A Time to Kill: Targeting Apoptosis in Cancer

The process of apoptosis is essential for maintaining the physiologic balance between cell death and cell growth. This complex process is executed by two major pathways that participate in activating an executioner mechanism leading to chromatin disintegration and nuclear fragmentation. Dysregulation of these pathways often contributes to cancer development and resistance to cancer therapy. Here, we review the most recent discoveries in apoptosis regulation and possible mechanisms for resensitizing tumor cells to therapy.     

Dendritic Cells Pulsed with Cytokine-Adjuvanted Tumor Membrane Vesicles Inhibit Tumor Growth in HER2-Positive and Triple Negative Breast Cancer Models

Dendritic cells (DCs) are the most effective antigen presenting cells for the development of T cell responses. The only FDA approved DC-based immunotherapy to date is Sipuleucel-T, which utilizes a fusion protein to stimulate DCs ex vivo with GM-CSF and simultaneously deliver the antigen PAP for prostate cancer. This approach is restricted by the breadth of immunity elicited to a single antigen, and to cancers that have a defined tumor associated antigen. Other multi-antigen approaches have been restricted by poor efficacy of vaccine adjuvants. We have developed a vaccine platform that consists of autologous DCs pulsed with cytokine-adjuvanted tumor membrane vesicles (TMVs) made from tumor tissue, that encapsulate the antigenic landscape of individual tumors. Here we test the efficacy of DCs pulsed with TMVs incorporated with glycolipid-anchored immunostimulatory molecules (GPI-ISMs) in HER2-positive and triple negative breast cancer murine models. Pulsing of DCs with TMVs containing GPI-ISMs results in superior uptake of vesicles, DC activation and cytokine production. Adaptive transfer of TMV-pulsed DCs to tumor bearing mice results in the inhibition of tumor growth, reduction in lung metastasis, and an increase in immune cell infiltration into the tumors. These observations suggest that DCs pulsed with TMVs containing GPI-GM-CSF and GPI-IL-12 can be further developed to be used as a personalized immunotherapy platform for cancer treatment.     

Capacitor-less induction heating system with self-resonant bifilar coil

In this work, a capacitor-less self-resonating coil-based induction heating (IH) system with magnetic resonant coupling has been proposed. In the conventional heating system, the inclusion of additional capacitor for creating the resonance results in poor efficiency of overall system. To overcome this issue, a bifilar coil system is implemented, which leads to series resonance at a particular frequency. The key mechanism is self-resonance wireless power transfer concept to IH system; hence, no capacitor is needed in the system. The coil has a series association of the coil inductance and capacitance at the resonant operating condition. A mathematical modeling and steady state analysis is performed for the conventional (solenoidal) coil and bifilar coil to estimate the actual value of the capacitance and inductance of the coil. The performance of the bifilar coil system is tested through COMSOL multiphysics simulation tool and parameters like eddy current, magnetic flux, and temperature distribution in the work piece are analyzed. The experimental setup of the bifilar coil-aided IH system is implemented with PIC16F877A microcontroller, and FLIR thermal imager is used to analyze the temperature distribution on the work piece. The experimental results are compared with the simulation results, and the bifilar coil system provides a promising solution.