Metronomic cyclophosphamide activation of anti-tumor immunity: tumor model, mouse host, and drug schedule dependence of gene responses and their upstream regulators.

Background: Cyclophosphamide (CPA) can activate immunogenic tumor cell death, which induces immune-based tumor ablation and long-term anti-tumor immunity in a syngeneic C57BL/6 (B6) mouse GL261 glioma model when CPA is given on a 6-day repeating metronomic schedule (CPA/6d). In contrast, we find that two other syngeneic B6 mouse tumors, LLC lung carcinoma and B16F10 melanoma, do not exhibit these drug-induced immune responses despite their intrinsic sensitivity to CPA cytotoxicity.

Methods: To elucidate underlying mechanisms, we investigated gene expression and molecular pathway changes associated with the disparate immune responsiveness of these tumors to CPA/6d treatment.

CpG-1826 immunotherapy potentiates chemotherapeutic and anti-tumor immune responses to metronomic cyclophosphamide in a preclinical glioma model.

Cyclophosphamide administered on an intermittent metronomic schedule induces strong immune-dependent regression in several glioma models. Here we investigate whether this immunogenic chemotherapy can be potentiated by combination with the immune stimulatory TLR9 agonist CpG-1826. CpG-1826 treatment of GL261 gliomas implanted in immune competent mice induced tumor growth delay associated with increased tumor recruitment of macrophages and B cells.

Reducing readmissions using teach-back: enhancing patient and family education.

This article describes a quality improvement initiative, implemented by a patient education workgroup within a tertiary Magnet® facility. The project focused on the association between inadequate care transitions in patients with heart failure and subsequent costly readmissions. The teach-back initiative was piloted with patients hospitalized with heart failure, because of this population's high risk of readmission.

Formalizing an integrative, multidisciplinary cancer therapy discovery workflow.

Although many clinicians and researchers work to understand cancer, there has been limited success to effectively combine forces and collaborate over time, distance, data, and budget constraints. Here we present a workflow template for multidisciplinary cancer therapy that was developed during the 2nd Annual Workshop on Cancer Systems Biology sponsored by Tufts University, Boston, Massachusetts, in July 2012. The template was applied to the development of a metronomic therapy backbone for neuroblastoma.