Postoperative adjuvante Therapie mit einem Mistelextrakt (Viscum album ssp. album) bei Hündinnen mit Mammatumoren

Canine Mammatumoren (CMT) sind wegen ihrer Häufigkeit und hohen Malignitätsrate eine Herausforderung für die Veterinärmedizin. Bisher ist noch keine postoperative adjuvante Therapie als wirksamer Standard etabliert und in den nächsten Jahren wohl auch nicht zu erwarten. Zusätzlich ist die Frage nach der Verträglichkeit einer adjuvanten Therapie mit Erhaltung oder Verbesserung der Lebensqualität (LQ) wichtig. Die Therapie mit Mistelextrakten (Viscum album L.; VAE) ist in der Humanonkologie nach adjuvanter Tumorbasistherapie (Chemotherapie und Bestrahlung) eine sehr häufig verwendete, zusätzliche adjuvante Behandlungsmethode. Auch bei verschiedenen Tierarten werden inzwischen Mistelpräparate in der Onkologie erfolgreich angewendet. Methoden: Überprüfung von Wirkung und Nutzen einer postoperativen, adjuvanten Misteltherapie beim CMT sowie Erfassung der LQ unter der VAE-Behandlung. Ausgewertet wurden 56 Hündinnen mit Mammaadenokarzinom, 33 ausschließlich operierte Kontrolltiere und 23 operierte Tiere, die adjuvant VAE erhielten. Ergebnisse: Die mediane Überlebenszeit (MST) aller Tiere (n= 56) betrug 32 Monate (Interquartilbereich 13–51 Monate). Im deskriptiven Vergleich der Überlebenszeiten (ST) nach Kaplan-Meier waren nach 12, 24, 36 bzw. 48 Monaten noch 24, 20, 15 bzw. 5 Hündinnen (entsprechend 72,7%, 60,6%, 45,1%, 12,4%) der Kontrollgruppe sowie 19, 14, 11 und 1 Hündin (82,6%, 60,9%, 47,8%, 4,3%) der VAE-Gruppe am Leben. Die VAE-Therapie führte zu einem geringeren Gesamtversterberisiko, das statistisch nicht signifikant war (Hazard Ratio (HR) 0,530, 95%-Konfidenzintervall (KI) 0,222–1,262; p = 0,15). Tendenziell (p = 0,07) zeigte sich eine Verringerung des tumorbedingten Sterberisikos auf 25% (HR 0,251, 95%-KI 0,056–1,122). Schlussfolgerungen: Es kann eine Tendenz zur Senkung des tumorbedingten Sterberisikos der VAEGruppe bei guter Verträglichkeit der Therapie angenommen werden. Die LQ der Tiere blieb über die gesamte Beobachtungszeit auf hohem Niveau stabil

A three-dimensional ex vivo tri-culture model mimics cell-cell interactions between acute myeloid leukemia and the vascular niche

Ex vivo studies of human disease, such as acute myeloid leukemia, are generally limited to the analysis of two-dimensional cultures which often misinterpret the effectiveness of chemotherapeutics and other treatments. Here we show that matrix metalloproteinase-sensitive hydrogels prepared from poly(ethylene glycol) and heparin functionalized with adhesion ligands and pro-angiogenic factors can be instrumental to produce robust three-dimensional culture models, allowing for the analysis of acute myeloid leukemia development and response to treatment. We evaluated the growth of four leukemia cell lines, KG1a, MOLM13, MV4-11 and OCI-AML3, as well as samples from patients with acute myeloid leukemia. Furthermore, endothelial cells and mesenchymal stromal cells were co-seeded to mimic the vascular niche for acute myeloid leukemia cells. Greater drug resistance to daunorubicin and cytarabine was demonstrated in three-dimensional cultures and in vascular co-cultures when compared with two-dimensional suspension cultures, opening the way for drug combination studies. Application of the C-X-C chemokine receptor type 4 (CXCR4) inhibitor, AMD3100, induced mobilization of the acute myeloid leukemia cells from the vascular networks. These findings indicate that the three-dimensional tri-culture model provides a specialized platform for the investigation of cell-cell interactions, addressing a key challenge of current testing models. This ex vivo system allows for personalized analysis of the responses of patients’ cells, providing new insights into the development of acute myeloid leukemia and therapies for this disease

Alumni Voices

Session was facilitated by Dr. Lawrence Burnley and moderated by Dr. Daria Graham ’92 ’01 ’18, associate vice president for student affairs and dean of students at California State University, San Bernardino. Panelists included Angela Heath ’78 ’80; Darius Beckham ’19; Lisa Rich-Milan ’85; and Dr. Marcus Smith ’08 ’10. These proceedings are available free for download but also available for purchase in print for $6 plus tax and shipping.https://ecommons.udayton.edu/global_voices_4/1009/thumbnail.jp

