Nano-Pulse Treatment Overcomes the Immunosuppressive Tumor Microenvironment to Elicit In Situ Vaccination Protection against Breast Cancer.

We previously reported that nano-pulse treatment (NPT), a pulsed power technology, resulted in 4T1-luc mammary tumor elimination and a strong in situ vaccination, thereby completely protecting tumor-free animals against a second live tumor challenge. The mechanism whereby NPT mounts effective antitumor immune responses in the 4T1 breast cancer predominantly immunosuppressive tumor microenvironment (TME) remains unanswered. In this study, orthotopic 4T1 mouse breast tumors were treated with NPT (100 ns, 50 kV/cm, 1000 pulses, 3 Hz).

The role of reactive oxygen species in the immunity induced by nano-pulse stimulation.

Reactive oxygen species (ROS) are byproducts of tumor cells treated with Nano-Pulse Stimulation (NPS). Recently, ROS have been suggested as a contributing factor in immunogenic cell death and T cell-mediated immunity. This research further investigated the role of NPS induced ROS in antitumor immunity.

Nano-Pulse Stimulation for the Treatment of Pancreatic Cancer and the Changes in Immune Profile.

A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor prognosis. Current standard of care is rarely effective against late-stage pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic cancer model and characterized corresponding changes in the immune profile.

Nano-pulse stimulation induces potent immune responses, eradicating local breast cancer while reducing distant metastases.

Nano-pulse stimulation (NPS) as a developing technology has been studied for minimally invasive, nonthermal local cancer elimination for more than a decade. Here we show that a single NPS treatment results in complete regression of the poorly immunogenic, metastatic 4T1-Luc mouse mammary carcinoma. Impressively, spontaneous distant organ metastases were largely prevented, even in those animals with incomplete tumor regression.

Controllable Moderate Heating Enhances the Therapeutic Efficacy of Irreversible Electroporation for Pancreatic Cancer.

Irreversible electroporation (IRE) as a non-thermal tumor ablation technology has been studied for the treatment of pancreatic carcinoma and has shown a significant survival benefit. We discovered that moderate heating (MH) at 43 °C for 1-2 minutes significantly enhanced ex vivo IRE tumor ablation of Pan02 cells by 5.67-fold at 750 V/cm and by 1.

Thermal Assisted In Vivo Gene Electrotransfer.

Gene electrotransfer is an effective approach for delivering plasmid DNA to a variety of tissues. Delivery of molecules with electric pulses requires control of the electrical parameters to achieve effective delivery. Since discomfort or tissue damage may occur with high applied voltage, the reduction of the applied voltage while achieving the desired expression may be an important improvement.

Controlled gene delivery can enhance therapeutic outcome for cancer immune therapy for melanoma.

Effective delivery still remains a major hurdle in the development of gene based therapies. While technological advances have occurred that have improved delivery in general, there is still a need for controlled delivery in order to achieve therapeutic effects. Gene electrotransfer (GET) can be utilized to accomplish this.

Application of increased temperature from an exogenous source to enhance gene electrotransfer.

The presence of increased temperature for gene electrotransfer has largely been considered negative. Many reports have published on the lack of heat from electrotransfer conditions to demonstrate that their effects are from the electrical pulses and not from a rise in temperature. Our hypothesis was to use low levels of maintained heat from an exogenous source to aid in gene electrotransfer.

Gene electrotransfer enhanced by nanosecond pulsed electric fields.

The impact of nanosecond pulsed electric fields (nsPEFs) on gene electrotransfer has not been clearly demonstrated in previous studies. This study was conducted to evaluate the influence of nsPEFs on the delivery of plasmids encoding luciferase or green fluorescent protein and subsequent expression in HACAT keratinocyte cells. Delivery was performed using millisecond electric pulses (msEPs) with or without nsPEFs.

Loss of RAGE defense: a cause of Charcot neuroarthropathy?

Objective: This study investigated the relationship between circulating soluble receptor for advanced glycation end products (sRAGE) and parameters of bone health in patients with Charcot neuroarthropathy (CNA).

Research Design And Methods: Eighty men (aged 55.3±9.

Intramuscular injection of islet neogenesis-associated protein peptide stimulates pancreatic islet neogenesis in healthy dogs.

Objectives: Diabetes is a serious health problem. It has been proposed that islet neogenesis from pancreatic progenitor cells may restore insulin secretion in diabetic mammals. Islet neogenesis- associated protein (INGAP) stimulates islet neogenesis; therefore, we hypothesized that it would stimulate islet neogenesis in dogs.

Clinical features and morphological characterization of 10 patients with noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS).

Objective: Noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), characterized by postprandial neuroglycopaenia, negative prolonged fasts and negative perioperative localization studies for insulinoma, but positive selective arterial calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas, is a rare hypoglycaemic disorder of undetermined aetiology. We analysed the clinical, morphological and immunohistological features to further clarify the aetiology and pathogenesis of this rare disease.

Patients: Ten consecutive patients with NIPHS (nine men and one woman, aged 29-78 years) were included in the study.

Intraepidermal nerve fibers are indicators of small-fiber neuropathy in both diabetic and nondiabetic patients.

Objective: Small-fiber neuropathies may be symptomatic yet escape detection by standard tests. We hypothesized that morphologic changes in intraepidermal nerves would correlate with clinical measures of small-fiber neuropathy.

Research Design And Methods: We studied 25 diabetic and 23 nondiabetic patients with neuropathy defined by signs, symptoms, and quantitative testing and 20 control subjects.