Inhibition of SUMOylation Induces Adaptive Antitumor Immunity against Pancreatic Cancer through Multiple Effects on the Tumor Microenvironment.

Improvement of outcome in patients with pancreatic ductal adenocarcinoma (PDAC) requires exploration of novel therapeutic targets. Thus far, most studies of PDAC therapies, including those inhibiting small ubiquitin-like modifications (SUMOylation), have focused on PDAC epithelial cell biology, yet SUMOylation occurs in a variety of cell types. The mechanisms by which SUMOylation impacts PDAC in the context of its tumor microenvironment are poorly understood.

Measurement and control of foam generation in a mammalian cell culture.

Foam is generated in mammalian cell cultures by excessive agitation or gas sparging. This occurs particularly in cultures that generate recombinant proteins at high cell concentrations. Three antifoam agents were tested for their compatibility with antibody-producing Chinese hamster ovary (CHO) cells.

Pressure-Enabled Drug Delivery (PEDD) of a class C TLR9 agonist in combination with checkpoint inhibitor therapy in a murine pancreatic cancer model.

Background: Systemic immunotherapy has had limited clinical benefit in pancreatic ductal adenocarcinoma. This is thought to be due to its desmoplastic immunosuppressive tumor microenvironment in addition to high intratumoral pressures that limit drug delivery. Recent preclinical cancer models and early-phase clinical trials have demonstrated the potential of toll-like receptor 9 agonists, including the synthetic CpG oligonucleotide SD-101, to stimulate a wide range of immune cells and eliminate suppressive myeloid cells.

Treatment of pancreatic cancer with irreversible electroporation and intratumoral CD40 antibody stimulates systemic immune responses that inhibit liver metastasis in an orthotopic model.

Background: Pancreatic cancer (PC) has a poor prognosis, and most patients present with either locally advanced or distant metastatic disease. Irreversible electroporation (IRE) is a non-thermal method of ablation used clinically in locally advanced PC, but most patients eventually develop distant recurrence. We have previously shown that IRE alone is capable of generating protective, neoantigen-specific immunity.

Oxaliplatin-induced peripheral neuropathy can be minimized by pressurized regional intravascular delivery in an orthotopic murine pancreatic cancer model.

Purpose: There is a great need to reduce the toxicity of chemotherapy used in the management of pancreatic ductal adenocarcinoma (PDAC). Here we explore if regional pressurized delivery of oxaliplatin can minimize peripheral neuropathy in mice.

Methods: We used an orthotopic PDAC mouse model and delivered a single dose of oxaliplatin through the portal vein using a pressure-enabled system (pancreatic retrograde venous infusion, PRVI).

Pressure-enabled delivery of gemcitabine in an orthotopic pancreatic cancer mouse model.

Background: We describe the use of pancreatic retrograde venous infusion in an orthotopic murine model of pancreatic ductal adenocarcinoma and hypothesize that pancreatic retrograde venous infusion delivery of gemcitabine will increase concentrations of gemcitabine in the tumor and the subsequent tumor response to treatment.

Methods: Murine pancreatic ductal adenocarcinoma (KPC4580P) was transplanted onto the pancreatic tail of C57BL/6J mice. Groups (n = 15) of mice were assigned to sham laparotomy and 100 mg/kg intraperitoneal infusion of gemcitabine (systemic gemcitabine), pancreatic venous isolation with pancreatic retrograde venous infusion of 100 mg/kg gemcitabine, or pancreatic retrograde venous infusion with saline infusion.

Anti-KIT DNA Aptamer for Targeted Labeling of Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumor (GIST), the most common sarcoma, is characterized by KIT protein overexpression, and tumors are frequently driven by oncogenic mutations. Targeted inhibition of KIT revolutionized GIST therapy and ushered in the era of precision medicine for the treatment of solid malignancies. Here, we present the first use of a KIT-specific DNA aptamer for targeted labeling of GIST.

Gold foil-based biosensor for the determination of hydrogen peroxide.

Hydrogen peroxide ($\text{H}_{\mathbf {2}} \mathbf {O} _{\mathbf {2}}$) plays a critical role in the regulation of multifarious physiological processes. We developed a sensor containing a mercaptopropionic acid (MPA) monolayer covalently immobilized with Horseradish peroxidase (HRP) enzyme for the electrochemical detection of hydrogen peroxide ($\textbf{H}_{\mathbf {2}} \mathbf {O} _{\mathbf {2}}$). A gold foil substrate was chemically treated with nitric acid and were used as working electrode.

Fabrication of highly effective hybrid biofuel cell based on integral colloidal platinum and bilirubin oxidase on gold support.

A hybrid biofuel cell (HBFC) is explored as a low-cost alternative to abiotic and enzymatic biofuel cells. Here the HBFC provides an enzymeless approach for the fabrication of the anodic electrode while employing an enzymatic approach for the fabrication of the cathodic electrode to develop energy harvesting platform to power bioelectronic devices. The anode employed 250 μm braided gold wire modified with colloidal platinum (Au-co-Pt) and bilirubin oxidase (BODx) modified gold coated Buckypaper (BP-Au-BODx) cathode.

A Syngeneic Pancreatic Cancer Mouse Model to Study the Effects of Irreversible Electroporation.

