Serum neopterin levels in female dogs with malignant mammary tumours

In this study, we have determined serum neopterin levels in female dogs with primary malignant mammary tumours. The study involved 50 female dogs which had a malignant mammary tumours removed surgically (32 animals with carcinoma, 12 animals with sarcoma and 6 animals with carcinosarcoma) and 10 clinically healthy female dogs. Serum neopterin levels were determined using a commercial ELISA kit. The mean neopterin levels were lower in the malignant tumour groups than in healthy animals but differences were statistically significant only in carcinoma and sarcoma groups. The decrease of neopterin levels in animals with malignant mammary tumours may suggest their decreased cellular immunity. Moreover, it might indicate that decreased activity of cellular mechanisms of the anti‐neoplastic response is one of the factors associated with the development and course of malignant mammary tumours in female dogs; however, further studies are necessary.     

PCNA and grade in 13 canine oral squamous cell carcinomas: association with prognosis

This study evaluated the prognosis factors of age, tumour size, anatomic location, histological grade and proliferating cell nuclear antigen (PCNA) expression in 13 dogs with oral squamous cell carcinoma (OSCC) with bone invasion and without signs of lymph node or distant metastasis. All animals were treated with radical excision performed with at least 1 cm margin, based on computed tomography images. In the 2‐year follow‐up, median disease‐free survival was 138 days for dogs with grade 3 tumours and was not reached for those with grade 2 tumours. Grade 3 tumours and PCNA labelling index ≥65% were related with a shorter disease‐free survival time and consequently poor prognosis (p = 0.003 and p = 0.034, respectively). Mean PCNA labelling index was significantly higher in recurrent cases (p = 0.011). Histological grade and PCNA expression may be important prognosis factors in canine OSCC.     

Prognostic impact of neoadjuvant aglepristone treatment in clinicopathological parameters of progesterone receptor‐positive canine mammary carcinomas

Neoadjuvant treatment of canine mammary carcinomas with the progesterone receptor (PR) antagonist aglepristone has a PR expression‐related inhibiting effect on proliferation index (PI). The aim of this study was to evaluate the effect of the treatment in the disease‐free period (DFP) and overall survival (OS) of canine mammary carcinomas. Fifty female dogs with mammary carcinomas were treated with aglepristone (n = 34) or oil vehicle (n = 16) before surgery (day 15). PR expression and PI were analysed by immunohistochemistry in samples taken at days 1 and 15. Epidemiological and clinicopathological data were assessed. DFP and OS data were retrieved every 4–6 months for at least 24 months after surgery. Aglepristone treatment increased DFP of animals bearing PR+ tumours with size smaller than 3 cm, complex and mixed tumours, with histologic grades I and II, and with PI ≤ 10%. Although further studies are necessary, current evidence points to treatment with aglepristone as useful for the management of canine mammary tumours.     

Serum Cytokine Profiling in Cats with Acute Idiopathic Cystitis

Background

Feline idiopathic cystitis (FIC) is a common lower urinary tract disorder of domestic cats that resembles interstitial cystitis/painful bladder syndrome (IC/PBS) in humans. Diagnosis of FIC is based on clinical signs and exclusion of other disorders because of a lack of specific pathologic findings or other objective biomarkers. Cytokines are potential noninvasive biomarkers to define the presence, severity, and progression of disease, and response to treatment.

Objectives

The objective of this pilot study was to determine concentrations of selected cytokines in serum from healthy cats and cats with acute FIC.

Animals

Serum samples from 13 healthy cats and from 12 cats with nonobstructive acute FIC were utilized.

Methods

Multiplex analysis of 19 cytokines (CCL2, CCL5, CXCL1, CXCL12, CXCL8, Flt3L, GM‐CSF, IFN‐γ, IL‐12 (p40), IL‐13, IL‐18, IL‐1β, IL‐2, IL‐4, IL‐6, PDGF‐BB, SCF, sFas, and TNF‐α) was performed with a commercially available feline‐specific multiplex bead‐based assay.

