significantly shorter at 6 mg m2 than at 4 mg m2 (both P < 0.001). Chlorambucil was discontinued earlier in the dogs treated at the 6 mg m2 doses than in the dogs treated at 4 mg m2 (P = 0.015). Thrombocytopenia occurred significantly earlier at 8 mg m2 than at 4 mg m2 (P = 0.017). Higher doses of metronomic (low‐dose) chlorambucil did not provide improved responses and were associated with more AE.  相似文献   

5.
We investigated the distribution of B and T cells in the peripheral blood of haematologically inconspicuous (non‐persistent lymphocytotic, PL?) cattle infected with the bovine leukaemia virus (BLV). Flow cytometric data were obtained from six PL? cattle and compared with six age‐matched animals with persistent lymphocytosis (PL+) and five non‐infected healthy controls (BLV?). In the PL? group, the percentage and number of surface immunoglobulin‐positive (sIg+) B cells were significantly reduced. Whereas in BLV? cattle, about 40% of the peripheral blood lymphocytes (PBL) were sIg+ and 24% were sIgM+ B cells. In the PL? group, less than 20% of the PBL were sIg+ and sIgM+ B cells. Only 5% of the PBL co‐expressed sIgM+ and CD5+ versus 16% in BLV?. This decrease was persistent over 3 years and predominantly affected: (i) B cells that did not express sIgM; (ii) sIgM+ B cells co‐expressing CD5 and CD11b; and (iii) equally both λ‐ and κ‐type light chain B‐cell subpopulations. In contrast, the number of all circulating lymphocytes, CD5? and CD11b? sIgM+ B cells and CD2+ T cells did not differ. In PL+ animals, about 75% of the PBL were sIgM+CD5+ B cells. These cells were of polyclonal origin, as light chains of the λ‐ and κ‐type were expressed in a ratio of 4:1 (57.7% of PBL λ+, 14% κ+) as in BLV? animals (33.6% of PBL λ+, 8.7% κ+). In PL+ cattle the absolute number of B‐cells and, therefore, their relative percentage is significantly increased. For this reason, even in case of absolutely increased T‐cell numbers, the relative percentage of T‐cells could be lower than in normal controls. The cause for the observed B cell decrease in PL? cattle is unknown, but it can be assumed that cytotoxic T cells are involved in this B‐cell lymphopenia.  相似文献   

6.
Prognosis for unresectable canine malignant melanoma (MM) is typically poor, and therapeutic approaches remain largely palliative. A bi‐institutional trial was conducted to compare efficacy and safety of radiation therapy (RT) and RT with post‐radiation temozolomide in dogs with chemotherapy‐naïve, measurable MM. RT consisted of 5 × 6 Gy fractions over 2.5 weeks. Dogs whose owners wished to pursue chemotherapy received adjuvant oral temozolomide (60 mg m?2 for 5 days every 28 days). Fifteen dogs were treated with RT only (Group 1) and 12 dogs subsequently received temozolomide (Group 2). Overall response rate was similar between Group 1 (86.7%) and Group 2 (81.1%). Median time to progression (TTP) was significantly longer in Group 2 (205 days) compared to Group 1 (110 days; p = 0.046). Survival time was not significantly different between groups. Both treatments were well tolerated. Post‐radiation temozolomide has a good safety profile, and may improve TTP in MM when compared to coarse fractionated RT.  相似文献   

7.
Maximally tolerated dose (MTD) and metronomic dose chemotherapeutic approaches alter the immune system and the angiogenic process in different yet potentially complementary ways. A combination of MTD doxorubicin (MTD‐DOX) and metronomic cyclophosphamide (mCTX) protocol was evaluated for safety and effect on circulating regulatory T (Treg) cells. We found that mCTX can be safely administered with MTD‐DOX in tumour‐bearing dogs. Both combination DOX/mCTX and single‐agent DOX resulted in significant depletions of circulating lymphocytes throughout the chemotherapy cycle without apparent selectivity for Tregs. The indiscriminant lymphocyte depletions were similar between dogs randomized to receive DOX and dogs randomized to receive DOX/mCTX, suggesting this effect is because of DOX alone. These findings may have implications as to the therapeutic benefit (or lack thereof) of concurrent combination MTD and metronomic protocols. Future investigations are required to determine the effects and indeed the efficacy of concurrent versus sequential applications of MTD and metronomic chemotherapy protocols.  相似文献   

