Yanzhang Wei

Apoptosis of lung carcinoma cells induced by a flexible optical fiber-based cold microplasma.

Atmospheric pressure plasmas have been used as a therapy for cancer. However, the fairly large size and rigidity of present plasma-delivery systems obstructs the precise treatment of tumors in harder-to-reach internal organs such as the lungs, pancreas, and duodenum. In order to improve the targeted delivery of plasmas a highly flexible microplasma jet device is fabricated using a hollow-core optical fiber with an inner diameter of either 15 μm, 55 μm, or 200 μm. Described herein, based on this device, are results on lung carcinoma therapy using a microplasma cancer endoscope. Despite the small inner diameter and the low gas flow rate, the generated plasma jets are shown to be sufficiently effective to induce apoptosis, but not necrosis, in both cultured mouse lung carcinoma and fibroblast cells. Further, the lung carcinoma cells were found to be more sensitive to plasma treatment than the fibroblast cells based on the overall plasma dose conditions. This work enables directed cancer therapies using on highly flexible and precise hollow optical fiber-based plasma device and offers enhancements to microplasma cancer endoscopy using an improved method of plasma targeting and delivery.

A flexible cold microplasma jet using biocompatible dielectric tubes for cancer therapy

This paper describes a flexible microplasma jet device using a Tygon® S-54-HL tube as a biocompatible tube and its potential in developing cancer therapies. The optical and physical properties of the plasma jets and preliminary apoptosis data of cultured murine tumor cells and nontumor fibroblast cells treated with these plasma jets are presented. Microplasma jets were observed to induce apoptosis in cultured murine cells in a dose-dependent manner. The murine melanoma tumor cells were more sensitive to plasma treatment than fibroblast cells. These features allow the direct and precise application of this microplasma jet device to tumor cells.

Single‐Cell‐Level Microplasma Cancer Therapy

A flexible microplasma endoscope based on a 15 μm hollow-core glass optical fiber is fabricated, and tumor cell apoptotic analysis supports its potential use in targeted cancer therapies. The optical-fiber microplasma jet reveals antitumor activity at a certain plasma dose in animal studies.

15-μm-sized single-cellular-level and cell-manipulatable microplasma jet in cancer therapies

The authors describe a proposed 15-μm-sized, single-cellular-level, and cell-manipulatable microplasma jet device with a microcapillary glass tip and its potential in the development of cancer treatment therapies. The electrical and optical properties of the plasma jets and preliminary apoptosis results of cultured murine tumor cells and non-tumor fibroblast cells treated with the plasma jets are presented. The generated plasma jet was stable and enabled the treatment of cultured cells in cell culture plates regardless of the small inner diameter and low gas flow rate. The microplasma jet was observed inducing apoptosis in cultured murine melanoma tumor cells in a dose-dependent manner. Furthermore, the percentage of apoptotic cells of murine melanoma tumor cells induced by this plasma device was approximately 2.5 times bigger than that of murine fibroblast cells as indicated by an Annex V apoptosis assay. The apoptosis in cultured murine tumor cells by the 15-μm-sized single-cellular-level and cell-manipulatable microplasma jet device was also observed using an in situ apoptosis assay. We report on a novel microplasma jet device with the advantages of single-cellular-level and single cell-manipulatable plasma treatment with precise and solid stimuli. This highly precise plasma medicine, which enables new directed cancer therapies can be combined with current cell manipulation and cell culturing technologies without much difficulty.

Single-cell-level cancer therapy using a hollow optical fiber-based microplasma.

Atmospheric-pressure plasmas have been used in cancer therapies, but the size of the delivery systems precludes single-cell treatments. Plasmas are gaseous collections of ionized particles that include free electrons and radicals that are short-lived but strongly reactive species. Cancer therapies based on plasmas that operate at atmospheric pressure have been developed, which expose these free radicals to tumor cells causing their subsequent apoptosis at a rapid pace. To define the mechanism of plasma-induced tumor cell apoptosis, it would be preferred to have a plasma device that can treat tumor cells at the single-cell level. Thus, the challenge is to generate and deliver plasmas to a single cell. A microplasma jet device consisting of a tube with electrodes has been demonstrated as a source for creating nonthermal atmospheric-pressure plasmas with dimensions on the order of several hundred micrometers. There are two principal methods for reducing the size of the plasma. The first method utilizes a glass capillary tube with a small inner diameter. The second approach employs a thin metal wire as an electrode. Because microplasma jets were originally developed for superficial work (i.e., treating only the surface of objects),

Fusion protein from RGD peptide and Fc fragment of mouse immunoglobulin G inhibits angiogenesis in tumor.