Results

Mean serum concentrations of IL‐12 (p40; P < 0.0001), CXCL12 (P = 0.002), IL‐18 (P = 0.032), and Flt3L (P = 0.0024) were significantly increased in FIC cats compared to healthy cats. GM‐CSF, IL‐1b, IL‐2, and PDGF‐BB were undetectable or detected in an insufficient number of cats to allow meaningful comparisons.

Conclusions and Clinical Importance

We have identified increased serum concentrations of pro‐inflammatory cytokines and chemokines CXCL12, IL‐12, IL‐18, and Flt3L in FIC‐affected cats. These findings suggest potential candidates for noninvasive biomarkers for diagnosis, staging, and therapeutic outcome monitoring of affected cats and provide additional insight into the etiopathogenesis of FIC.     

A retrospective analysis of chemotherapy switch suggests improved outcome in surgically removed,biologically aggressive canine haemangiosarcoma

Haemangiosarcoma (HSA) has an aggressive biological behaviour and carries a poor prognosis, with less than 10% of treated dogs surviving longer than 1 year. In this retrospective study a varied metronomic chemotherapy (MC) regimen preceded by adjuvant doxorubicin‐based maximum‐tolerated dose chemotherapy (MTDC) was compared with MTDC, in terms of efficacy [time to metastasis, (TTM) and survival time (ST)] and safety in dogs with biologically aggressive HSA. Dogs were eligible if they had no metastasis after MTDC and received either no further chemotherapy or MC maintenance. Twelve dogs received MTDC, and 10 received MC thereafter. Median TTM and ST were significantly longer for dogs receiving MTDC‐MC (not reached versus 150 days, P = 0.028; and not reached versus 168 days, P = 0.030, respectively). Treatment was well tolerated. MTDC followed by MC is safe and suggests improved TTM and ST in dogs with surgically removed, biologically aggressive HSA that are treated in the microscopic setting.     

Digital hypothermia inhibits early lamellar inflammatory signalling in the oligofructose laminitis model

Reasons for performing study: The pathophysiological events inhibited by prophylactic digital hypothermia that result in reduction of the severity of acute laminitis are unknown. Objectives: To determine if digital hypothermia inhibits lamellar inflammatory signalling during development of oligofructose (OF) induced laminitis. Methods: Fourteen Standardbred horses were given 10 g/kg bwt OF by nasogastric tube with one forelimb (CRYO) continuously cooled by immersion in ice and water and one forelimb (NON‐RX) at ambient temperature. Lamellae were harvested prior to the onset of lameness (24 h post OF administration, DEV group, n = 7) or at the onset of lameness (OG1 group, n = 7). Lamellar mRNA was purified and cDNA produced for real time‐quantitative PCR analysis of mRNA concentrations of cytokines (IL‐6, IL‐1β, IL‐10), chemokines (CXCL1, CXCL6, CXCL8/IL‐8, MCP‐1, MCP‐2), cell adhesion molecules (ICAM‐1, E‐selectin), COX‐2 and 3 housekeeping genes. Data were analysed (NON‐RX vs. CRYO, NON‐RX vs. archived control [CON, n = 7] lamellar tissue) using nonparametric tests. Results: Compared with CON, the OG1 NON‐RX had increased (P<0.05) lamellar mRNA concentrations of all measured mediators except IL‐10, IL‐1β and MCP‐1/2, whereas only CXCL8 was increased (P<0.05) in DEV NON‐RX. Within the OG1 group, CRYO limbs (compared with NON‐RX) had decreased (P<0.05) mRNA concentrations of the majority of measured inflammatory mediators (no change in MCP‐1 and IL‐10). Within the DEV group, mRNA concentrations of CXCL‐1, ICAM‐1, IL‐1β, CXCL8 and MCP‐2 were decreased (P<0.05) and the anti‐inflammatory cytokine IL‐10 was increased (compared with NON‐RX limbs; P<0.05). Conclusions: Digital hypothermia effectively blocked early lamellar inflammatory events likely to play an important role in lamellar injury including the expression of chemokines, proinflammatory cytokines, COX‐2 and endothelial adhesion molecules. Potential relevance: This study demonstrates a potential mechanism by which hypothermia reduces the severity of acute laminitis, and may help identify molecular targets for future laminitis intervention.     