8.
Background: Metronomic chemotherapy with alkylating agents has been shown to suppress tumor angiogenesis and prevent tumor recurrence in some settings. The use of adjuvant lomustine (1‐(2‐chloroethyl)‐3‐cyclohexyl‐1‐nitrosourea) administered in a metronomic fashion has not been evaluated in dogs. Hypothesis: Oral metronomic administration of lomustine will be well tolerated in dogs with spontaneously occurring malignant neoplasms. Animals: Eighty‐one dogs with naturally occurring primary or metastatic tumors received metronomic administration of lomustine. Methods: Dogs were enrolled prospectively after cytological or histological diagnosis of a tumor that was unresectable, incompletely resected, refractory to chemotherapy, or metastatic. Dogs received once daily lomustine (2.84 mg/m2 PO). End points of the trial were clinical, hematologic, or biochemical evidence of toxicosis, tumor progression, or death. Results: Starting dosage (median) was 2.84 mg/m2 PO daily and treatment duration was 98 days (median, range, 1–770 days). The drug was discontinued in 22 dogs because of toxicoses. Toxicoses occurred in 13 dogs with gastrointestinal toxicosis, 4 dogs with thrombocytopenia, 3 dogs with increased alanine transaminase, 1 dog with neutropenia, and 1 dog with progressive azotemia. Eight dogs developed some degree of azotemia during treatment. Hepatotoxicosis was observed at a median of 265 days in 11 dogs. Thrombocytopenia was identified at a median of 432 days of administration. Conclusions and Clinical Importance: In dogs with metastatic or terminal neoplasms without renal compromise, metronomic administration of lomustine was well tolerated. This can provide a treatment strategy for dogs that do not have other standard‐care treatment options, and warrants evaluation in primary therapy.  相似文献   

9.
Combining conventional cytotoxic maximum tolerated dose (MTD) chemotherapy with low‐dose metronomic and/or anti‐angiogenic agents is a exciting area of oncologic research. The objective of this study was to establish the MTD, safety and adverse event (AE) profile of 1 such drug combination. This prospective phase I dose‐finding clinical trial assumed an open‐label 3 + 3 cohort design. Client‐owned dogs with 1 or more cytologically and/or histologically confirmed and macroscopically measurable, naive or recurrent, malignant tumours, were enrolled. No preference for tumour histology, grade or stage was expressed. Toceranib was administered at a dose of 2.75 mg kg?1 by mouth (PO) every other day (EOD), and carboplatin administered intravenously (IV) every 21 days at a starting dose of 200 mg m?2. A total of 25% dose escalation was proposed for carboplatin, to a maximum of 300 mg m?2. AEs were graded according to the Veterinary Cooperative Oncology Group's common terminology criteria for AEs (VCOG‐CTCAE). Grade 3 haematologic or gastrointestinal AEs were nominated dose‐limiting. Response to therapy was evaluated according to the VCOG's revised RECIST criteria. Eleven dogs were enrolled. Tumour histologies included sinonasal carcinoma, osteosarcoma, thyroid carcinoma, melanoma and apocrine gland anal sac adenocarcinoma. MTDs of carboplatin and toceranib were identified as 200 mg m?2 IV every 21 days and approximately 2.75 mg kg?1 PO EOD, respectively. The dose‐limiting toxicity was neutropenia. Two dogs experienced a partial response, and 6 maintained stable disease. Combination carboplatin and toceranib chemotherapy was well‐tolerated. Clinical benefit was observed in most cases. This protocol warrants further investigation in phase II/III trials.  相似文献   

10.
Canine T‐cell lymphoma (TCL) encompasses a heterogeneous group of diseases with variable clinical presentation, cytomorphology, immunophenotype, and biologic behaviour. The most common types of TCL in dogs involving peripheral lymph nodes include indolent T‐zone lymphoma (TZL) and biologically aggressive peripheral T‐cell lymphoma (PTCL). TCL phenotypes can be categorized by expression of the surface antigen molecules CD4 and CD8. The majority of TCL cases are CD4+, with far fewer cases being CD8+ or CD4? CD8?. The clinical features of CD4+ TCLs have been previously described. The less common TCL phenotypes, however, are poorly characterized with little to no information about prognosis. In this retrospective study, we describe and correlate the presenting clinical signs, flow cytometry, and outcomes of 119 dogs diagnosed with nodal, non‐TZL, CD8+ or CD4? CD8? TCL by flow cytometry. Skin lesions present at the time of diagnosis were more commonly observed in the CD8+ TCL group. Mediastinal enlargement and/or hypercalcemia were more commonly seen in the CD4? CD8? TCL group. Dogs with either CD8+ or CD4? CD8? TCLs had aggressive clinical disease with median overall survival (OS) times of 198 days and 145 days, respectively. In both groups, neoplastic cell size determined by flow cytometry ranged from small to large, and large cell size was associated with shorter OS times (median OS = 61 days). Cases classified as small cell had a median OS of 257 days. Expression levels of major histocompatibility complex (MHC) class II and CD5 were highly variable among cases but were not prognostically significant in this group of patients.  相似文献   

