加替沙星注射液治疗肺癌患者呼吸道感染临床评价

评价加替沙星注射液治疗肺癌患者呼吸道感染临床疗效和药物不良反应。回顾性分析2007年1-12月非随机选择45例肺癌患者医院外获得性呼吸道感染入院治疗的临床资料进行统计分析。应用加替沙星组与应用注射用头孢哌酮钠／舒巴坦组治疗呼吸道感染的总有效率分别为92．31％和94．74％（P〉0．05）;用药3d后咳嗽咳痰、发热、湿哆音、血象好转率分别为84．62％、95．45％、85．71％、88．OO％和57．89％、71．43％、64．29％、82．35％（P〈0．05）。不良反应发生率分别11．54％和10．53％（P〉0．05）。加替沙星治疗肺癌患者呼吸道感染疗效好,见效快,是较理想的药物。     

Methods for site-specific drug conjugation to antibodies

Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over traditional chemotherapy. Drugs and linkers have been the current focus of ADC development, in addition to antibody and target selection. Recently, however, the importance of conjugate homogeneity has been realized. The current methods for drug attachment lead to a heterogeneous mixture, and some populations of that mixture have poor in vivo performance. New methods for site-specific drug attachment lead to more homogeneous conjugates and allow control of the site of drug attachment. These subtle improvements can have profound effects on in vivo efficacy and therapeutic index. This review examines current methods for site-specific drug conjugation to antibodies, and compares in vivo results with their non-specifically conjugated counterparts. The apparent improvement in pharmacokinetics and the reduced off target toxicity warrant further development of this site-specific modification approach for future ADC development.     

靶向吲哚菁绿纳米探针介导的光声治疗

光声治疗是一种利用纳米材料的光声效应选择性破坏癌细胞的方法。本研究采用叶酸作为肿瘤靶向分子,以聚乙二醇包裹吲哚菁绿形成纳米粒子(ICG-PL-PEG-FA),利用此纳米粒子在近红外区的光吸收特性,开展光声治疗研究。实验结果表明,这种叶酸标记的纳米探针对高表达叶酸的EMT6细胞具有高靶向选择性和靶向光杀伤性。这种基于包含吲哚菁绿纳米探针的光声治疗将有潜力发展为一种安全,高效的癌症治疗技术。     

Morusin induces apoptosis and suppresses NF-kappaB activity in human colorectal cancer HT-29 cells

Morusin is a pure compound isolated from root bark of Morusaustralis (Moraceae). In this study, we demonstrated that morusin significantly inhibited the growth and clonogenicity of human colorectal cancer HT-29 cells. Apoptosis induced by morusin was characterized by accumulation of cells at the sub-G₁ phase, fragmentation of DNA, and condensation of chromatin. Morusin also inhibited the phosphorylation of IKK-α, IKK-β and IκB-α, increased expression of IκB-α, and suppressed nuclear translocation of NF-κB and its DNA binding activity. Dephosphorylation of NF-κB upstream regulators PI3K, Akt and PDK1 was also displayed. In addition, activation of caspase-8, change of mitochondrial membrane potential, release of cytochrome c and Smac/DIABLO, and activation of caspase-9 and -3 were observed at the early time point. Downregulation in the expression of Ku70 and XIAP was exhibited afterward. Caspase-8 or wide-ranging caspase inhibitor suppressed morusin-induced apoptosis. Therefore, the antitumor mechanism of morusin in HT-29 cells may be via activation of caspases and inhibition of NF-κB.     

Circulating tumor microemboli: Progress in molecular understanding and enrichment technologies

Circulating tumor cells (CTCs) and their clusters, also known as circulating tumor microemboli (CTM), have emerged as valuable tool that can provide mechanistic insights into the tumor heterogeneity, clonal evolution, and stochastic events within the metastatic cascade. However, recent investigations have hinted that CTM may not be mere aggregates of tumor cells but cells comprising CTM exhibit distinct phenotypic and molecular characteristics in comparison to single CTCs. Moreover, in many cases CTM demonstrated higher metastatic potential and resistance to apoptosis as compared to their single cell counterparts. Thus, their evaluation and enumeration may provide a new dimension to our understanding of cancer biology and metastatic cancer spread as well as offer novel theranostic biomarkers. Most of the existing technologies for isolation of hematogenous tumor cells largely favor single CTCs, hence there is a need to devise new approaches, or re-configure the existing ones, for specific and efficient CTM isolation. Here we review existing knowledge and insights on CTM biology. Furthermore, a critical commentary on current and emerging trends in CTM enrichment and characterization along with recently developed ex-vivo CTC expansion methodologies is presented with the aim to facilitate researchers to identify further avenues of research and development.     

KIF14 promotes tumor progression and metastasis and is an independent predictor of poor prognosis in human gastric cancer

The kinesin family member 14 (KIF14) is a potential oncogene and is involved in the metastasis of various cancers. Nevertheless, its function in gastric cancer (GC) remains poorly defined. The expression of KIF14 was examined in GC cell lines and a clinical cohort of GC specimens by qPCR, western blotting and immunohistochemistry (IHC) staining. The relationship between KIF14 expression and the clinicopathological features was analyzed. The effect of KIF14 on cell proliferation, colony formation, invasion and migration were investigated in vitro and in vivo. The expression of KIF14 was significantly increased in the GC tissues and cell lines. High KIF14 expression was associated with tumor stage, tumor-node-metastasis (TNM) stage and metastasis. KIF14 was an independent prognostic factor for the overall survival of GC, and a higher expression of KIF14 predicted a poorer survival. KIF14 silencing resulted in attenuated proliferation, invasion and migration in human gastric cancer cells, whereas KIF14 ectopic expression facilitated these biological abilities. Notably, the depressed expression of KIF14 inhibited Akt phosphorylation, while overexpressed KIF14 augmented Akt phosphorylation. Additionally, there was a significant correlation between the expression of KIF14 and p?Akt in GC tissues. Importantly, the proliferation, invasion and migration of the GC cells, which was promoted by KIF14 overexpression, was abolished by the Akt inhibitor MK-2206, while Akt overexpression greatly rescued the effects induced by KIF14 knockdown. Our findings are the first to demonstrate that KIF14 is overexpressed in GC, is correlated with poor prognosis and plays a crucial role in the progression and metastasis of GC.