Targeting tumor vasculature represents an interesting approach for the treatment of solid tumors. The αvβ3 integrins have been found to be specifically associated with angiogenesis in tumors. By using bacteriophage display technology, Ruoslahti et al found that a group of peptides containing the RGD (Arg-Gly-Asp) motif have high-binding affinity to the αvβ3 integrins in tumors. In this study, we designed a fusion protein containing the RGD sequence and the Fc fragment of mouse IgG in order to target the Fc portion of IgG to the tumor vasculature to elicit an antiangiogenesis immune response. In vivo angiogenesis and tumor studies demonstrated that the fusion protein (RGD/mFc) inhibited tumor angiogenesis and tumor growth and improved overall survival. This approach may generate new therapeutic agents for solid tumor treatment.

Cerebrospinal fluid extracellular vesicles undergo age dependent declines and contain known and novel non-coding RNAs.

Brain development requires precise orchestration of cellular events through the coordinate exchange of information between distally located cells. One mechanism by which intercellular communication is achieved is through the transfer of extracellular vesicles (EVs). Exosomes are EVs that carry lipids, nucleic acids, and proteins and are detectable in most biological fluids including cerebrospinal fluid (CSF). Here we report that CSF EV concentrations undergo age dependent fluctuations. We characterized EV RNA content by next generation small RNA sequencing and miRNA microarray analysis and identified a temporal shift in CSF EV content. CSF EVs encapsulated miRNAs that contain a conserved hnRNPA2/B1 recognition sequence. We found that hnRNPA2/B1-containing EVs were produced by choroid plexus epithelial cells and that hnRNPA2/B1 containing EVs decreased with age. These results provide insight into EV exchange of miRNAs within the central nervous system and a framework to understand how changes in EVs may have an important impact on brain development.

Synergistic anti‐tumor effect of glycosylphosphatidylinositol‐anchored IL‐2 and IL‐12

Preclinical and clinical studies have demonstrated that interleukin 2 (IL‐2), interleukin 12 (IL‐12), and some other cytokines, play important roles in activating host immune responses against tumor growth. However, severe side effects caused by systemic high‐dose administration of these cytokines limit their clinical application. In our previous study, local high doses of IL‐2 were achieved by a GPI‐anchoring technology; therefore, it will be interesting to know if this technology works for other cytokines.

Whole tumor cell vaccine with irradiated S180 cells as adjuvant

Whole tumor cell vaccines have been widely studied and remain promising cancer immunotherapies. In the present study, we discovered that vaccination with irradiated mouse sarcoma S180 tumor cells stimulated robust antitumor immunity to autologous tumor cells in both syngenic and allogenic mice. The antitumor activity requires both T and B cells, but not NK cells. When a mouse lung carcinoma (TC-1) whole tumor cell vaccine was combined with the S180 vaccine, the antitumor immunity against live TC-1 tumor cells is significantly enhanced compared to a TC-1 whole cell vaccine alone. This antitumor immunity not only prevents live tumor challenge but also eradicates existing tumor cells. A similar phenomenon was also observed when S180 vaccine was combined with LL2 Lewis lung carcinoma tumor cells. Therefore, S180 vaccine may serve as an adjuvant for other whole tumor cell vaccines.

Antitumor and anti-angiogenic activities of Scutellaria barbata extracts in vitro are partially mediated by inhibition of Akt/protein kinase B.

The Akt pathway is considered a pivotal player in regulating cell survival, growth, migration and angiogenesis. Disruption of normal Akt/PKB/PTEN signaling frequently occurs in numerous types of human cancers. Therefore, this signaling pathway is regarded as an important target for effective cancer therapeutic strategies. In the present study, methanol extracts from Scutellaria barbata (S. barbata) were determined to be Akt/protein kinase B inhibitory, after screening a panel of 40 traditional Chinese herbs with the Fast Activated Cell-based ELISA (FACE) assay. S. barbata extracts were found to suppress the phosphorylation levels of Akt. This inhibition was Akt kinase-specific as it had no effect on PI3K, the upstream kinase of Akt, whereas the levels of phosphorylated Bad and FHKR, the two downstream targets of Akt, changed as the levels of Akt changed. S. barbata extracts also exhibited cytotoxicity against LoVo and human umbilical vein endothelial cells (HUVECs). Furthermore, this extract inhibited the process of in vitro angiogenesis of HUVECs on Matrigel. S. barbata may be a suitable alternative source with which to isolate small molecules for use as Akt kinase inhibitors.