ArthroRad trial: multicentric prospective and randomized single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis depending on the dose-results after 3 months' follow-up

Purpose Randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regime Patients and methods Patients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice weekly; experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used. Results A total of 64 knees and 172 hands were randomized. 3.0 Gy was applied to 87 hands and 34 knees, 0.3 Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3 Gy and after 0.3 Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment. Conclusion We found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3 Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders

Induction of tolerogenic lung CD4+ T cells by local treatment with a pSTAT-3 and pSTAT-5 inhibitor ameliorated experimental allergic asthma

Signal transducer and activator of transcription (STAT)-3 inhibitors play an important role in regulating immune responses. Galiellalactone (GL) is a fungal secondary metabolite known to interfere with the binding of phosphorylated signal transducer and activator of transcription (pSTAT)-3 as well of pSTAT-6 dimers to their target DNA in vitro. Intra nasal delivery of 50 μg GL into the lung of naive Balb/c mice induced FoxP3 expression locally and IL-10 production and IL-12p40 in RNA expression in the airways in vivo. In a murine model of allergic asthma, GL significantly suppressed the cardinal features of asthma, such as airway hyperresponsiveness, eosinophilia and mucus production, after sensitization and subsequent challenge with ovalbumin (OVA). These changes resulted in induction of IL-12p70 and IL-10 production by lung CD11c+ dendritic cells (DCs) accompanied by an increase of IL-3 receptor α chain and indoleamine-2,3-dioxygenase expression in these cells. Furthermore, GL inhibited IL-4 production in T-bet-deficient CD4+ T cells and down-regulated the suppressor of cytokine signaling-3 (SOCS-3), also in the absence of STAT-3 in T cells, in the lung in a murine model of asthma. In addition, we found reduced amounts of pSTAT-5 in the lung of GL-treated mice that correlated with decreased release of IL-2 by lung OVA-specific CD4+ T cells after treatment with GL in vitro also in the absence of T-bet. Thus, GL treatment in vivo and in vitro emerges as a novel therapeutic approach for allergic asthma by modulating lung DC phenotype and function resulting in a protective response via CD4+FoxP3+ regulatory T cells locall

How Do Young Adults Prefer to Access Mental Health Information?

KT strategies for sharing mental health information need to include both active and passive options for young adults. This includes the use of both old and new media tools.York’s Knowledge Mobilization Unit provides services and funding for faculty, graduate students, and community organizations seeking to maximize the impact of academic research and expertise on public policy, social programming, and professional practice. It is supported by SSHRC and CIHR grants, and by the Office of the Vice-President Research & Innovation. [email protected] www.researchimpact.c

Comprehensive Assessment of the Potential for Efficient District Heating and Cooling and for High-Efficient Cogeneration in Austria

In accordance with the EU Energy Efficiency Directive all Member States have to develop a comprehensive assessment of the potential for high-efficient CHP and efficient district heating and cooling by the end of 2015. This paper describes the approach and methodology used to determine the district heating potentials for Austria. In a first step actual and future heating and cooling demand in the building sector is evaluated using the techno-economic bottom-up model Invert/EE-Lab. Relevant infrastructure probably existing in 2025 is investigated and included into the analysis. Technical potentials for efficient technologies are calculated. After a classification of relevant regions into main and secondary regions a country-level cost-benefit-analysis is performed. The results indicate that there is a reasonable additional potential for district heating by the year 2025 under our central scenario assumptions and within sensitivity scenarios. Only in scenarios with high CO2-price or low gas price, CHP is an economically efficient solution to supply district heat

A short isoform of STIM1 confers frequency-dependent synaptic enhancement

Store-operated Ca2+-entry (SOCE) regulates basal and receptor-triggered Ca2+ signaling with STIM proteins sensing the endoplasmic reticulum (ER) Ca2+ content and triggering Ca2+ entry by gating Orai channels. Although crucial for immune cells, STIM1’s role in neuronal Ca2+ homeostasis is controversial. Here, we characterize a splice variant, STIM1B, which shows exclusive neuronal expression and protein content surpassing conventional STIM1 in cerebellum and of significant abundance in other brain regions. STIM1B expression results in a truncated protein with slower kinetics of ER-plasma membrane (PM) cluster formation and ICRAC, as well as reduced inactivation. In primary wild-type neurons, STIM1B is targeted by its spliced-in domain B to presynaptic sites where it converts classic synaptic depression into Ca2+- and Orai-dependent short-term synaptic enhancement (STE) at high-frequency stimulation (HFS). In conjunction with altered STIM1 splicing in human Alzheimer disease, our findings highlight STIM1 splicing as an important regulator of neuronal calcium homeostasis and of synaptic plasticity