Influence of Pretreatment Polarographically Measured Oxygenation Levels in Spontaneous Canine Tumors Treated with Radiation Therapy

Background and Purpose:: The level of hypoxia in primary tumors has been described to influence response to treatment. The aim of the present study was to investigate the impact of pretreatment oxygen level measurements in spontaneous canine tumors on treatment outcome. Materials and Methods:: Data of pretreatment tumor oxygenation status and local tumor response after primary radiation therapy in a group of spontaneously occurring tumors in dogs (n = 52) was collected. Radiation therapy was given with curative (14-17 × 3-3.5 Gy) or palliative intent (3 × 8 Gy or 4-5 × 6 Gy). Progression-free interval and overall survival were correlated to polarographically measured tumor oxygenation status. Results:: In the curatively irradiated group, tumors with median pO2 values ≤ 10 mmHg tended to have shorter median progression- free interval compared to better oxygenated tumors (246 vs. 739 days). The same trend could be shown for overall survival (330 vs. 745 days), indicating a cutoff value in this region. In the group treated with lower doses of radiation, the level of oxygen was no longer found to be of prognostic value; however, in this group hemoglobin had a significant impact on outcome. Conclusion:: In curatively irradiated spontaneous canine tumors, tumor hypoxia was found to be a prognostic indicator, independent of tumor histologies and volum

Unterrichtsnachbesprechungen im Rahmen von Schulpraktischen. Studien zwischen Gestaltung von Reflexions- und Lernanlässen und (Selbst-)Bestätigung der Berufswahl. Empirische Analysen zum Adressierungsgeschehen am Studienbeginn

Unterrichtsnachbesprechungen im Rahmen von schulischen Praxisphasen in der Studieneingangsphase stellen besondere Formate der Professionalisierung angehender Lehrkräfte dar, in denen Studierende mit Akteur:innen aus Schule und Hochschule zusammentreffen und sich ein komplexes Adressierungsgeschehen entfaltet. Im Rahmen des Beitrags werden ausgehend von drei empirischen Fällen Adressierungsweisen rekonstruiert, die darauf hinweisen, dass Studierende insbesondere von Seiten der schulischen Praxis in der Studieneingangsphase zu Quasi-Kolleg:innen ‚gemacht‘ werden und dadurch ihre Entwicklungsbedürftigkeit sowie die Notwendigkeit der weiteren wissenschaftlichen (Aus-)Bildung ‚verkannt‘ werden. Diskutiert werden daran anschließend Ambivalenzen im Adressierungsgeschehen und der prekäre Stellenwert der Professionalisierung. (DIPF/Orig.

The influence of fractionated radiation therapy on plasma vascular endothelial growth factor (VEGF) concentration in dogs with spontaneous tumors and its impact on outcome

BACK GROUND AND PURPOSE: Vascular endothelial growth factor (VEGF), a specific pro-angiogenic factor is proposed to be involved in cancer progression and resistance to radiation therapy by promoting angiogenesis and by protecting endothelial cells from radiation induced apoptosis. The aim of this study, was first to assess the influence of ionizing radiation on plasma VEGF concentration in spontaneous canine tumors during fractionated radiation therapy with curative or palliative intent and second to analyze plasma VEGF concentration as predictor for treatment outcome. PATIENTS AND METHODS: For plasma VEGF analysis a human VEGF enzyme linked immunosorbent assay was used. Sixty dogs with various tumor types were included in this study. Dogs were irradiated with either low dose per fx (3-3.5 Gy per fraction, total dose: 42-49 Gy, group A: curative intent) or high dose per fx (6-8 Gy per fraction, total dose: 24-30 Gy, group B: palliative intent). Blood samples were taken before and after dose application at certain time points during therapy. Follow-up evaluation was performed for analysis of time to treatment failure and survival. RESULTS: Repeated measures analysis showed no increase of plasma VEGF in dogs treated with fractionated radiation therapy (group A and B). Dichotomizing baseline plasma VEGF into two groups with high and low plasma VEGF, resulted in shorter time to treatment failure in dogs with high plasma VEGF levels (TTF, group A: P=0.038, group B: P=0.041). CONCLUSIONS: This study demonstrated that dogs with a plasma VEGF level higher than 5 pg/ml had a poorer outcome after radiation therapy. It is therefore, suggested, to use plasma VEGF as predictor for treatment outcome in radiation therapy