Ultrasound and computed tomography of the iliosacral lymphatic centre in dogs with anal sac gland carcinoma

In this prospective study, we hypothesized that computed tomography (CT) would identify more normal and abnormal iliosacral lymph nodes (LNs) than abdominal ultrasound in dogs with anal sac gland carcinoma (ASGC). Twelve client‐owned dogs with ASGC but without distant metastasis were enrolled. Abdominal ultrasound and contrast‐enhanced CT scans of the abdomen were obtained. Iliosacral LNs were counted and assessed for location, laterality and size. Significantly (P < 0.00001) more iliosacral LNs were identified with CT (61) than ultrasound (30), including significantly (P = 0.00012) more medial iliac LNs with CT (33) than ultrasound (19). There was no difference in number of internal iliac LNs identified with CT versus ultrasound. Significantly (P = 0.000061) more sacral LNs were identified with CT (15) than ultrasound (0). Ultrasound identified slightly more (7) abnormal iliosacral LNs than CT (5). Contrast CT was able to identify more normal but not more abnormal LNs than ultrasound.     

Canine mammary gland tumours; a histological continuum from benign to malignant; clinical and histopathological evidence*

This study describes the clinical and histopathological findings in dogs with mammary gland tumours, and compares the histopathological and clinical evidence consistent with progression from benign to malignant to human breast cancer epidemiology. Clinical and histopathological data on 90 female dogs with 236 tumours was included. Dogs with malignant tumours were significantly older than dogs with benign tumours (9.5 versus 8.5 years), P = 0.009. Malignant tumours were significantly larger than benign tumours (4.7 versus 2.1 cm), P = 0.0002. Sixty‐six percent had more than one tumour, and evidence of histological progression was noted with increasing tumour size. Dogs with malignant tumours were significantly more likely to develop new primary tumours than dogs with benign tumours, P = 0.015. These findings suggest that canine mammary tumours progress from benign to malignant; malignant tumours may be the end stage of a histological continuum with clinical and histopathological similarities to human breast carcinogenesis.     

Intratumoural interleukin 12 gene therapy stimulates the immune system and decreases angiogenesis in dogs with spontaneous cancer

Interleukin 12 (IL‐12) is a powerful immunostimulatory cytokine with a strong antitumoural activity. In this work, the immunological, anti‐angiogenic and clinical effects of three consecutive intratumoural IL‐12 electrogene therapy (EGT) treatments were evaluated in nine dogs with spontaneous cancer. In all the dogs, tumour biopsies and blood samples were taken prior, during and after the intratumoural IL‐12 EGT (on days 1, 8, 35 and 1, 3, 8, 15, 35, respectively). An initial decrease in immune cells was followed by an increase above baseline 1–3 weeks after treatment initiation. Interestingly, the decrease in peripheral leukocytes 2 days after the first intratumoural IL‐12 EGT coincided with erythema and tumour swelling. Transient increases of IL‐12 and interferon γ were measured in the serum and the tumour tissue, whereas IL‐10 transiently increased only in the serum. The effect of intratumoural IL‐12 EGT on the levels of IL‐24 and vascular endothelial growth factor in the sera and tumour biopsies differed per dog. Via contrast‐enhanced ultrasound (US) (on days 1, 8 and 35), we demonstrated that intratumoural IL‐12 EGT resulted in a significant decrease of the relative blood volume and blood flow speed in the tumour compared with baseline. Metastases were present in two dogs. In one of these dogs, IL‐12 EGT of the primary tumour caused a transient partial regression of the metastases, but not of the primary tumour. The second dog with metastases did not survive long enough to complete the entire treatment cycle. Despite encouraging immunostimulatory and anti‐angiogenic effects after intratumoural IL‐12 EGT, no clinically relevant outcomes were observed in this study, as persistent tumour regression could not be obtained. On the other hand, the laboratory and US results hold great promise for combinatorial strategies of intratumoural IL‐12 EGT with conventional antitumour (immuno)therapies.     