11.
This study characterizes T‐ and B‐lymphocyte responses in the peripheral blood and lesional skin of dogs with immunomodulatory‐responsive lymphocytic–plasmacytic pododermatitis (ImR‐LPP), a term previously proposed to denote a subpopulation of dogs with idiopathic pododermatitis. T‐cell (CD3+, CD4+ and CD8+) and B‐cell (CD21+) counts were significantly increased in both the epidermis and dermis of lesional ImR‐LPP skin compared with that in pedal skin from healthy controls. CD3+, CD4+, CD8+ and CD21+ cells were commonly observed in perivascular sites in the superficial dermis, periadnexally, beneath the dermal–epidermal (DE) junction and in the epidermis of lesional ImR‐LPP skin. The CD8+/CD3+ T‐cell ratio in peripheral blood was significantly increased in the ImR‐LPP group (0.42 versus 0.35 in controls). Serum IgA, IgG and IgM concentrations were all significantly elevated in affected dogs. Lymphocyte stimulation indices in ImR‐LPP dogs were comparable with control levels except for a lower response to ionomycin (6.0 versus 11.1). Dogs with ImR‐LPP had a higher incidence and mean (semi‐quantitative) score for IgA, IgG and IgM deposits in the epidermis, and a significantly increased incidence of dermal IgA+, IgG+ and IgM+ mononuclear inflammatory cells. The results indicate that upregulated T‐ and B‐lymphocyte responses may contribute to the pathogenesis of the skin lesions observed in dogs with ImR‐LPP.  相似文献   

12.
Dogs have a similar incidence of spontaneous cancers as people, and a noninvasive test to monitor disease status in dogs would be of great value. Humans with cancer often have increased levels of cell‐free circulating DNA in their plasma, which has shown promise for diagnosis, prognosis and detection of residual disease. We hypothesized that dogs with cancer have increased circulating DNA compared with healthy dogs or dogs with non‐neoplastic diseases. Plasma DNA was measured in 40 healthy dogs, 20 dogs with non‐neoplastic diseases and 80 dogs with cancer. The reference interval for plasma DNA in healthy dogs was 1–15 ng mL?1. Dogs with lymphoma and lymphoid leukaemia had significantly higher concentrations (range: 0–91 ng mL?1, P < 0.0001). Antigen receptor rearrangement assays suggest that plasma DNA had the same clonality as the primary lymphoid tumours. Dogs with lymphoid neoplasia and plasma DNA >25 ng mL?1 had shorter remission times than those with < 25 ng mL?1 (P= 0.0116). In contrast to humans, where increased plasma DNA is seen in many diseases, dogs with nonlymphoid malignancies and non‐neoplastic diseases had plasma DNA concentrations similar to healthy dogs. This study shows that a portion of dogs with lymphoid neoplasia have increased tumour‐derived plasma DNA, which serves as a negative prognostic indicator.  相似文献   

13.
In mice and people, administering corticosteroids before chemotherapy can reduce the severity of myelosuppression without reducing antitumour effects. This study investigated whether pretreatment with dexamethasone would reduce the incidence of grade 4 neutropenia in dogs receiving CCNU. Twenty‐five dogs received dexamethasone [0.1 mg kg?1 per os (PO) every 12 h] for 5 days and on the sixth day received CCNU (90 mg m?2 PO). Historical dogs (n = 67) received CCNU alone (90 mg m?2 PO). Forty‐five percent of historical dogs had grade 4 neutropenia, while 64% of dogs pretreated with dexamethasone had grade 4 neutropenia (P = 0.16). Dexamethasone plasma levels were quantified by enzyme‐linked immunosorbent assay in three healthy dogs. Peak plasma concentrations after a single oral 0.1‐mg kg?1 dose were <80 ng mL?1, the minimum level associated with chemoprotective effects of dexamethasone in people. Pretreatment with dexamethasone did not reduce the incidence of grade 4 neutropenia in dogs receiving CCNU.  相似文献   

