Liposome accumulation in irradiated tumors display important tumor and dose dependent differences

Radiation therapy may affect several important parameters in the tumor microenvironment and thereby influence the accumulation of liposomes by the enhanced permeability and retention (EPR)-effect. Here we investigate the effect of single dose radiation therapy on liposome tumor accumulation by PET/CT imaging using radiolabeled liposomes. Head and neck cancer xenografts (FaDu) and syngenic colorectal (CT26) cancer models were investigated. Radiotherapy displayed opposite effects in the two models. FaDu tumors displayed increased mean accumulation of liposomes for radiation doses up to 10 Gy, whereas CT26 tumors displayed a tendency for decreased accumulation. Tumor hypoxia was found negatively correlated to microregional distribution of liposomes. However, liposome distribution in relation to hypoxia was improved at lower radiation doses. The study reveals that the heterogeneity in liposome tumor accumulation between tumors and different radiation protocols are important factors that need to be taken into consideration to achieve optimal effect of liposome based radio-sensitizer therapy.     

The taccalonolides, novel microtubule stabilizers, and γ-radiation have additive effects on cellular viability

The taccalonolides are novel antimitotic microtubule stabilizers that have a unique mechanism of action independent of a direct interaction with tubulin. Cytotoxicity and clonogenic assays show that taccalonolide A and radiation act in an additive manner to cause cell death. The taxanes and epothilones have utility when combined with radiotherapy and these findings further suggest the additive effects of microtubule targeting agents with radiation on cellular proliferation are independent of direct tubulin binding and are instead a result of the downstream effects of these agents. These studies suggest that diverse antimitotic agents, including the taccalonolides, may have utility in chemoradiotherapy.     

Anticancer and radio-sensitizing evaluation of some new thiazolopyrane and thiazolopyranopyrimidine derivatives bearing a sulfonamide moiety

Recently, it has been reported that compounds bearing a sulfonamide moiety posses many types of biological activities, including anticancer activity. There are a variety of mechanisms for their anticancer activity, and the most prominent mechanism is the inhibition of carbonic anhydrase (CA) isozymes. The present work reports the synthesis of some new thiazolo[4,5-b]pyrane, thiazolo[4,5-b]pyrano[2,3-d]pyrimidine derivatives bearing a sulfonamide moiety. The design of the structures of these compounds complies with the general pharmacophoric requirements for CA inhibiting anticancer drugs. The newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Most of the screened compounds showed interesting cytotoxic activities compared to doxorubicin as a reference drug. Compounds 5, 6, 10 and 12 (IC₅₀ values 39.4 μM, 41.6 μM, 35.72 μM and 34.64 μM, respectively) exhibited higher cytotoxic activities than the reference drug doxorubicin (IC₅₀ = 71.8 μM). Additionally, the previously mentioned compounds were evaluated again for their ability to enhance the cell killing effect of γ-radiation.     

放射或放射联合泰素对鼻咽癌细胞p57kip2蛋白表达的影响

目的　研究放射或放射联合泰素对鼻咽癌细胞抑癌基因p5 7kip2 蛋白表达的影响。方法　采用免疫组织化学法和WesternBlot法检测鼻咽癌细胞照射前后p5 7kip2 蛋白表达情况。结果p5 7kip2 蛋白在鼻咽癌细胞中弱阳性表达 ,单纯照射组和照射联合泰素组可见p5 7kip2 蛋白在照射后随吸收剂量增加和时间延长其表达均上调 (P <0 0 1) ,照射联合泰素组的p5 7kip2 蛋白表达比单纯照射组明显增强 (P <0 0 1)。结论　放射或放射联合泰素对鼻咽癌细胞抑癌基因p5 7kip2 蛋白表达有明显的增强作用