Changes of the electrical charges across the surface cell membrane are absolutely necessary to maintain cellular homeostasis in physiological as well as in pathological conditions. The opening of ion channels alter the charge distribution across the surface membrane as they allow the diffusion of ions such as K+, Ca++, Cl−, Na+. Traditionally, voltage-gated ion channels (VGIC) are known to play fundamental roles in controlling rapid bioelectrical signaling including action potential and/or contraction. However, several investigations have revealed that these classes of proteins can also contribute significantly to cell mitotic biochemical signaling, cell cycle progression, as well as cell volume regulation. All these functions are critically important for cancer cell proliferation. Interestingly, a variety of distinct VGICs are expressed in different cancer cell types, including metastasis but not in the tissues from which these tumors were generated. Given the increasing evidence suggesting that VGIC play a major role in cancer cell biology, in this review we discuss the role of distinct VGIC in cancer cell proliferation and possible therapeutic potential of VIGC pharmacological manipulation.

Endocrine disrupting chemicals can potentially alter the reproductive physiology of fishes. To test this hypothesis, serum was collected from common carp (Cyprinus carpio) at five riverine locations in Minnesota. Male fish collected from an effluent channel below the St. Paul metropolitan sewage treatment plant had significantly elevated serum egg protein (vitellogenin) concentrations and significantly decreased serum testosterone concentrations compared to male carp collected from the St. Croix River, classified as a National Wild and Scenic River. Carp collected from the Minnesota River, which receives significant agricultural runoff, also exhibited depressed serum testosterone concentrations, but no serum vitellogenin was apparent. These data suggest that North American rivers are receiving estrogenic chemicals that are biologically active, as has been reported in Great Britain.ImagesFigure 1.Figure 2. AFigure 2. B

While poorly soluble drugs such as corticosteroids sustain drug delivery in the vitreous humor by virtue of slow dissolution, macromolecules such as antibodies and their fragments sustain their levels due to their slow clearance. However, currently there are no approaches to sustain the delivery of well water soluble small molecule drugs in the vitreous. In this study we optimized a PLA microparticle formulation for sustained intravitreal delivery of TG-0054, a well water soluble anti-angiogenic drug that is of potential value in treating choroid neovascularization. After determining the influence of process parameters on particle size and drug loading, spherical microparticles syringeable through a 27 G needle, with a mean diameter of 7.6 μm, 10% w/w TG-0054 loading, sustained in vitro drug release for at least 6 months, and low residual organic solvent content (~ 1 ppb/mg) were prepared. Microparticles as well as drug solution were assessed for their in vivo drug delivery over 3 months following intravitreal injection in New Zealand white rabbits. Drug levels in the microparticle dosed eyes at 3 months were 43.7 ± 16.2, 243 ± 42.6, 62.8 ± 22.6 μg/g vitreous, retina, and choroid-RPE, respectively, and similar to levels at one month. Intravitreal injection of plain drug solution resulted in significantly lower amounts of drug in the dosed eye, with the levels being 0.8 ± 0.5, 2.7 ± 2.8, and 4.9± 4.2 μg/g in vitreous, retina, and choroid-RPE, respectively, at one month, with no detectable drug at three months. Although surface degradation was evident, microparticles maintained their spherical structure during the 6 months in vitro study and the 3 months in vivo study, with the vitreal particle retention at 1 and 3 months being 60% and 27%, respectively. Thus, PLA microparticles capable of sustaining retinal and choroidal delivery of TG-0054 for three to six months were developed.

SAR 1118 ophthalmic drops administered thrice daily deliver therapeutic levels of SAR 1118 in the retina and can alleviate the retinal complications associated with diabetes.

Potassium ion (K+) channels have been recently found to play a critical role in cancer biology. Despite that pharmacologic manipulation of ion channels is recognized as an important therapeutic approach, very little is known about the effects of targeting of K+ channels in cancer. In this study, we demonstrate that use of the Kv11.1 K+ channel activator NS1643 inhibits tumor growth in an in vivo model of breast cancer.Tumors exposed to NS1643 had reduced levels of proliferation markers, high expression levels of senescence markers, increased production of ROS and DNA damage compared to tumors of untreated mice. Importantly, mice treated with NS1643 did not exhibit significant cardiac dysfunction. In conclusion, pharmacological stimulation of Kv11.1 activity produced arrested TNBC-derived tumor growth by generating DNA damage and senescence without significant side effects. We propose that use of Kv11.1 channels activators could be considered as a possible pharmacological strategy against breast tumors.