Role of Apoptosis in Cancer Resistance to Chemotherapy

Cancer is a leading cause of death in human beings. Surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy are common modalities for cancer treatment. However, cancer resistance is common in chemotherapy and often leads to therapeutic failure. This chapter addresses the role of apoptosis in tumor’s resistance to chemotherapy and the underlying mechanisms. Cancer cells are always resistant to apoptotic signals via a series of biochemical changes. Cancer cells are resistant to chemotherapeutic agents that are potent apoptosis inducers via multiple mechanisms, such as upregulated anti-apoptotic signals and downregulated pro-apoptotic signals, faulty apoptotic signaling, faulty apoptosis initiation and implementation, etc. We also discuss the possible approaches to overcoming cancer resistance to chemotherapy due to altered apoptosis

Synthesis of small silver nanocubes in a hydrophobic solvent by introducing oxidative etching with Fe(III) species

The role of oxidative etching in the synthesis of noble-metal nanocrystals with a hydrophilic solvent (in particular, ethylene glycol) has been explored in our previous work. In this paper, we demonstrate that the mechanism of oxidative etching could be extended to the synthesis of single-crystal Ag nanocrystals in a hydrophobic solvent such as isoamyl ether. In this case, Fe(III) species in the form of FeCl3 or Fe(acac)(3) had to be introduced into the hydrophobic system as an effective etching agent. The final product contained single-crystal Ag nanocubes (slightly truncated) with an edge length as small as similar to 13.5 nm, a size that has been difficult to achieve using a hydrophilic system. The role of oxidative etching in the synthesis of noble-metal nanocrystals with a hydrophilic solvent (in particular, ethylene glycol) has been explored in our previous work. In this paper, we demonstrate that the mechanism of oxidative etching could be extended to the synthesis of single-crystal Ag nanocrystals in a hydrophobic solvent such as isoamyl ether. In this case, Fe(III) species in the form of FeCl3 or Fe(acac)(3) had to be introduced into the hydrophobic system as an effective etching agent. The final product contained single-crystal Ag nanocubes (slightly truncated) with an edge length as small as similar to 13.5 nm, a size that has been difficult to achieve using a hydrophilic system.NSF [DMR-0804088, ECS-0335765]; NIH [DP1 OD000798]; China Scholarship Counci

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

An Update on the Potential of Mesenchymal Stem Cell Therapy for Cutaneous Diseases

Mesenchymal stem or stromal cells (MSCs) are nonhematopoietic postnatal stem cells with self-renewal, multipotent differentiation, and potent immunomodulatory and anti-inflammatory capabilities, thus playing an important role in tissue repair and regeneration. Numerous clinical and preclinical studies have demonstrated the potential application of MSCs in the treatment of tissue inflammation and immune diseases, including inflammatory skin diseases. Therefore, understanding the biological and immunological characteristics of MSCs is important to standardize and optimize MSC-based regenerative therapy. In this review, we highlight the mechanisms underlying MSC-mediated immunomodulation and tissue repair/regeneration and present the latest development of MSC-based clinical trials on cutaneous diseases

Au-I: an alternative and potentially better precursor than Au-III for the synthesis of Au nanostructures

NSF [DMR-0804088, ECS-0335765]; Washington University; China Scholarship CouncilThis article provides an overview of current developments with regard to the use of Au-I compounds as precursors in the synthesis of Au nanostructures with controlled shapes or morphologies. We begin with a brief description of the difference between Au-I and Au-III compounds, followed by a discussion on how the solubility and stability of a Au-I compound can be improved by forming a coordination complex with a ligand (X). We then focus on a range of recent studies that have been directed towards the use of Au-I-X complexes as precursors to elemental Au, in an effort to produce Au nanostructures with a variety of shapes, including icosahedral nanoparticles, truncated decahedrons, nanowires or nanorods, branched nanostructures, hybrid nanostructures, nanoboxes, nanocages, and nanoframes. In these syntheses, the Au-I-X complexes offer a number of attractive features for generating Au nanostructures as compared to the conventional Au-III compounds, mostly due to their differences in oxidation state and aurophilic effect. The ability to control Au-I chemistry therefore provides a great opportunity to systematically investigate the syntheses, physical properties, and applications of Au nanostructures

Research on a Novel Locating Method for Track Inspection Based on Onboard Sensors in Maglev Train

Guideway inspection is of great significance to the operation safety and riding quality of a commercial high-speed maglev transportation system. When analyzing guideway inspection data, it is important to obtain the location information for each piece of raw data and convert it from the time domain to the spatial domain for the analysis afterward. Previous studies have used the method of adding additional hardware such as GPS (global positioning system) receivers, LRF (location reference flag) readers, or onboard CAN (controller area network) bus adaptors to obtain location information. This paper presents a novel method for indirectly obtaining the location information via the use of data from the levitation and guidance control sensors perpendicular to the longitudinal direction to extract the characteristic information from the track. The method can be used for a long stator linear motor-driven maglev system and similar contactless rail transit systems. The results showed that the method could accurately identify the required location information in each stator tooth during the entire operation simultaneously with the operating information such as train velocity, direction, and track ID, without additional hardware installation and vehicle network connection. Thus, it could improve the pertinence of the results of guideway inspection equipment, and at the same time, facilitate the miniaturization and independence of guideway inspection equipment

Research on On-Line Detection Method of Transformer Winding Deformation Based on VFTO

At present, the detection of transformer winding deformation faults is carried out in an offline state, which requires the transformer to cooperate with the implementation of planned power outages, or it takes place after the sudden failure of the transformer when it is out of operation. It is difficult to obtain the status information of the windings online in time. Since the transformer will suffer very fast transient overvoltage (VFTO) impact during operation, combined with the principle of the frequency response method, an online detection method of transformer winding deformation based on VFTO is proposed. In order to study the frequency response characteristics of transformer winding under the impact of VFTO, the generation process of VFTO is simulated by simulation software, and the equivalent circuit model of transformer winding before and after deformation is established. The VFTO signal is injected into the transformer circuit model as an excitation source, and the changes of resonant frequencies of frequency response curve under different deformation types and different deformation degrees of winding are analyzed. The simulation results show that the frequency response curves of different winding deformation types are different. Different deformation degrees are simulated by increasing the radial capacitance by 4%, 13%, and 23%, series inductance by 2%, 4%, and 6%, and longitudinal capacitance by 3%, 6%, and 9%, and the change of resonance frequencies can comprehensively reflect the deformation information of winding. At the same time, the tests of different deformation types and deformation degrees of the simulated winding are carried out. The results show that with the deepening of the change degree of the simulated fault inductance value, the frequency response curve shifts to the low-frequency direction, confirming the feasibility of the online detection method of transformer winding deformation based on VFTO