14.
25‐hydroxyvitamin D (25(OH)D) is important in bone health as well as many diseases including cancer. Supplementation may increase responsiveness of cancer cells to chemotherapy. Serum 25(OH)D, intact parathyroid hormone (iPTH) and canine C‐reactive protein (c‐CRP) were measured in healthy dogs and dogs with haemoabdomen. Regression analysis determined optimal 25(OH)D concentrations. In healthy dogs (n = 282), mean iPTH concentrations correlated inversely (r2 = 0.88, P < 0.001) to 25(OH)D concentrations. Variation in both iPTH and c‐CRP plateaued at 25(OH)D concentrations of 100–120 ng mL?1. Haemoabdomen dogs (n = 63, 43 malignant and 20 benign) had 25(OH)D concentrations ranging from 19.4 to >150 ng mL?1. Relative risk of cancer increased with decreasing 25(OH)D concentrations [RR = 3.9 for 25(OH)D below 40 ng mL?1 (P = 0.0001)]. Serum 25(OH)D concentrations in dogs vary widely, and are influenced by dietary VitD content. Serum vitD measurement can identify dogs for which supplementation may improve health and response to cancer therapy.  相似文献   

15.
Sterile haemorrhagic cystitis (SHC) is a known risk of cyclophosphamide treatment; however, most canine reports are case series. This case–control study examined risk factors for SHC in dogs with lymphoma receiving oral cyclophosphamide. Twenty‐two dogs with SHC and 66 control dogs were identified. On univariate analysis, SHC risk factors included age (P = 0.041), induction protocol (P = 0.021) and cumulative cyclophosphamide dose (P = 0.002). On multivariate analysis, increasing cumulative cyclophosphamide dose was associated with increased risk of SHC and the ‘short’ induction protocol (protocol 1) was associated with decreased risk. Controlling for age and induction protocol, odds of SHC increased by 2.21 per 750 mg m?2 increase in cyclophosphamide dose (P = 0.001). SHC from oral cyclophosphamide is a predominately delayed toxicity resulting from high cumulative doses.  相似文献   

16.
Sterile haemorrhagic cystitis (SHC) is a known risk of cyclophosphamide treatment. Diuresis using furosemide is effective in canines when maximally tolerated dosed cyclophosphamide is administered. This retrospective study aimed to determine whether orally administered furosemide decreased the incidence of SHC. Secondary aims were to identify predisposing factors for SHC. One‐hundred and fifteen dogs treated with metronomic cyclophosphamide were analysed retrospectively. Populations were not randomized. 25 dogs (21.7%) developed SHC. Furosemide administration significantly reduced the likelihood of SHC development (P = 0.010, where SHC was diagnosed in 30.3% of dogs administered cyclophosphamide without furosemide, and 10.2% of dogs administered cyclophosphamide with furosemide). Age, gender, breed, bodyweight, number of cyclophosphamide treatments, piroxicam use and previous or pre‐existing disease were not found to be associated with SHC development. This study demonstrates furosemide is effective in the prevention of SHC and its use may be considered when implementing metronomic cyclophosphamide therapy.  相似文献   

17.
The purpose of this study was to evaluate the short‐term adverse events (AEs) in dogs with mast cell tumours (MCT) receiving prednisone and dose‐escalating vinblastine (VBL). Twenty‐four dogs were treated with intravenous VBL starting at 2 mg m?2 and then escalating in weekly increments to 2.33, 2.67 and 3 mg m?2. AEs were graded using a standardized scoring system. No dogs receiving 2 or 2.33 mg m?2 experienced grade 3 or 4 AEs. Among the dogs, 9.5 and 5.9% had grade 3 or 4 AEs at dosages of 2.67 and 3 mg m?2, respectively. Serious AEs included neutropaenia (n = 3) and vomiting (n = 1), only one of which required hospitalization. These data indicate that VBL chemotherapy may be safe to administer at higher than the traditional 2 mg m?2 dosage for dogs with MCT. Randomized prospective trials are necessary to establish whether dose escalation will translate into improved response rates when compared with the standard 2 mg m?2 dosage.  相似文献   