Long‐term survival in dogs with localized histiocytic sarcoma treated with CCNU as an adjuvant to local therapy*

Histiocytic sarcoma (HS) is associated with a poor prognosis owing to the presence of metastasis at the time of diagnosis in most dogs. Improved outcome has been reported in several dogs with localized HS following local therapy, however, distant metastasis occurs in 70–91% of dogs suggesting that adjuvant systemic therapy is necessary. The purpose of this retrospective study was to describe clinical characteristics and outcome in dogs with localized HS treated with aggressive local therapy plus adjuvant CCNU chemotherapy. Data from 16 dogs were evaluated. The median disease‐free interval was 243 days. Two dogs had local recurrence and eight dogs developed metastatic disease with a median time to relapse of 201 days in these 10 dogs. The median survival time for all 16 dogs was 568 days. These results support the recommendation for aggressive local therapy combined with adjuvant CCNU chemotherapy in dogs with localized HS.     

Cytologic examination of fine‐needle aspirates from mammary gland tumors in the dog: diagnostic accuracy with comparison to histopathology and association with postoperative outcome

Background: Mammary tumors are the most common neoplasms in female dogs. Malignant tumors may carry a poor prognosis and necessitate surgery. Few data are available on the value of cytologic examination as a diagnostic or prognostic tool for mammary tumors in dogs. Objectives: The objectives of this study were to determine whether cytologic findings in fine‐needle aspirate specimens of canine mammary tumors correlate with histopathologic results and whether the cytologic diagnosis is associated with postoperative outcome. Methods: In this prospective study, fine‐needle aspirate samples were obtained from 50 mammary tumors in 50 dogs. Results of cytologic and histopathologic examination were compared, using the histologic diagnosis as the reference method. Kaplan–Meier log rank analysis was used to evaluate univariate association of the cytologic diagnosis with duration of survival, local control, and metastasis‐free interval. Results: Adequate cytologic samples were obtained in 43/50 (86%) cases. The cytologic diagnosis correlated with the histologic diagnosis for benign and malignant tumors in 40/43 (93%) and 35/43 (81%) cases, respectively. Cytologic examination had a sensitivity of 88% and a specificity of 96% for the diagnosis of malignancy. The cytologic diagnosis had significant univariate association with duration of survival (P=.016), recurrence‐free interval (P=.003), and metastasis‐free interval (P=.014). Conclusions: Cytologic examination of mammary tumors in the dog has satisfactory accuracy, sensitivity, and specificity for the diagnosis of malignancy and is associated with postoperative outcome. Further studies on the diagnostic accuracy of cytology as well as multivariate analysis of its preoperative prognostic value in mammary tumors in the dog are warranted.     

Fermented Maesil (Prunus mume) with probiotics inhibits development of atopic dermatitis‐like skin lesions in NC/Nga mice

Maesil (Prunus mume Siebold & Zucc.), a potential source of free radical scavengers and inhibitor of pro‐inflammatory mediators, is used in traditional Korean medical preparations as a remedy for skin disorders as have probiotics. The action of a probiotic fermented Maesil preparation on the development of atopic dermatitis (AD)‐like skin lesions was determined in a NC/Nga mouse model as an initial step towards the development of a therapeutic feed supplement for use in dogs. Continuous ingestion of the experimental feed markedly inhibited the development of the AD‐like skin lesions, as evidenced by a marked decrease in skin signs and reduced inflammation within the skin lesions. Efficacy was confirmed by significant decreases in eosinophil ratio and serum IgE concentration, and a reduction in the number of Staphylococcus aureus recovered from the ear. Relative mRNA expression levels of IL‐4, interferon‐γ and tumour necrosis factor‐α in the spleens of the experimental animals were also decreased and there was an increased serum concentration of IL‐10 with a concurrent decreased IL‐4 concentration in comparison to a control group. Taken together, the results indicate that some component(s) of fermented Maesil have the ability to suppress the development of AD‐like skin lesions, possibly by stimulation of IL‐10. Beneficial effects of fermented Maesil may thus be expected in dogs with AD, although this and the nature of the active pathway remain to be explored.     

