No abstract

Gastric cancer (GC) is a common disease with few effective treatment choices and poor prognosis, and has the second-highest mortality rates among all cancers worldwide. Dysregulation and/or malfunction of ion channels or aquaporins (AQPs) are common in various human cancers. Furthermore, ion channels are involved in numerous important aspects of the tumor aggressive phonotype, such as proliferation, cell cycle, apoptosis, motility, migration, and invasion. Indeed, by localizing in the plasma membrane, ion channels or AQPs can sense and respond to extracellular environment changes; thus, they play a crucial role in cell signaling and cancer progression. These findings have expanded a new area of pharmaceutical exploration for various types of cancer, including GC. The involvement of multiple ion channels, such as voltage-gated potassium and sodium channels, intracellular chloride channels, ‘transient receptor potential’ channels, and AQPs, which have been shown to facilitate the pathogenesis of other tumors, also plays a role in GC. In this review, an overview of ion channel and aquaporin expression and function in carcinogenesis of GC is presented. Studies of ion channels or AQPs will advance our understanding of the molecular genesis of GC and may identify novel and effective targets for the clinical application of GC.

No abstract

The novel synthetic psychoactive ketamine analog methoxetamine is reportedly being used for recreational purposes. As ketamine use can result in urinary dysfunction, we conducted the present study to investigate how methoxetamine affects the bladder. A cystometry investigation showed that female Sprague-Dawley rats experienced increased micturition frequency bladder dysfunction after receiving a daily intraperitoneal injection of 30 mg/kg methoxetamine or ketamine for periods of 4 or 12 weeks. Histologic examinations of rat bladder tissue revealed damaged urothelium barriers, as well as evidence of inflammatory cell infiltration and matrix deposition. The drug-treated rats showed significantly upregulated levels of pro-inflammatory cytokines such as IL-1β, IL-6, CCL-2, CXCL-1, CXCL-10, NGF, and COX-2. In addition, interstitial fibrosis was confirmed by increased levels of collagen I, collagen III, fibronectin and TGF-β. Besides direct toxic effect on human urothelial cells, methoxetaminealso induced the upregulation related cytokines. Our results indicate that long term methoxetamine treatment can induce bladder dysfunction and inflammation in rats. Methoxetamine was confirmed to produce direct toxic and pro-inflammatory effects on human urothelial cells. Methoxetamine-associated bladder impairment may be similar to ketamine-induced cystitis.