Functional Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Delivered by Canine Histiocytic Sarcoma Cells Persistently Infected with Engineered Attenuated Canine Distemper Virus.

The immune response plays a key role in the treatment of malignant tumors. One important molecule promoting humoral and cellular immunity is granulocyte-macrophage colony-stimulating factor (GM-CSF). Numerous successful trials have led to the approval of this immune-stimulating molecule for cancer therapy. However, besides immune stimulation, GM-CSF may also accelerate tumor cell proliferation, rendering this molecule a double-edged sword in cancer treatment. Therefore, detailed knowledge about the in vitro function of GM-CSF produced by infected tumor cells is urgently needed prior to investigations in an in vivo model. The aim of the present study was to functionally characterize a persistent infection of canine histiocytic sarcoma cells (DH82 cells) with the canine distemper virus strain Onderstepoort genetically engineered to express canine GM-CSF (CDV-Ondneon-GM-CSF). The investigations aimed (1) to prove the overall functionality of the virally induced production of GM-CSF and (2) to determine the effect of GM-CSF on the proliferation and motility of canine HS cells. Infected cells consistently produced high amounts of active, pH-stable GM-CSF, as demonstrated by increased proliferation of HeLa cells. By contrast, DH82 cells lacked increased proliferation and motility. The significantly increased secretion of GM-CSF by persistently CDV-Ondneon-GM-CSF-infected DH82 cells, the pH stability of this protein, and the lack of detrimental effects on DH82 cells renders this virus strain an interesting candidate for future studies aiming to enhance the oncolytic properties of CDV for the treatment of canine histiocytic sarcomas.

Hypertensive nonobstructive hydrocephalus as main magnetic resonance imaging feature in a dog with disseminated choroid plexus carcinomatosis.

Obstructive or nonobstructive hypertensive hydrocephalus is reported in choroid plexus tumors. Choroid plexus tumors typically present as T2-weighted hyperintense intraventricular masses with occasional cerebrospinal fluid-drop metastasis. Acquired neoplastic nonobstructive hydrocephalus without visible mass lesion in magnetic resonance imaging is not reported in dogs. A 4.5-year-old Rhodesian Ridgeback presented with reduced mental status, unilaterally absent pupillary light reflex, and neck pain. Magnetic resonance imaging revealed a nonobstructive hydrocephalus and widened lumbar subarachnoid space with no evidence of a primary mass lesion. Postmortem examination confirmed a disseminated choroid plexus tumor affecting the ependyma and choroid plexi of all ventricles and the cerebral and lumbar subarachnoid space. Disseminated choroid plexus carcinomatosis should be considered as a possible cause of hypertensive hydrocephalus even in absence of a primary mass.

Erythrocyte sedimentation rate, C-reactive protein, and interleukin-6 as inflammatory biomarkers in dogs naturally infected with Ehrlichia canis.

BACKGROUND AND AIM: Canine monocytotropic ehrlichiosis (CME), a tick-borne disease, leads to a systemic inflammatory response syndrome; it is thus important to assess the intensity of inflammation in order to treat it appropriately. The current study was designed to evaluate hematological, biochemical, and inflammatory parameters in dogs naturally infected with Ehrlichia canis compared with those in healthy dogs. We also assessed the relationship among several inflammation-related parameters and considered these parameters for use as inflammatory biomarkers of CME. MATERIALS AND METHODS: Twenty-eight dogs were divided into two groups based on the results of nested polymerase chain reaction for detecting E. canis, comprising a healthy group (n=11) and an infected group (n=17). A blood sample was collected from each dog to evaluate hematological, biochemical, and inflammatory parameters, with the obtained results being statistically compared between the groups. Moreover, the correlations of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) were investigated in the 28 dogs. RESULTS: In the infected group, the mean levels of red blood cells, hemoglobin, and hematocrit were significantly lower than in the healthy group, while the mean lymphocyte and monocyte counts were higher. The mean levels of ESR and CRP were significantly higher (p<0.05) in the infected group, whereas no significant differences were found in IL-6 levels between the two groups. In the correlation analysis, ESR and CRP levels were highly correlated (p<0.01, r=0.531). CONCLUSION: Elevated ESR and CRP levels were found in dogs naturally infected with E. canis, which also presented mild to moderate inflammation in this study. Moreover, CRP was significantly correlated with ESR, so ESR and CRP may serve as inflammatory biomarkers for monitoring CME.