High‐mobility group box 1 as a surrogate prognostic marker in dogs with systemic inflammatory response syndrome

Objective – To evaluate various surrogate markers associated with the inflammatory and counter‐inflammatory responses with respect to mortality in dogs with systemic inflammatory response syndrome (SIRS). Design – Prospective observational study. Setting – Veterinary Teaching Hospital. Animals – Twenty‐eight dogs with naturally occurring diseases and SIRS from January 2007 to May 2009. Interventions – Upon admission to the veterinary hospital, history and baseline data from the physical examination, including parameters previously defined for meeting SIRS criteria, were documented. Heparinized blood samples were collected and plasma cytokines interleukin‐6 (IL‐6), IL‐10, and high‐mobility group box 1 (HMGB1) were measured by sandwich ELISA. Measurements and Main Results – In nonsurvivors, median plasma HMGB1 concentrations (0.718 μg/L, interquartile range [IQR]; 0.300–1.626 μg/L) and the ratio of HMGB1 to IL‐10 (2.236, IQR; 0.972–5.367) were significantly increased as compared with those found in survivors (0.300 μg/L, IQR; 0.300–0.312 μg/L for HMGB1; 1.017, IQR; 0.862–1.126 for the ratio of HMGB1 to IL‐10, P=0.007 and 0.024, respectively). Plasma IL‐6, IL‐10, and the ratio of IL‐6 to IL‐10 were not significantly different between groups. Among the parameters studied, HMGB1 and the ratio of HMGB1 to IL‐10 performed the best in discriminating outcome in dogs with SIRS according to receiver operator characteristic curve analysis. Conclusions – Increases in plasma HMGB1 concentration and the ratio of HMGB1 to IL‐10 may predict poorer outcomes in dogs with SIRS. The approach described may lead to reliable prognostic biomarkers and new therapeutic concepts in the study of SIRS in dogs.     

Efficacy of doxorubicin‐based chemotherapy for non‐resectable canine subcutaneous haemangiosarcoma

Eighteen dogs with measurable subcutaneous haemangiosarcoma (SQHSA) were treated with doxorubicin‐based chemotherapy. Response assessment was evaluated and compared using World Health Organization (WHO), Response Evaluation Criteria in Solid Tumours (RECIST) and tumour volume criteria. The overall response rate for all dogs was 38.8% using WHO criteria, 38.8% using RECIST criteria and 44% using tumour volume criteria. One dog had a complete response. The median response duration for all dogs was 53 days (range 13–190 days). Four dogs had complete surgical excision after neoadjuvant chemotherapy. The median progression‐free interval for dogs with complete surgical excision after neoadjuvant chemotherapy was significantly longer than those not having surgical excision (207 days versus 83 days, respectively) (P = 0.003). No significant difference in metastasis‐free interval or survival time was found between the groups. Doxorubicin‐based chemotherapy appears to be effective for non‐resectable canine SQHSA, although the response duration is relatively short.     

Outcome following treatment of soft tissue and visceral extraskeletal osteosarcoma in 33 dogs: 2008–2013

Extraskeletal osteosarcoma (EOS) is a rare, highly malignant mesenchymal neoplasm arising from viscera or soft tissues characterised by the formation of osteoid in the absence of bone involvement. Owing to the rarity of these neoplasms very little information exists on treatment outcomes. The purpose of this study was to describe the outcome following surgical treatment of non‐mammary and non‐thyroidal soft tissue and visceral EOS in dogs. Thirty‐three dogs were identified; the most common primary tumour site was the spleen. Dogs that had wide or radical tumour excision had longer survival times compared with dogs that had only marginal tumour excision performed [median survival time of 90 days (range: 0–458 days) versus median survival time of 13 days (range: 0–20 days)]. The use of surgery should be considered in the management of dogs with non‐mammary and non‐thyroidal soft tissue and visceral EOS.     

