A designer peptide against the EAG2-Kvß2 potassium channel targets the interaction of cancer cells and neurons to treat glioblastoma.

Glioblastoma (GBM) is an incurable brain cancer that lacks effective therapies. Here we show that EAG2 and Kvß2, which are predominantly expressed by GBM cells at the tumor-brain interface, physically interact to form a potassium channel complex due to a GBM-enriched Kvß2 isoform. In GBM cells, EAG2 localizes at neuron-contacting regions in a Kvß2-dependent manner. Genetic knockdown of the EAG2-Kvß2 complex decreases calcium transients of GBM cells, suppresses tumor growth and invasion and extends the survival of tumor-bearing mice. We engineered a designer peptide to disrupt EAG2-Kvß2 interaction, thereby mitigating tumor growth in patient-derived xenograft and syngeneic mouse models across GBM subtypes without overt toxicity. Neurons upregulate chemoresistant genes in GBM cells in an EAG2-Kvß2-dependent manner. The designer peptide targets neuron-associated GBM cells and possesses robust efficacy in treating temozolomide-resistant GBM. Our findings may lead to the next-generation therapeutic agent to benefit patients with GBM.

Increased Expression of Kv10.2 in the Hippocampus Attenuates Valproic Acid-Induced Autism-Like Behaviors in Rats.

The role of potassium channels provides suggestive evidence for the etiology of autism. The voltage-gated potassium channel Kv10.2 (KCNH5) is widely expressed in the brain. However, the inherent relationship between Kv10.2 and autism is still unclear. Herein, a rat valproic acid (VPA)-induced autism spectrum disorder model was established. The expression level of Kv10.2 was obviously decreased in the hippocampus of VPA rats. Kv10.2 was mainly localized in neurons. Subsequently, a recombinant lentivirus expressing Kv10.2 was used to upregulate the expression of Kv10.2 in the hippocampus of VPA-exposed rats. The results were promising as injection of the Kv10.2 lentivirus in the hippocampus relieved anxiety and stereotypical behavior, and improved the social and exploratory abilities of rats that were prenatally exposed to VPA. In addition, spectral analysis of electroencephalogram data revealed that animals exposed to VPA exhibited increased high-frequency activity compared with the control rats, and this activity recovered to a certain extent after upregulation of Kv10.2 expression by lentivirus injection. These results suggest that changes in Kv10.2 may play an important role in the etiology of autism, thus providing a promising direction for further research on autism.

Approaches targeting K(V)10.1 open a novel window for cancer diagnosis and therapy.

K(V)10.1 has recently become generally accepted as a promising cancer target, as it is ectopically expressed in the majority of solid tumors. Due to its cell-surface accessibility, K(V)10.1 has a strong potential for tumor treatment and diagnosis. Given that its mode of action is likely independent of conventional cancer pathways such as tyrosine kinases, K(V)10.1 opens a novel window for treating cancer. In this review we will give an overview of the current status of data linking K(V)10.1 to cancer, and propose techniques that could exploit K(V)10.1's properties for the management of cancer.

Symptom and quality of life results of an international randomised phase III study of adjuvant vaccination with Bec2/BCG in responding patients with limited disease small-cell lung cancer.

AIMS: This study reports the symptom and HRQOL results in which standard treatment was compared to standard therapy plus Bec2, an anti-idiotypic antibody that mimics GD3, a ganglioside antigen. METHODS: Five hundred and fifteen LD SCLC patients were randomised to receive five vaccinations of Bec2 (2.5mg)/BCG vaccine arm (VA) or an observational arm (OA) administered over a 10-week period. Survival was the primary end-point; HRQOL was a secondary end-point, assessed using the EORTC QLQ-C30/LC 13. RESULTS: There was no improvement in survival or progression-free survival in the vaccination arm. At baseline patients in both arms demonstrated significantly impaired scores on the global QOL scale, when compared to a normative population. However, HRQOL and symptom scores between the two treatment arms were not statistically different at any time point. CONCLUSION: We found no benefits to patient HRQOL by additional vaccination with Bec2/BCG to LD SCLC for patients who have been undergoing standard therapy.

Gene therapy approaches to ventricular tachyarrhythmias.

Ventricular tachycardia arising from a healed myocardial infarction scar continues to be a significant cause of morbidity and mortality. Drug therapy has been inadequate to meet this challenge, and implantable devices are limited by expense and technical problems. We have proposed the use of gene therapy for cardiac arrhythmias. In this review, we present a model of postinfarct ventricular tachycardia, a method for gene delivery to this area, and results of KCNH2-G628S gene transfer to manipulate cellular refractory properties in the arrhythmia model.