18.
Regulatory T cells (Tregs) play a critical role in the maintenance of the host's immune system. Tregs, particularly CD4+CD25+Foxp3+ T cells, have been reported to be involved in the immune evasion mechanism of tumors and several pathogens that cause chronic infections. Recent studies showed that a Treg-associated marker, cytotoxic T-lymphocyte antigen 4 (CTLA-4), is closely associated with the progression of several diseases. We recently reported that the proportion of Foxp3+CD4+ cells was positively correlated with the number of lymphocytes, virus titer, and virus load but inversely correlated with IFN-γ expression in cattle infected with bovine leukemia virus (BLV), which causes chronic infection and lymphoma in its host. Here the kinetics of CTLA-4+ cells were analyzed in BLV-infected cattle. CTLA-4 mRNA was predominantly expressed in CD4+ T cells in BLV-infected cattle, and the expression was positively correlated with Foxp3 mRNA expression. To test for differences in the protein expression level of CTLA-4, we measured the proportion of CTLA-4-expressing cells by flow cytometry. In cattle with persistent lymphocytosis (PL), mean fluorescence intensities (MFIs) of CTLA-4 on CD4+ and CD25+ T cells were significantly increased compared with that in control and aleukemic (AL) cattle. The percentage of CTLA-4+ cells in the CD4+ T cell subpopulation was positively correlated with TGF-β mRNA expression, suggesting that CD4+CTLA-4+ T cells have a potentially immunosuppressive function in BLV infection. In the limited number of cattle that were tested, the anti-CTLA-4 antibody enhanced the expression of CD69, IL-2, and IFN-γ mRNA in anti-programmed death ligand 1 (PD-L1) antibody-treated peripheral blood mononuclear cells from BLV-infected cattle. Together with previous findings, the present results indicate that Tregs may be involved in the inhibition of T cell function during BLV infection.  相似文献   

19.
Background: Continuous administration of low doses of cyclophosphamide and standard doses of cyclooxygenase‐inhibiting drugs has been shown to suppress tumor angiogenesis, reverse immunosuppression, and deplete regulatory T cells in cancer models. Hypothesis: We hypothesized that continuous treatment with low‐dose cyclophosphamide and full‐dose piroxicam would delay tumor recurrence in dogs with soft tissue sarcomas (STS). Animals: Eighty‐five dogs with incompletely resected STS, 30 treated dogs, and 55 contemporary control dogs. Methods: Treatment outcomes in 85 dogs with incompletely resected STS were evaluated in a retrospective study. Dogs in the treatment group received continuously administered low‐dose cyclophosphamide (10 mg/m2) and standard dose piroxicam (0.3 mg/kg) therapy. Time to local tumor recurrence (disease‐free interval; DFI) was compared between the 30 treated dogs and 55 untreated control dogs matched for age and tumor site and grade. Results: DFI was significantly (P < .0001) prolonged for STS of all sites (trunk and extremity) in treated dogs compared with untreated control dogs. The DFI also was significantly longer in treated dogs when tumor site (trunk and extremity) was compared. Twelve treated dogs (40%) experienced mild toxicity (grade 1 and 2) at some point during treatment and 1 dog developed grade 4 cystitis. Every other day dosing was tolerated better than daily dosing. Conclusions: Metronomic therapy with cyclophosphamide and piroxicam was very effective in preventing tumor recurrence in dogs with incompletely resected STS. These findings suggest that further evaluation of this approach is warranted as adjuvant therapy in dogs with highly metastatic tumors such as osteosarcoma and melanoma.  相似文献   

20.
Pyometra is a serious problem in dairy cow herds, causing large economic losses due to infertility. The development of pyometra depends mainly on the immunological status of the cow. The aim of the study was a comparative evaluation of selected indicators involving non‐specific and specific immunity in cows with pyometra and in cows without inflammation of the uterus. The study was performed in 20 cows, which were divided into two groups: pyometra group and healthy group, each comprising 10 cows, based on the results of cytological and ultrasonographic tests. A flow cytometric analysis was performed for the surface molecules CD4, CD8, CD14, CD21, CD25 and CD4+CD25+ on leucocytes, and the phagocytic activity was determined from granulocytes and monocytes/macrophages in the peripheral blood and uterine washings, respectively. It was demonstrated that the percentage of phagocytic granulocytes and monocytes/macrophages in both the peripheral blood and uterine washings was significantly lower in cows with pyometra compared with the healthy group (p < 0.001). Significantly (p ≤ 0.001) lower percentage of CD4+, CD14+, CD25+ and CD4+CD25+ phenotype leucocytes was also observed in the peripheral blood of cows from the pyometra group, along with a significantly higher (p < 0.001) percentage of CD8+ and CD21+ lymphocytes as compared to the healthy group. The results of work indicate that disfunction of cell immunity coexisting with pyometra may be caused by a bacterial infection and the presence of blocking agents (IL‐10), released by the increasing number of CD8+ lymphocytes what leads to the advanced inflammation of uterus.  相似文献   

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