Adjuvant anthracycline‐based vs metronomic chemotherapy vs no medical treatment for dogs with metastatic splenic hemangiosarcoma: A multi‐institutional retrospective study of the Italian Society of Veterinary Oncology

Treatment options for dogs with metastatic (stage III) splenic hemangiosarcoma are limited. A doxorubicin‐based chemotherapy regimen is commonly administered; however, there are no published data to support this practice. The aim of this study was to investigate the impact of maximum‐tolerated‐dose chemotherapy (MTD), metronomic chemotherapy (MC) and no adjuvant treatment on outcome in dogs with stage III splenic hemangiosarcoma undergoing splenectomy. Medical records of dogs with stage III splenic hemangiosarcoma that underwent splenectomy followed by MTD chemotherapy, MC or no adjuvant treatment were retrieved. Time to progression (TTP), survival time (ST) and toxicity were evaluated. One hundred three dogs were identified: 23 received adjuvant MTD, 38 MC and 42 were not medically treated. Overall median TTP and ST were 50 (95% confidence interval [CI], 39‐61) and 55 days (95% CI, 43‐66), respectively. Dogs treated with adjuvant MTD had a significantly longer TTP and ST compared with dogs receiving MC (median TTP, 134 vs 52 days, P = .025; median ST, 140 vs 58 days, P = .023, respectively). Dogs treated by splenectomy only had the shortest median TTP (28 days) and ST (40 days). However, treatment‐related adverse events (AEs) were significantly more frequent in the MTD group (P = .017). The outcome for dogs with metastatic splenic hemangiosarcoma is poor. While MTD showed greater efficacy compared to MC, toxicity was higher in this group. Treatment‐related AEs need to be carefully balanced against this modest survival prolongation when offering adjuvant MTD to dogs with advanced stage hemangiosarcoma.     

Incorporation of sentinel lymph node mapping in dogs with mast cell tumours: 20 consecutive procedures

The study hypothesis is that incorporation of sentinel lymph node (SLN) mapping in dogs presenting for mast cell tumour (MCT) removal would impact the recommended adjuvant therapy offered. Nineteen dogs were enrolled having either spontaneously occurring or incompletely excised MCTs. Staging included regional lymph node aspiration. SLN mapping was done with regional lymphoscintigraphy combined with intra‐operative lymphoscintigraphy and blue dye. Twenty MCTs in 19 dogs were excised with SLN mapping. Eight dogs had SLNs different from the closest node. Twelve dogs had metastasis in extirpated SLNs, seven occurred in MCTs with a MI ≤ 5. No correlation was noted between patient stage and the c‐KIT proto‐oncogene. Because of SLN staging, 8 of 19 dogs were offered additional therapy that would have otherwise been excluded. Anatomic sampling of lymph nodes in dogs with MCTs does not accurately reflect which lymph nodes are most likely to be receiving the draining tumour lymph.     

Outcome in dogs with advanced (stage 3b) anal sac gland carcinoma treated with surgery or hypofractionated radiation therapy

Stage 3b anal sac gland carcinoma (ASGC) can be life‐threatening. A surgical approach is not always possible or may be declined. Dogs with stage 3b ASGC treated with surgery or conformal radiation therapy (RT) with 8 × 3.8 Gy (total dose 30.4 Gy, over 2.5 weeks) were retrospectively evaluated. Patient characteristics, median progression‐free interval (PFI) and median survival time (MST) were compared. Twenty‐eight dogs were included; 15 underwent surgery, 13 underwent RT. At the time of presentation, 21% showed life‐threatening obstipation and 25% showed hypercalcaemia. PFI and MST for surgery cases were 159 days (95% CI: 135–184 days) and 182 days (95% CI: 146–218 days), both significantly lower than for RT cases with 347 days (95% CI: 240–454 days) and 447 days (95% CI: 222–672 days), (P = 0.01, P = 0.019). Surgery as well as RT led to a fast relief of symptoms. PFI and survival of surgical patients were significantly inferior to that of a comparable patient group treated with conformal hypofractionated RT.     

