Tumor’host interaction in the optimization of paclitaxel-based combination therapies with vascular targeting compounds

Targeting of the tumor stroma, including the tumor vasculature, represents a new frontier in the treatment of malignancy. Preclinical studies and clinical experiences have established that stroma-directed novel agents must be combined with conventional therapies in order to achieve relevant therapeutic efficacy. Here we review our preclinical experience on combinations of paclitaxel with a tyrosine kinase receptor inhibitor of angiogenesis (SU6668) and a vascular disrupting agent (VDA, ZD6126), and discuss the critical factors that determine the outcome of these treatments. We also analyze the relevance of the intrinsic sensitivity of the tumor to the drugs, as well as the possibility that the two combined agents synergistically affect the vasculature or independently target the host and the tumor compartments. Finally, we discuss the need to carefully optimize scheduling and sequencing, through the use of reliable end points, in order to avoid negative pharmacological interactions and to improve the antineoplastic efficacy of paclitaxel-based combination treatments.     

The adjuvant effects of Antrodia Camphorata extracts combined with anti-tumor agents on multidrug resistant human hepatoma cells

AIM OF THE STUDY: The objectives of this study were to investigate the adjuvant anti-tumor effects of Antrodia camphorate in human hepatoma cells (C3A and PLC/PRF/5) which are resistance to most anti-tumor agents, elucidate the possible regulation pathways, and measure the tumor growth and survival rate in xenograft-nude mice after combined with anti-tumor agents. MATERIALS AND METHODS: The AC extracts were measured by using a phenol/sulfuric acid method as previously described. The in vitro cell proliferation assay of ACs and anti-tumor agents was tested on C3A and PLC/PRF/5 cell lines. The percentage of human hepatoma cells undergoing apoptosis and distributing in different phases of cell cycle were determined by Flow cytometric analysis. Western blot analysis for MDR-1 and apoptosis- related proteins. The measurements of tumor growth and survival analysis of hepatoma implanted nude mice treated with Antrodia camphorata extracts and anti-tumor agents alone or in combinations. RESULTS: We have found that Antrodia camphorata extracts, when combined with anti-tumor agents, showed adjuvant antiproliferative effects on hepatoma cells (in vitro) and on xenografted cells in tumor-implanted nude mice (in vivo), which then extended their median survival days. Furthermore, solid-state extracts of Antrodia camphorata (AC-SS) showed its adjuvant effects through the inhibition of MDR gene expressions and the pathway of COX-2- dependent inhibition of p-AKT, which ultimately resulted in the induction of apoptosis in hepatoma cells. CONCLUSIONS: In this study, we have found that Antrodia camphorata extract, when combined with anti-tumor agents, showed adjuvant antiproliferative effects on hepatoma cells (in vitro) and on xenografted cells in tumor-implanted nude mice (in vivo).     

芪月降脂片对高脂血症大鼠血脂代谢的影响

目的：观察芪月降脂片（QHT）对高脂血症大鼠血脂代谢的影响。 方法：Wistar大鼠随机分为正常对照组、高脂模型组、阳性对照组及QHT 1.75、3.50、7.00 g·kg^-1组。采用喂饲高脂饲料同时灌胃QHT,连续4周,观察QHT对大鼠高脂血症的预防作用;采用喂饲高脂饲料1周后灌胃QHT,连续3周,观察QHT对大鼠高脂血症的治疗作用。 结果：与高脂模型组比较,QHT预防和治疗方式给药均能明显降低实验性高血脂大鼠血清总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白胆固醇（LDL-C）含量、动脉硬化指数（AI）、TC/HDL-C及LDL-C/HDL-C比值（P<0.05或P<0.001）,治疗给药亦能明显提高实验性高脂血症大鼠血清高密度脂蛋白胆固醇（HDL-C）含量（P<0.05）。 结论：QHT对大鼠实验性高脂血症具有预防和治疗作用。     

Biopolymer-Based Films from Sodium Alginate and Citrus Pectin Reinforced with SiO2

Blend films based on sodium alginate (SA) and citrus pectin (P) reinforced with different concentrations of SiO₂ (0–10% w/w) were developed in this study. From the morphological (SEM) and structural (FT-IR) evaluation, it was verified that the incorporation of the reinforcing agent did not drastically modify the microstructure of the films, nor did new chemical bonds form. However, the XRD results suggested a slight reduction in the crystallinities of the blends by the incorporation of SiO₂. Among the formulations prepared, the addition of a 5% reinforcing agent was responsible for the simultaneous improvement of mechanical and barrier properties. Comparing the control sample (SA/P) with the SA/P/5.0%SiO₂ film, the tensile strength increased from 27.7 ± 3.7 to 40.6 ± 4.5 MPa, and the water-vapor transmission rate decreased from 319.8 ± 38.7 to 288.9 ± 23.5 g m⁻² day⁻¹. Therefore, SiO_2, as a reinforcing agent in SA/P blends, represents a simple and effective strategy for improving the properties of biopolymer-based films in applications, such as packaging.     

