Cancer on motors: How kinesins drive prostate cancer progression?

Prostate cancer causes numerous male deaths annually. Although great progress has been made in the diagnosis and treatment of prostate cancer during the past several decades, much about this disease remains unknown, especially its pathobiology. The kinesin superfamily is a pivotal group of motor proteins, that contains a microtubule-based motor domain and features an adenosine triphosphatase activity and motility characteristics. Large-scale sequencing analyses based on clinical samples and animal models have shown that several members of the kinesin family are dysregulated in prostate cancer. Abnormal expression of kinesins could be linked to uncontrolled cell growth, inhibited apoptosis and increased metastasis ability. Additionally, kinesins may be implicated in chemotherapy resistance and escape immunologic cytotoxicity, which creates a barrier to cancer treatment. Here we cover the recent advances in understanding how kinesins may drive prostate cancer progression and how targeting their function may be a therapeutic strategy. A better understanding of kinesins in prostate cancer tumorigenesis may be pivotal for improving disease outcomes in prostate cancer patients.

Descending Neurogenic Evoked Potentials Monitoring Is an Effective Alternative in Spinal Deformity Surgery Under Inhaled Anesthesia.

BACKGROUND: To evaluate the reliability of descending neurogenic evoked potentials (DNEP) monitoring in spinal deformity surgery under inhaled anesthesia. METHODS: A total of 180 consecutive patients who underwent spinal deformity surgery in our scoliosis center from July 2014 to August 2016 were reviewed. Intraoperative monitoring including somatosensory evoked potentials (SEP), motor evoked potentials (MEP), and DNEP was conducted routinely throughout operation. Patients were divided into 2 groups according to anesthesia methods: group A (n = 72, inhaled anesthesia, SEP/DNEP) and group B (n = 108, total intravenous anesthesia, SEP/MEP/DNEP). Intraoperative monitoring data were collected and analyzed. RESULTS: Positive alerts were observed in 26 patients (14.5%), of whom 18 (10%) were confirmed as true-positive events in the study population. No false-negative events were recorded. In group A, the sensitivity and specificity of SEP and DNEP were 100% and 93.8% and 100% and 98.5%, respectively. For group B, the sensitivity and specificity of SEP/MEP and DNEP were 100% and 95.9% and 100% and 98%, respectively. CONCLUSIONS: DNEP monitoring seemed to be effective for the detection and prevention of iatrogenic neurologic deficits during spinal deformity surgery. This study indicates that DNEP was an effective alternative in spinal deformity surgery under inhaled anesthesia.

Synthesis and Mechanism of Co2+/Sr2+ Codoped Magnetic Lanthanum Cuprate with Excellent Corrosion Resistance.

The special structure of perovskite-like compounds allows the existence of some open spaces in the crystals that play an important role in their crystal function enhancement and can accommodate active oxygen, which helps to solve some problems in the field of corrosion prevention. The magnetic lanthanum cuprate was obtained through the doping of Co2+ and Sr2+, and compared with La2CuO4 and epoxy resin, its corrosion resistance was improved by 215.2 and 566.7%, respectively. The micromagnetic field in the crystal interfered with the state of motion of the electrons and prolonged their transport path. High concentration doping and substitution of unequal states led to the formation of oxygen vacancy defects, which could trap active oxygen molecules and inhibit cathodic corrosion reactions. The unique alternating interlayer structure of perovskite-like compounds was conducive to the release of Cu2+, thus forming a more stable passivator on the surface of the coating. La1.96Sr0.04Cu0.98Co0.02O4 had both magnetic properties and structural advantages, which enhanced the shielding property of epoxy resin and expanded the application of perovskite-like compounds in the field of corrosion prevention.

TRPC5 mediates TMZ resistance in TMZ-resistant glioblastoma cells via NFATc3-P-gp pathway.

P-glycoprotein (P-gp) acts as a pump to transport cytotoxic drugs out of cells and is upregulated in cancer cells. Suppressing the expression of P-gp is an effective strategy to overcome multidrug resistance in cancer chemotherapy. Temozolomide (TMZ) is the recommended drug for the standard treatment of patients with glioblastoma, but its clinical application is restricted due to drug resistance. Transient receptor potential channel-5 (TRPC5), a Ca2+-permeable channel, has been attributed to a different drug resistance mechanism except DNA repair system; therefore, we aimed to elucidate the mechanism regarding the role of TRPC5 in TMZ resistance. TRPC5 and P-glycoprotein (P-gp) are upregulated in TMZ-resistant glioblastoma cell lines. The downregulation of TRPC5 inhibited P-gp expression and led to a significant reversal of TMZ resistance in TMZ-resistant cell lines. TRPC5-siRNA restricted the growth of tumour xenografts in an athymic nude mouse model of TMZ-resistant cells. In specimens from patients with recurrent glioblastoma, TRPC5 was found to be highly expressed, accompanied by the upregulation of P-gp expression. The nuclear factor of activated T cell isoform c3 (NFATc3), which acts as a transcriptional factor, bridges TRPC5 activity to P-gp induction. In conclusion, these results demonstrate the functional role of the TRPC5-NFATc3-P-gp signalling pathway in TMZ resistance in glioblastoma cells.