Coordination of glioblastoma cell motility by PKCι

Background  

Glioblastoma is one of the deadliest forms of cancer, in part because of its highly invasive nature. The tumor suppressor PTEN is frequently mutated in glioblastoma and is known to contribute to the invasive phenotype. However the downstream events that promote invasion are not fully understood. PTEN loss leads to activation of the atypical protein kinase C, PKCι. We have previously shown that PKCι is required for glioblastoma cell invasion, primarily by enhancing cell motility. Here we have used time-lapse videomicroscopy to more precisely define the role of PKCι in glioblastoma.     

A βIV-spectrin/CaMKII signaling complex is essential for membrane excitability in mice

Ion channel function is fundamental to the existence of life. In metazoans, the coordinate activities of voltage-gated Na⁺ channels underlie cellular excitability and control neuronal communication, cardiac excitation-contraction coupling, and skeletal muscle function. However, despite decades of research and linkage of Na⁺ channel dysfunction with arrhythmia, epilepsy, and myotonia, little progress has been made toward understanding the fundamental processes that regulate this family of proteins. Here, we have identified β_IV-spectrin as a multifunctional regulatory platform for Na⁺ channels in mice. We found that β_IV-spectrin targeted critical structural and regulatory proteins to excitable membranes in the heart and brain. Animal models harboring mutant β_IV-spectrin alleles displayed aberrant cellular excitability and whole animal physiology. Moreover, we identified a regulatory mechanism for Na⁺ channels, via direct phosphorylation by β_IV-spectrin–targeted calcium/calmodulin-dependent kinase II (CaMKII). Collectively, our data define an unexpected but indispensable molecular platform that determines membrane excitability in the mouse heart and brain.     

In vitro chemosensitivity of head and neck cancer cell lines

Background

Systemic treatment of head and neck squamous cell carcinoma (HNSCC) includes a variety of antineoplastic drugs. However, drug-resistance interferes with the effectiveness of chemotherapy. Preclinical testing models are needed in order to develop approaches to overcome chemoresistance.

Methods

Ten human cell lines were obtained from HNSCC, including one with experimentally-induced cisplatin resistance. Inhibition of cell growth by seven chemotherapeutic agents (cisplatin, carboplatin, 5- fluorouracil, methotrexate, bleomycin, vincristin, and paclitaxel) was measured using metabolic MTT-uptake assay and correlated to clinically-achievable plasma concentrations.

Results

All drugs inhibited cell growth in a concentration-dependent manner with an IC50 comparable to that achievable in vivo. However, response curves for methotrexate were unsatisfactory and for paclitaxel, the solubilizer cremophor EL was toxic. Cross-resistance was observed between cisplatin and carboplatin.

Conclusion

Chemosensitivity of HNSCC cell lines can be determined using the MTT-uptake assay. For DNA-interfering cytostatics and vinca alkaloids this is a simple and reproducible procedure. Determined in vitro chemosensitivity serves as a baseline for further experimental approaches aiming to modulate chemoresistance in HNSCC with potential clinical significance.     

雷米普利和氯沙坦对动脉粥样硬化早期形成的影响

目的 :研究雷米普利和氯沙坦对动脉粥样硬化 (atherosclerosis,AS)早期形成的影响。方法 :将 4 4只金黄地鼠随机分为 5组 ,分别给常规饲料 (对照组 )、高脂饲料 (含 10 %椰子油和 0 .0 5 %胆固醇 )、高脂饲料加雷米普利 (2mg·kg 1)、高脂饲料加氯沙坦 (10mg·kg 1)和高脂饲料加雷米普利 (2mg·kg 1)与氯沙坦 (10mg·kg 1)处理12周 ,测定血压、血脂、AS斑块面积和肝组织中胆固醇含量的变化。结果 :数据表明雷米普利和氯沙坦不论是单独应用还是联合应用均能有效降低平均动脉压 (P <0 .0 0 1)和肝组织中胆固醇的含量 ,雷米普利能显著降低血浆中甘油三酯的水平 (P <0 .0 5 ) ,结果还显示雷米普利与氯沙坦联合应用能提升血浆中高密度脂蛋白 (P <0 .0 5 ) ,各药物处理组的AS斑块面积有不同程度降低但无统计学意义。结论 :雷米普利与氯沙坦具有一定的抑制AS形成作用 ,其机制可能与降低血压和改变脂代谢有关。