Protein Kinase C as a Therapeutic Target in Non-Small Cell Lung Cancer

Driver-directed therapeutics have revolutionized cancer treatment, presenting similar or better efficacy compared to traditional chemotherapy and substantially improving quality of life. Despite significant advances, targeted therapy is greatly limited by resistance acquisition, which emerges in nearly all patients receiving treatment. As a result, identifying the molecular modulators of resistance is of great interest. Recent work has implicated protein kinase C (PKC) isozymes as mediators of drug resistance in non-small cell lung cancer (NSCLC). Importantly, previous findings on PKC have implicated this family of enzymes in both tumor-promotive and tumor-suppressive biology in various tissues. Here, we review the biological role of PKC isozymes in NSCLC through extensive analysis of cell-line-based studies to better understand the rationale for PKC inhibition. PKC isoforms α, ε, η, ι, ζ upregulation has been reported in lung cancer, and overexpression correlates with worse prognosis in NSCLC patients. Most importantly, PKC isozymes have been established as mediators of resistance to tyrosine kinase inhibitors in NSCLC. Unfortunately, however, PKC-directed therapeutics have yielded unsatisfactory results, likely due to a lack of specific evaluation for PKC. To achieve satisfactory results in clinical trials, predictive biomarkers of PKC activity must be established and screened for prior to patient enrollment. Furthermore, tandem inhibition of PKC and molecular drivers may be a potential therapeutic strategy to prevent the emergence of resistance in NSCLC.     

基于群体递增学习算法的癌症化学疗法优化技术研究

探索分布估计算法中最频繁用于解决现实生活中优化问题的基于群体递增学习算法在优化癌症化疗中的应用能力，并与遗传算法作相应比较。实验表明基于群体递增学习（PBIL）算法的搜寻速度以及搜寻到的可行解质量均优于遗传算法。     

Distraction intervention for preschoolers undergoing intramuscular injections and subcutaneous port access.

This study evaluated a distraction intervention designed to reduce the distress of preschool children undergoing repeated chemotherapy injections. Twenty-nine children aged 2-5 years were randomly assigned either to distraction by a developmentally appropriate electronic toy or to a wait-list control. Children who received the distraction intervention demonstrated lower overt behavioral distress and were rated by parents and nurses as less anxious than children in the control condition. The improvements were maintained over the 8-week intervention. The results suggest that a developmentally appropriate, multisensory, variable-distracting activity that requires active cognitive processing and active motor responses may be a viable cost-effective alternative to more time-intensive parent-training programs for preschool-age children. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

64层CT灌注成像评价宫颈癌化疗的疗效研究

目的探讨CT灌注成像在中晚期宫颈癌化疗中的应用价值。方法选择宫颈癌Ⅱb期以上的病例56例,化疗前行64层CT灌注扫描,记录血流量（BF）、血容量（BV）、平均通过时间（MTT）、表面通透性（PS）等参数值,并测算肿瘤大小,给予2个疗程TP方案化疗后3周行CT灌注扫描再测算宫颈癌灶大小,评价疗效。结果BV值及PS值在完全缓解（CR）、部分缓解（PR）、病变进展（PD）、病变稳定（SD）患者间的差异有统计学意义（均P〈0．05）,化疗有效患者的BV值及PS值相对较高;而BF值与MTT值在不同疗效患者间的差异无统计学意义（均P〉0．05）。结论化疗前通过CT灌注成像可测量出肿瘤的BV和PS值,从而为指导中晚期宫颈癌的治疗提供依据。     

N-Heterocyclic Carbenes and Their Metal Complexes Based on Histidine and Histamine Derivatives of Bacteriopurpurinimide for the Combined Chemo- and Photodynamic Therapy of Cancer

Photodynamic therapy (PDT) is currently regarded as a promising method for the treatment of oncological diseases. However, it involves a number of limitations related to the specific features of the method and the specific characteristics of photosensitizer molecules, including tumor hypoxia, small depth of light penetration into the tumor tissue, and low accumulation sensitivity. These drawbacks can be overcome by combining PDT with other treatment methods, for example, chemotherapy. In this work, we were the first to obtain agents that contain bacteriopurpurinimide as a photodynamic subunit and complexes of gold(I) that implement the chemotherapy effect. To bind the latter agents, N-heterocyclic carbenes (NHC) based on histidine and histamine were obtained. We considered alternative techniques for synthesizing the target conjugates and selected an optimal one that enabled the production of preparative amounts for biological assays. In vitro studies showed that all the compounds obtained exhibited high photoinduced activity. The C-donor Au(I) complexes exhibited the maximum specific activity at longer incubation times compared to the other derivatives, both under exposure to light and without irradiation. In in vivo studies, the presence of histamine in the NHC-derivative of dipropoxy-BPI (7b) had no significant effect on its antitumor action, whereas the Au(I) metal complex of histamine NHC-derivative with BPI (8b) resulted in enhanced antitumor activity and in an increased number of remissions after photodynamic treatment.     

Phytochemical Targeting of Mitochondria for Breast Cancer Chemoprevention,Therapy, and Sensitization

Breast cancer is a common and deadly disease that causes tremendous physical, emotional, and financial burden on patients and society. Early-stage breast cancer and less aggressive subtypes have promising prognosis for patients, but in aggressive subtypes, and as cancers progress, treatment options and responses diminish, dramatically decreasing survival. Plants are nutritionally rich and biologically diverse organisms containing thousands of metabolites, some of which have chemopreventive, therapeutic, and sensitizing properties, providing a rich source for drug discovery. In this study we review the current landscape of breast cancer with a central focus on the potential role of phytochemicals for treatment, management, and disease prevention. We discuss the relevance of phytochemical targeting of mitochondria for improved anti-breast cancer efficacy. We highlight current applications of phytochemicals and derivative structures that display anti-cancer properties and modulate cancer mitochondria, while describing future applicability and identifying areas of promise.     

博宁联合化疗治疗骨转移癌的疗效分析

目的 :分析单纯化疗与博守联合化疗对实体瘤骨转移引起疼痛治疗的效果。方法 :42例病人随机分为单纯化疗组和化疗联合博宁组 ,对疼痛缓解程度和活动能力改善等进行对照研究。结果 :化疗联合应用博宁组疼痛缓解率及肿瘤变化方面明显优于单纯联合化疗组 (P <0 .0 5 ) ,而在活动能力改善方面则无明显差别。结论 :博宁联合化疗治疗骨转移癌引起的疼痛效果优于单纯联合化疗