Postoperative adjuvant treatment of invasive malignant mammary gland tumors in dogs with doxorubicin and docetaxel

BACKGROUND: Treatment outcome after surgery alone is unsatisfactory in dogs with invasive malignant mammary gland tumors. HYPOTHESIS: Adjuvant doxorubicin or docetaxel will improve the treatment outcome in dogs with high-risk malignant mammary gland tumors, and the use of docetaxel will be feasible in affected dogs. ANIMALS: Thirty-one dogs with malignant mammary gland tumors of histologic stages II and III (vascular or lymphatic invasion, regional lymph node metastasis, or distant metastasis) were used. METHODS: A prospective clinical trial in which dogs were treated with surgery alone (n = 19) or also received adjuvant chemotherapy (n = 12) with doxorubicin or docetaxel was conducted. Docetaxel was given as an IV infusion at a dose of 30 mg/m2 preceded by dexamethasone and diphenhydramine administration. RESULTS: The recurrence-free interval ranged from 13 to 2,585 days (median not reached); the median metastasis-free interval and overall survival were 294 days and 370 days, respectively. Dogs treated with chemotherapy had a tendency toward higher long-term local control and survival rates, but there was no significant difference in the recurrence-free interval (P = .17), time to metastasis (P = .71), and overall survival (P = .12). Factors found to influence the time to metastasis and overall survival included lymph node metastasis (P = .009) and tumor fixation to underlying structures (P = .043, time to metastasis), as well as age (P = .018) and histologic stage (P < .001, survival). Mild allergic skin reactions were the most frequently observed complications of docetaxel treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Chemotherapy did not lead to an improved outcome in this population. Docetaxel treatment was well tolerated. Additional investigations of adjuvant chemotherapy in dogs with high-risk mammary cancer are warranted.     

Interleukin-8 as a prognostic serum marker in canine mammary gland neoplasias

Mammary gland tumors in female dogs are an excellent model for the clinic-pathological, diagnostic and prognostic investigation of mammary neoplasias. Prognostic and predictive markers are effective in research and routine diagnosis. Interleukins play a fundamental role in cancer, with a particular function in tumor growth, invasion and metastatic potential. Interleukin-8 (IL-8) is known to possess tumorigenic and pro-angiogenic properties, and its overexpression is seen in a number of human tumors. IL-8 serum levels were determined and correlated with the clinic-pathological features and clinical evolution of mammary gland neoplasias in female dogs. IL-8 was measured by an immunoenzymatic assay in 30 female dogs with mammary neoplasias within a 12 month follow-up and in 50 control animals. The correlation between IL-8 concentration and clinical parameters was investigated. A statistically significant difference in the IL-8 serum levels was found in tumor-bearing dogs compared to the controls. In addition, when the individual parameters were evaluated, IL-8 content showed a positive correlation with the tumor progression, lymph node involvement, recurrence and death. Single and multivariate analyses showed associations between tumor recurrence, metastasis, high clinical staging and high IL-8, and also with the death risk. This was also consistent with the high IL-8 content in dogs showing tumor recurrence and metastasis. IL-8 superexpression has been detected in a number of human tumors, usually associated with a poor prognostic. Besides promoting angiogenesis, IL-8 is strongly related with the metastatic phenotype of mammary tumor cells. High IL-8 concentration was found in mammary gland cancer patients with advanced disease stages. Our results show that IL-8 can be used as a non-invasive prognostic marker for mammary gland cancer, and can be useful for the prediction of disease progression and recurrence in dogs with mammary neoplasias. The increased level of this cytokine acts as an independent prognostic marker of survival and the identification of animals with the poor prognostic.