临床药师促进普外科预防性抗生素的合理使用

目的 通过临床药师对普外科预防性抗生素使用现状的调查,促进预防性抗生素的合理使用.方法 临床药师对267例普外科病人预防性使用抗生素的情况进行回顾性分析,根据不合理使用预防性抗生素的情况,提出合理使用措施并参与后续1 2 4例病人临床用药指导.结果 267例病人中预防性抗生素不合理使用率为81%,术后感染率为9.2%,提出合理措施后124例病人预防性抗生素不合理使用率为1.8%,术后感染率为1.2%(P＜0.05).结论 通过临床药师对普外科不合理使用抗生素的现况分析,提出相应措施,不合理使用情况明显下降,效果显著.     

我院抗菌药物不良反应报告相关因素分析

目的了解医院抗菌药物不良反应发生的特点及规律,为临床合理用药提供参考。方法收集医院124例抗菌药物不良反应报告,从患者情况、不良反应的临床表现、给药途径、抗菌药物种类及因果关系评价等方面进行回顾性统计分析。结果124例抗菌药物不良反应报告中,女性多于男性;以儿童和老年患者居多;引起不良反应的药物以头孢菌素类居首位,共59例,占47.58%。不良反应累及的系统或器官主要是皮肤及其附件29例,占23.39%;消化系统27例,占21.77%;严重及少见不良反应10例,占8.06%。给药途径以静脉滴注最多,共111例,占89.52%。结论加强抗菌药物分级管理,严格掌握用药指征,减少或者避免不良反应的发生。     

rhTNF-α对成骨向分化前后的人脂肪基质细胞分泌血管生成相关生长因子的影响

目的：研究在重组人肿瘤坏死因子（recombinant human tumor necrosis factor alpha,rhTNF-α）刺激下人脂肪基质细胞（human adipose tissue-derived stromal cells, hADSCs）增殖的改变及成骨向分化前后血管内皮生长因子（vascular endothelial growth factor,VEGF）、成纤维细胞生长因子2（fibroblast growth factor-2,FGF-2）和胰岛素样生长因子1（insulin-like growth factor-1,IGF-1）分泌的变化。方法：采用吸脂术获得的第4代hADSCs,以终浓度为0、1、5、10、50、100 μg/L的rhTNF-α刺激hADSCs,分别在48、72、96 h后行MTT法检测不同浓度rhTNF-α对hADSCs增殖的影响;并以该浓度梯度的rhTNF-α刺激hADSCs,24 h后收集上清,以ELISA法检测VEGF、FGF-2和IGF-1的分泌情况;在成骨向诱导的第1、3、7、14天收集细胞上清,ELISA法检测上述3种生长因子分泌的变化,收集细胞上清前24 h更换培养基,并在相应孔中加入rhTNF-α,使其终浓度为10 μg/L。所有ELISA数据均以相应培养孔的细胞数进行校正。结果：rhTNF-α能促进hADSCs的增殖,其作用表现为一定的浓度和时间依赖。相比于对照组,48 h时,10 μg/L rhTNF-α对增殖的促进作用并不明显,但96 h时则表现为促进作用（P<0.01）,而100 μg/L rhTNF-α在48 h表现为抑制作用（P<0.01）,96 h时则表现为明显的促进作用（P<0.01）。相对于对照组,rhTNF-α可以显著促进hADSCs分泌VEGF、FGF-2和IGF-1（P<0.01）;hADSCs经成骨向诱导后,上述3种生长因子的分泌有增加的趋势;不同成骨向分化阶段的hADSCs用10 μg/L rhTNF-α刺激后,在诱导第1天,rhTNF-α显著促进VEGF的分泌（P<0.01）,但对FGF-2和IGF-1的分泌无显著性影响;在诱导第3天和第7天,rhTNF-α对VEGF（P<0.01）、FGF-2（P<0.05）和IGF-1（P<0.05）的分泌均有促进作用;但在第14天则抑制VEGF（P<0.01）、FGF-2（P<0.05）和IGF（P<0.05）的分泌。结论：一定浓度的rhTNF-α对hADSCs的增殖有促进作用;hADSCs分泌VEGF、FGF-2和IGF-1具有rhTNF-α的浓度依赖;在不同成骨向分化阶段,rhTNF-α对hADSCs分泌VEGF、FGF-2和IGF-1这3种生长因子的作用不同。