CRISPR-enhanced engineering of therapy-sensitive cancer cells for self-targeting of primary and metastatic tumors.

Tumor cells engineered to express therapeutic agents have shown promise to treat cancer. However, their potential to target cell surface receptors specific to the tumor site and their posttreatment fate have not been explored. We created therapeutic tumor cells expressing ligands specific to primary and recurrent tumor sites (receptor self-targeted tumor cells) and extensively characterized two different approaches using (i) therapy-resistant cancer cells, engineered with secretable death receptor-targeting ligands for "off-the-shelf" therapy in primary tumor settings, and (ii) therapy-sensitive cancer cells, which were CRISPR-engineered to knock out therapy-specific cell surface receptors before engineering with receptor self-targeted ligands and reapplied in autologous models of recurrent or metastatic disease.

Antiangiogenic variant of TSP-1 targets tumor cells in glioblastomas.

Three type-1 repeat (3TSR) domain of thrombospondin-1 is known to have anti-angiogenic effects by targeting tumor-associated endothelial cells, but its effect on tumor cells is unknown. This study explored the potential of 3TSR to target glioblastoma (GBM) cells in vitro and in vivo. We show that 3TSR upregulates death receptor (DR) 4/5 expression in a CD36-dependent manner and primes resistant GBMs to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced caspase-8/3/7 mediated apoptosis.

Evaluating the effect of therapeutic stem cells on TRAIL resistant and sensitive medulloblastomas.

Mesenchymal stem cells (MSC) are emerging as novel cell-based delivery agents; however, a thorough investigation addressing their therapeutic potential in medulloblastomas (MB) has not been explored to date. In this study, we engineered human MSC to express a potent and secretable variant of a tumor specific agent, tumor necrosis factor-apoptosis-inducing ligand (S-TRAIL) and assessed the ability of MSC-S-TRAIL mediated MB killing alone or in combination with a small molecule inhibitor of histone-deacetylase, MS-275, in TRAIL-sensitive and -resistant MB in vitro and in vivo. We show that TRAIL sensitivity/resistance correlates with the expression of its cognate death receptor (DR)5 and MSC-S-TRAIL induces caspase-3 mediated apoptosis in TRAIL-sensitive MB lines.

A first-generation multi-functional cytokine for simultaneous optical tracking and tumor therapy.

Creating new molecules that simultaneously enhance tumor cell killing and permit diagnostic tracking is vital to overcoming the limitations rendering current therapeutic regimens for terminal cancers ineffective. Accordingly, we investigated the efficacy of an innovative new multi-functional targeted anti-cancer molecule, SM7L, using models of the lethal brain tumor Glioblastoma multiforme (GBM). Designed using predictive computer modeling, SM7L incorporates the therapeutic activity of the promising anti-tumor cytokine MDA-7/IL-24, an enhanced secretory domain, and diagnostic domain for non-invasive tracking.

Folding induced assembly of polypeptide decorated gold nanoparticles.

Reversible assembly of gold nanoparticles controlled by the homodimerization and folding of an immobilized de novo designed synthetic polypeptide is described. In solution at neutral pH, the polypeptide folds into a helix-loop-helix four-helix bundle in the presence of zinc ions. When immobilized on gold nanoparticles, the addition of zinc ions induces dimerization and folding between peptide monomers located on separate particles, resulting in rapid particle aggregation.

Monoclonal antibody-based fluorescence polarization immunoassay for sulfamethoxypyridazine and sulfachloropyridazine.

In this paper, a new monoclonal antibody (Mab) against sulfamethoxypyridazine (SMP) was produced, and a fluorescence polarization immunoassay (FPIA) based on the produced Mab was developed and optimized for the qualitative screening analysis of SMP. The Mab was raised from mice immunized with SMP linked to bovine serum albumin (BSA) by carbodiimide activated ester formation, using a succinic anhydride spacer molecule between SMP and BSA. Fluorescein labeled sulfachloropyridazine (SCP) and SMP (tracer) were synthesized and purified by thin layer chromatography (TLC).

Rapid all-in-one three-step immunoassay for non-instrumental detection of ochratoxin A in high-coloured herbs and spices.

A feasible three-step method for ochratoxin A (OTA) rapid detection was developed and applied for OTA screening in high-coloured matrices such as liquorice, ginger, nutmeg, black pepper, white pepper and Capsicum spp. spices at a control level of 10mugkg(-1). The method was based on the clean-up tandem immunoassay column and involved three steps: extract application, washing step and application of chromogenic substrate.