Correlation of quantified contrast-enhanced power Doppler ultrasonography with immunofluorescent analysis of microvessel density in spontaneous canine tumours

Conventionally, tumour vascularity is assessed invasively by immunofluorescent analysis. Quantified contrast-enhanced power Doppler ultrasound has been used to measure tumour angiogenesis non-invasively in humans and experimental animals. The purpose of this study was to correlate quantified contrast-enhanced power Doppler ultrasound with immunofluorescent results in 45 spontaneous canine tumours. With power Doppler, mean vascularity was high in squamous cell carcinomas, moderate in malignant oral melanomas and low in sarcomas. There was high mean vascularity in squamous cell carcinomas and low mean vascularity in sarcomas and malignant oral melanomas. Although Doppler parameters correlated moderately with microvascular density for all tumours (P=0.004, r=0.4), they did not correlate within histology groups. These analyses show that vascularity differs among canine tumour histology groups. However, dependent on the method used, measurement of tumour vascularity can provide different biological information

Influence of pretreatment polarographically measured oxygenation levels in spontaneous canine tumors treated with radiation therapy

BACKGROUND AND PURPOSE: The level of hypoxia in primary tumors has been described to influence response to treatment. The aim of the present study was to investigate the impact of pretreatment oxygen level measurements in spontaneous canine tumors on treatment outcome. MATERIALS AND METHODS: Data of pretreatment tumor oxygenation status and local tumor response after primary radiation therapy in a group of spontaneously occurring tumors in dogs (n=52) was collected. Radiation therapy was given with curative (14-17x3-3.5 Gy) or palliative intent (3x8 Gy or 4-5x6 Gy). Progression-free interval and overall survival were correlated to polarographically measured tumor oxygenation status. RESULTS: In the curatively irradiated group, tumors with median pO2 values<or=10 mmHg tended to have shorter median progression- free interval compared to better oxygenated tumors (246 vs. 739 days). The same trend could be shown for overall survival (330 vs. 745 days), indicating a cutoff value in this region. In the group treated with lower doses of radiation, the level of oxygen was no longer found to be of prognostic value; however, in this group hemoglobin had a significant impact on outcome. CONCLUSION: In curatively irradiated spontaneous canine tumors, tumor hypoxia was found to be a prognostic indicator, independent of tumor histologies and volume

Plain language summary of publication: Neurexan reduced blood stress biomarkers in sled dogs after exercise

This is a plain language summary of a published peer-reviewed article in English, German, Spanish and Russian. It refers to a veterinary study investigating impact of training-induced stress response in sled dogs during high intensity training. This summary was not peer-reviewed but it represents the opinions of the authors. For a full list of declarations, including funding and author disclosure statements, please read the full open-access article online.</p

7Hsp70 serum levels in pet dogs - a potential diagnostic biomarker for spontaneous round cell tumors