Pancreatic cancer (PC), a disease which kills approximately 40,000 patients each year in the US, has successfully evaded several therapeutic approaches including the promising immunotherapeutic strategies. Irreversible electroporation (IRE) is a non-thermal ablation technique that induces tumor cell death without destruction of adjacent collagenous structures, thus enabling the procedure to be performed in tumors very close to blood vessels. Unlike thermal ablation techniques, IRE results in gradual apoptotic cell death, along with immediate ablation induced necrosis, and is currently in clinical use for selected patients with locally advanced PC.

Sandwiching spherical 1,2-dioleoyltrimethylammoniumpropane liposome in gold nanoparticle on solid transducer for electrochemical ultrasensitive DNA detection and transfection.

Cationic N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium propane (DOTAP) liposome is spherically sandwiched in gold nanoparticle (abbreviated as sDOTAP-AuNP) onto a gold electrode surface. The sDOTAP-AuNP is applied for electrochemical label free DNA sensing and Escherichia coli cell transfection for the first time. Complementary target (named as hybridized), non-complementary target (un-hybridized) and single base mismatch target (named as SMM) hybridized surfaces are discriminated sensitively and selectively in presence of [Fe(CN)6](3-/4-).

Gold surface supported spherical liposome-gold nano-particle nano-composite for label free DNA sensing.

Immobilization of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) liposome-gold nano-particle (DOPE-AuNP) nano-composite covalently on 3-mercaptopropionic acid (MPA) on gold surface is demonstrated for the first time for electrochemical label free DNA sensing. Spherical nature of the DOPE on the MPA monolayer is confirmed by the appearance of sigmoidal voltammetric profile, characteristic behavior of linear diffusion, for the MPA-DOPE in presence of [Fe(CN)(6)](3-/4-) and [Ru(NH(3))(6)](3+) redox probes. The DOPE liposome vesicle fusion is prevented by electroless deposition of AuNP on the hydrophilic amine head groups of the DOPE.

Validation and divergence of the activation energy barrier crossing transition at the AOT/lecithin reverse micellar interface.

In this report, the validity and divergence of the activation energy barrier crossing model for the bound to free type water transition at the interface of the AOT/lecithin mixed reverse micelle (RM) has been investigated for the first time in a wide range of temperatures by time-resolved solvation of fluorophores. Here, picosecond-resolved solvation dynamics of two fluorescent probes, ANS (1-anilino-8-naphthalenesulfonic acid, ammonium salt) and Coumarin 500 (C-500), in the mixed RM have been carefully examined at 293, 313, 328, and 343 K. Using the dynamic light scattering (DLS) technique, the size of the mixed RMs at different temperatures was found to have an insignificant change.

Direct conjugation of semiconductor nanocrystals to a globular protein to study protein-folding intermediates.

In this Article, we study the development of semiconductor nanocrystals (quantum dots of average diameter less than 2 nm) directly conjugated to a transporter protein human serum albumin (HSA) as fluorescent biological labels. Förster resonance energy transfer (FRET) from the amino acid tryptophan (Trp214) to quantum dot in HSA is monitored to follow the local and global changes in the protein structure during thermal unfolding and refolding processes. This study is likely to attract widespread attention as a powerful tool for the study of protein folding.

Nonspecific protein-DNA interactions: complexation of alpha-chymotrypsin with a genomic DNA.

In this contribution, we report studies on nonspecific protein-DNA interactions of an enzyme protein bovine pancreatic alpha-chymotrypsin (CHT) with genomic DNA (from salmon testes) using two biologically common fluorescent probes: 1-anilinonaphthalene-8-sulfonate (ANS) and 2,6-p-toluidinonaphthalene sulfonate (TNS). TNS molecules that are nonspecifically bound to positively charged basic residues at the surface sites, not in the hydrophobic cavities of the protein, are preferentially displaced upon complexation of TNS-labeled CHT with DNA. The time-resolved fluorescence anisotropy of TNS molecules bound to hydrophobic cavities/clefts of CHT reveals that global tumbling motion of the protein is almost frozen in the protein-DNA complex.

Aggregated CdS quantum dots: Host of biomolecular ligands.

In this contribution, we have studied structural and photophysical properties of aggregated CdS quantum dots (QDs) capped with 2-mercaptoethanol in aqueous medium. The hydrodynamic diameter of the nanostructures in aqueous solution was found to be approximately 160 nm with the dynamic light scattering (DLS) technique, which is in close agreement with atomic force microscopy (AFM) studies (diameter approximately 150 nm). However, the UV-vis absorption spectroscopy, powder X-ray diffraction (XRD), and transmission electron microscopy (TEM) studies confirm the average particle size (QD) in the nanoaggregate to be 4.

Direct observation of protein folding in nanoenvironments using a molecular ruler.

We observe folding of horse heart cytochrome c in various environments including nano-compartments (micelles and reverse micelles). Using picosecond-resolved Förster resonance energy transfer (FRET) dynamics of an extrinsic covalently attached probe dansyl (donor) at the surface of the protein to a heme group (acceptor) embedded inside the protein, we measured angstrom-resolved donor-acceptor distances in the environments. The overall structural perturbations of the protein revealed from the FRET experiments are in close agreement with our circular dichroism (CD) and dynamic light scattering (DLS) studies on the protein in a variety of solution conditions.