MICA-G129R: A bifunctional fusion protein increases PRLR-positive breast cancer cell death in co-culture with natural killer cells.

Breast cancer cells were reported to up-regulate human prolactin receptor (PRLR) to assist their growth through the utilization of prolactin (PRL) as the growth factor, which makes PRLR a potential therapeutic target for breast cancer. On the other hand, advanced cancer cells tend to down-regulate or shed off stress signal proteins to evade immune surveillance and elimination. In this report, we created a fusion protein consisting of the extracellular domain of MHC class I chain-related protein (MICA), a stress signal protein and ligand of the activating receptor NKG2D of natural killer (NK) cells, and G129R, an antagonistic variant of PRL.

Rapid isolation of lentivirus particles from cell culture media via a hydrophobic interaction chromatography method on a polyester, capillary-channeled polymer fiber stationary phase.

Lentiviruses are increasingly used as gene delivery vehicles for vaccines and immunotherapies. However, the purification of clinical-grade lentivirus vectors for therapeutic use is still troublesome and limits preclinical and clinical experiments. Current purification methods such as ultracentrifugation and ultrafiltration are time consuming and do not remove all of the impurities such as cellular debris, membrane fragments, and denatured proteins from the lentiviruses.

Expression-based prediction of human essential genes and candidate lncRNAs in cancer cells.

Motivation: Essential genes are required for the reproductive success at either cellular or organismal level. The identification of essential genes is important for understanding the core biological processes and identifying effective therapeutic drug targets. However, experimental identification of essential genes is costly, time consuming and labor intensive.

Bioactive Sesquiterpene Lactones Isolated from the Whole Plants of .

Twelve sesquiterpene lactones were isolated from the whole plants of . These included eight new compounds, vercinolides A-H (-), along with four known substances (-). The structures of the new compounds were determined by 1D and 2D NMR experiments and mass spectrometric methods.

Lentiviral delivery of novel fusion protein IL12/FasTI for cancer immune/gene therapy.

Many of the cytokine-based cancer immunotherapies are hindered by the devastating side effects of systemic delivery of the cytokines. To address this problem, we previously described a novel approach to locally achieve high doses of interleukin-12 (IL-12) in tumors and demonstrated that bi-functional fusion protein mIL-12/FasTI expressed by stable clones of TC-1 cells efficiently suppressed tumor proliferation by activating natural killer (NK) cells and other cytolytic killer cells and sending apoptotic signals into tumor cells. In the present study, we employed a lentiviral vector-based gene delivery system to deliver this fusion construct directly into tumor cells.

Investigation of composition, structure and bioactivity of extracellular polymeric substances from original and stress-induced strains of Thraustochytrium striatum.

This paper was the first to study extracellular polymeric substances (EPSs) of Thraustochytrium striatum on composition, structure and bioactivities. Two strains of T. striatum including original (ori) and high-biomass (mut) strains (induced by high-nitrogen stress) were compared.

MHC class I chain-related A: Polymorphism, regulation and therapeutic value in cancer.

MICA and MICB are stress-induced molecules recognized by NKG2D, one of major activation receptors of natural killer (NK) cells. Upon binding to NKG2D, NKG2D-mediated cytolytic immune response of immune effector cells will be activated against virally infected and tumor cells expressing MICA. In the early oncogenic development, membrane-bound MICA serves as a key signal to recruit anti-tumor immune effectors.

Fusion Proteins of NKG2D/NKG2DL in Cancer Immunotherapy.

NKG2D (natural killer group 2, member D) is an important activating receptor in natural killer (NK) cells and some T cells. NKG2D ligands (NKG2DLs) are specifically expressed on most tumor cells. The engagement of these ligands on tumor cells to NKG2D on NK cells will induce cell-mediated cytotoxicity and have target cells destroyed.

MICA/IL-12: A novel bifunctional protein for killer cell activation.

Natural killer (NK) cells have the potential to be effective killers of tumor cells. They are governed by inhibitory and activating receptors such as NKG2D, whose ligands are normally upregulated in cells that are stressed, like cancer cells. Advanced cancer cells, however, have ways to reduce the expression of these ligands, leaving them less detectable by NK cells.

Bovine serum albumin coated nanoparticles for in vitro activated fluorescence.

A fluorophore modified nanoparticle was developed that can only fluoresce when a specific environmental parameter interacts with the system. The model system consisted of an azide modified bovine serum albumin (azBSA) that had been covalently attached to an alkyne modified silicon phthalocyanine (alSiPc) derivative through a copper catalyzed azide/alkyne Huisgen cycloaddition (click reaction). The azBSA/alSiPc assembly was then clicked to a ca.

Anti-inflammatory and Quinone Reductase Inducing Compounds from Fermented Noni (Morinda citrifolia) Juice Exudates.