The concentration of circulating heat shock protein 70 (Hsp70) was measured in liquid biopsies of canine tumor patients as a potential biomarker. Compared with rodent tumor models, spontaneously occurring tumors in pet dogs reflect the clinical situation of human patients better, as dogs cohabitate with their owners in the same environment, reach a much older age than rodents, can provide blood samples much more frequently, and receive up-to-date medical care and, similar to humans, their tumors show a high genetic heterogeneity. Due to the species-specific sequence homology of human and canine Hsp70, two human enzyme-linked immunosorbent assay (ELISA) systems (R&D and lipHsp70) were used to measure canine Hsp70 concentrations in serum and plasma. In general, higher Hsp70 concentrations were found in serum compared with plasma samples of dogs, and the lipHsp70 ELISA detected higher peak concentrations of Hsp70 in a broader range than the R&D ELISA. Compared with a tumor-free control group, serum Hsp70 concentrations were higher in tumor-bearing dogs, irrespective of breed, age, body weight, and gender. A sub-classification of the different tumors according to their cytological characteristics revealed significantly elevated Hsp70 serum concentrations in dogs with round cell tumors (p < 0.01), a heterogeneous group of malignancies with hematopoietic origin such as mast cells, plasma cells, lymphocytes, histiocytes, and melanomas. Future studies with larger patient cohorts and well-defined tumor sizes are necessary to elucidate the role of serum Hsp70 as a biomarker for tumor detection and monitoring of outcome in pet animals

Simultaneous application of the vascular endothelial growth factor (VEGF) receptor inhibitor PTK787/ZK 222584 and ionizing radiation does not further reduce the growth of canine oral melanoma xenografts in nude mice

PTK787/ZK 222584 is an inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinases. In this study, the effectiveness of PTK787/ZK 222584 and radiation on canine oral melanoma xenografts was assessed. Xenografts were treated with radiotherapy (4 · 6 Gy), or with PTK787/ZK 222584, or with a combination of both. Treatment efficacy was assessed using a tumour growth delay assay, serial power Doppler and pO2 measurements during and after therapy. There was a significant growth delay for the group treated with radiation alone and for the combined treatment group. However, tumour growth delay was similar in both groups. Tumours were hypoxic before irradiation and no significant re-oxygenation occurred during therapy. In all tumours, vascularity and perfusion were significantly lower at the end of the study but no significant differences in perfusion, vascularity and oxygenation status were observed between and within treatment groups. The combination of PTK787/ZK 222584 and radiotherapy did not perform better than radiotherapy alone in this model

Interrelation of directly measured oxygenation levels, erythropoietin and erythropoietin receptor expression in spontaneous canine tumours

The expression of the hypoxia-inducible protein erythropoietin in tumour cells correlates with levels of tumour hypoxia. Our aim was to look for an interrelation of directly measured oxygenation levels, the presence of tissue erythropoietin and its receptor. Data of tumour oxygenation status, plasma and tissue erythropoietin and its receptor in a group of spontaneously occurring tumours in 15 dogs were collected. Polarographic tumour oxygen partial pressure measurements were obtained and data were correlated. Significant positive correlations were found between tissue erythropoietin and the percentages of pO2 values 610 mmHg. Multivariate analysis revealed no parameters influencing plasma erythropoietin levels. Our results show that a co-expression of erythropoietin receptor and its ligand in spontaneous canine tumours exists, that the level of hypoxia in tumour cells correlates with the level of tissue erythropoietin and suggest the need to be quantitatively and functionally tested as novel prognostic biological parameters in neoplastic tissues

Ultrasound guided, pre-radiation oxygen measurements using polarographic oxygen needle electrodes in spontaneous canine soft tissue sarcomas

BACKGROUND Poor tumour oxygenation is associated with radiation resistance. The recording of pre-treatment oxygenation status has been shown to be of prognostic relevance. MATERIAL AND METHODS Eleven dogs with spontaneously arising soft tissue sarcomas were included in this study. Oxygen partial pressure measurements (pO2) were performed with the Eppendorf method. RESULTS The mean of median pO2 was 9.6 mmHg (range: 0.1-30 mmHg). Four of the nine dogs included in the statistical analysis showed a median pO2 < or = 2.5 mmHg. The natural logarithm of the hypoxic subvolume correlated with the hypoxic fraction < or = 2.5 mmHg (p = 0.0712) and < or 5 mmHg (p = 0.0988). Mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) correlated significantly to several oxygen parameters. CONCLUSION Hypoxia exists in spontaneous canine soft tissue sarcomas and the dog can be used as a reliable model for repeated oxygenation measurements. Ultrasonography assures reliability of needle placement