A new fatty acid ester disaccharide, 2-O-(β-d-glucopyranosyl)-1-O-(2E,4Z,7Z)-deca-2,4,7-trienoyl-β-d-glucopyranose (1), a new ascorbic acid derivative, 2-caffeoyl-3-ketohexulofuranosonic acid γ-lactone (2), and a new iridoid glycoside, 10-dimethoxyfermiloside (3), were isolated along with 13 known compounds (4-16) from fermented noni fruit juice (Morinda citrifolia). The structures of the new compounds, together with 4 and 5, were determined by 1D and 2D NMR experiments, as well as comparison with published values. Compounds 2 and 7 showed moderate inhibitory activities in a TNF-α-induced NF-κB assay, and compounds 4 and 6 exhibited considerable quinone reductase-1 (QR1) inducing effects.

Mouse interleukin-12/FasTI: A novel bi-functional fusion protein for cancer immuno/gene therapy.

Whereas cancer immunotherapy with cytokines in recent research was demonstrated effective in activating immune response against tumor cells, one major obstacle with the use of these cytokines is their severe side effects when delivered systemically at high doses. Another challenge is that advanced tumor cells often evade immunosurveillance of the immune system as well as of the Fas-mediated apoptosis by various mechanisms. We report the design and preliminary evaluation of the antitumor activity of a novel fusion protein-mIL-12/FasTI, consisting of mouse interleukin-12 and the transmembrane and intracellular domains of mouse Fas.

Sequestering survivin to functionalized nanoparticles: a strategy to enhance apoptosis in cancer cells.

Survivin belongs to the family of inhibitor of apoptosis proteins (IAP) and is present in most cancers while being below detection limits in most terminally differentiated adult tissues, making it an attractive protein to target for diagnostic and, potentially, therapeutic roles. Sub-100 nm poly(propargyl acrylate) (PA) particles were surface modified through the copper-catalyzed azide/alkyne cycloaddition of an azide-terminated survivin ligand derivative (azTM) originally proposed by Abbott Laboratories and speculated to bind directly to survivin (protein) at its dimer interface. Using affinity pull-down studies, it was determined that the PA/azTM nanoparticles selectively bind survivin and the particles can enhance apoptotic cell death in glioblastoma cell lines and other survivin over-expressing cell lines such as A549 and MCF7 relative to cells incubated with the original Abbott-derived small molecule inhibitor.

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).

A biotin-streptavidin-biotin bridge dramatically enhances cell fusion.

Although the generation of hybrid cells by cell fusion plays a significant role in biotechnology and biomedicine, the low cell-fusion rates and the limitation of large-scale cell fusion for clinical applications of the two widely used approaches, polyethylene-glycol (PEG)-mediated cell fusion and electrofusion, hinder the application of this critical technology in certain key areas, including cancer immunotherapy. In the present study, a simple procedure that can not only significantly increase the heterologous cell fusion but is also capable of producing fused cells on a large scale is reported. A biotin-streptavidin-biotin (BSB) bridge was created by coating one to-be-fused cell with biotin and the other with biotin-streptavidin.

Antitumor activity of fermented noni exudates and its fractions.

Noni has been extensively used in folk medicine by Polynesians for over 2000 year. Recent studies have shown that noni has a wide spectrum of therapeutic activities including inhibition of angiogenesis, anti-inflammatory effects and anti-cancer activities. Intraperitoneal (i.

An IL-12/Shh-C domain fusion protein-based IL-12 autocrine loop for sustained natural killer cell activation.

The dependency of activated natural killer (NK) cells on the continuous support of exogenous interleukin (IL)-2 for their in vivo survival, tumor localization and consequently, their antitumor effect, is a major obstacle for NK cell-mediated tumor therapy. In the present study, a fusion gene between IL-12 and mouse sonic hedgehog C-terminal domain (Shh-C) was constructed. The fusion protein was autocatalytically processed to form cholesterol-modified IL-12 molecules and an autocrine loop of IL-12 was established for the sustained activation of NK cells.

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.

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.

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.

Fusion induced reversal of dendritic cell maturation: an altered expression of inflammatory chemokine and chemokine receptors in dendritomas.

Dendritic cell-mediated cancer immunotherapy employs several ways to engage tumor antigens. We have demonstrated in both pre-clinical animal studies and early clinical trials that dendritomas, highly purified hybrids between dendritic cells (DC) and tumor cells, are superior activators of anti-tumor immunity. It has been argued, however, that DC vaccines may be dysfunctional in lymph node migration.

Laser-guidance based detection of cells with single-gene modification.

An optical method with single-gene sensitivity for cell detection based on laser guidance was explored. Guided by the optical force from a weakly focused laser beam, a cell will move along the laser axis. Cells with different properties experience different optical forces and thus guidance speeds.

Expression of CD226 antagonizes apoptotic cell death in murine thymocytes.

CD226 is known to be expressed on many types of peripheral lymphoid cells and involved in T cell differentiation, activation, and cytotoxicity. In this study, we report that CD226 is also expressed on mouse thymocytes at varying developmental stages, and its expression is associated with resistance of thymocytes to apoptosis. The levels of CD226 expression appeared to be closely coupled with thymocyte development, in that it was preferentially expressed on CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes at all stages during mouse development, and was markedly increased on the cells in neonatal mice.