Combination of flavone acetic acid (FAA) with adriamycin,cis-platinum and difluoromethylornithine (DFMO) in vitro against human colon cancer cells

Summary Unresectable solid tumors in the metastatic stage are quite resistant to current chemotherapy and radiation therapy regimens. Flavone acetic acid (FAA) is a novel antitumor agent which appears to work through a different mechanism than the conventional chemotherapeutic agents. In preclinical studies it has shown effectiveness against a variety of transplantable murine and human tumors and appears to be solid tumor selective. It also has non-overlapping toxicities as compared to conventional agents. We therefore investigated FAA in vitro against human colon cancer cells and explored whether its effectiveness could be enhanced in combination with other agents such as adriamycin (ADR), cis-platinum (CP) and difluoromethyornithine (DFMO) — an inhibitor of polyamine biosynthesis. Addition of FAA for 24 hours in liquid media produced dose dependent growth inhibition. Using soft agar colony assay, growth was inhibited by 58% by 3mM FAA and only 1.4% by 0.375mM FAA. The combination of FAA and cis-platinum produced synergism at the lower doses tested. The combination of FAA and adriamycin produced antagonism at all doses tested and the combination of FAA with DFMO did not produce results significantly different from DFMO alone. We conclude that enhancement of FAA activity can be achieved in combination with conventional antitumor agents, but may be drug and dose specific.     

纳米羟基磷灰石/硫酸钙复合人工骨顺铂缓释系统注射液的制备与研究

目的研制可注射α-CSH-nano-HA/PHBV-PEG顺铂释药系统,为骨转移瘤提供新型的局部药物缓释系统。方法α-CSH-nano-HA/PHBV-PEG载顺铂制成可注射用α-CSH-nano-HA/PHBV-PEG cis-platinum缓释微球,研究其结构、释药特性、可注射性以及力学性能。结果(1)第1、3、5、7天缓释微球的释药浓度分别为97.5、90.7、83.2、68.5μg/mL,第7天后趋于稳定。(2)可注射α-CSH-nano-HA/PHBV-PEG顺铂释药系统在液固比为0.7时可注射性强,与此同时缓释药系统随着液固比的增大凝固时间延长。结论α-CSH-nano-HA/PHBVPEG顺铂释药系统具有良好的注射性能和缓释作用。     

外源性IL-18基因转染联合顺铂对胶质瘤C6细胞凋亡的诱导作用

目的研究外源性IL-18基因联合顺铂对胶质瘤C6细胞的凋亡诱导作用,为胶质瘤治疗提供新的途径。方法将IL-18基因及pLXSN病毒载体导入胶质瘤C6细胞,建立C6/IL-18及C6/pLXSN细胞;C6/IL-18、C6/pLX-SN及胶质瘤C6细胞均以RPMI1640培养基培养,经0.3、3、30、60、120μg/ml顺铂作用48h后,用酶标仪在490nm波长处测吸光度值,计算细胞抑制率;以顺铂的10倍血浆峰浓度作用（3μg/ml）细胞24h后,采用吖啶橙/溴乙啶（A//EB）双荧光染色法检测细胞凋亡率。结果 C6/IL-18细胞、C6/pLXSN细胞及亲代C6细胞经120、60、30、3、0.3μg/ml顺铂作用后的抑制率依次降低,C6/IL-18细胞抑制率明显高于C6/pLXSN和C6细胞（P均〈0.05）。以30μg/ml顺铂作用后C6/IL-18细胞的凋亡率明显高于C6/pLXSN和C6细胞（P均〈0.05）。结论外源性IL-18基因联合顺铂可明显增加对胶质瘤C6细胞的抑制作用,其相关机制有待进一步探讨。     

5-fluorouracil and cis-platinum in the treatment of refractory solid tumors: A pediatric oncology group phase I — II study

Eleven patients with osteogenic sarcoma (9), Hodgkin disease (1), and mesenchymal sarcoma (1), were treated with 5-fluorouracil (5-FU) and cisplatin (DDP). Myelosuppression and vomiting of variable degrees occurred in all. No responses were seen.     

中心静脉导管闭式引流并腔内化疗治疗恶性胸腔积液100例

目的观察中心静脉导管闭式引流结合顺铂胸腔内化疗治疗恶性胸腔积液的疗效。方法100例恶性胸腔积液患者应用中心静脉导管行胸腔闭式引流,配合顺铂行胸腔内化疗。结果治疗后近期疗效:CR 38例(38%),PR45例(45%),NC17例(17%),总有效率(CR+PR)83%。结论中心静脉导管闭式引流并顺铂腔内化疗治疗恶性胸腔积液是一种安全、方便、有效的方法,值得临床推广。     

Anguidine potentiates cis-platinum in human brain tumor cells

Summary Anguidine pretreatment was previously shown to potentiate cis-platinum in Chinese hamster ovary cells by 100-fold, probably by enhancing cellular cis-platinum. uptake. Since both cis-platinum and anguidine have been reported to have clinical efficacy in human brain tumors, the present study was initiated to investigate whether anguidine's potentiation of cis-platinum was applicable to human brain tumor cells in culture. Using the colony formation assay, it was found that anguidine enhanced cis-platinum's cytotoxicity by ten-fold, producing a dose modification factor of 1.74. Alkaline elution analysis of cis-platinum-induced DNA crosslinks found that anguidine enhanced cross-linking by a factor of 1.55, 1.76, 1.63, and 1.48 at 0, 6, 24, and 48 hr, respectively, after cis-platinum treatment. This enhancement of cross-linking is evidence for anguidine increasing cis-platinum uptake. Thus, anguidine enhances cis-platinum-induced DNA cross-linking and subsequent cytotoxicity in human brain tumor cells, and may be clinically useful in combination with cis-platinum in those tumors.     

中药复合物得力生注射液可提高顺铂对肺癌PGCL3细胞株的治疗效果

Objective:To investigate the effect of Delisheng Injection(得力生注射液 DLS),a Chinese medicinal compound,DLS combined with cis-platinum(DDP),an active agent used in lung cancer chemotherapy,on a human highly metastatic giant lung carcinoma cell line PGCL3.Methods:The suspended PGCL3 cells at10~5/mL cultured in 96-well tissue culture plates were divided into 4 groups:DLS treatment group(2 μL/mL,5 μL/mL,10 μL/mL,25 μL/mL),DDP treatment group(1 μg/mL,2 μg/mL,5 μg/mL,15 μg/mL),combined DLS with DDP treatment group(DLS:DDP 2 μL/mL:1 μg/mL,5 μL/mL:2 μg/mL,10 μL/mL:5 μg/mL,25 μL/mL:15 μg/mL)and a control group.The cytotoxicity of DLS with different concentrations(2 μL/mL,5 μL/mL,10 μL/mL,25 μL/mL)on PGCL3 cells was determined by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT) assay.Effect of DLS on adhesion of PGCL-3 cells was tested by cell-matrigel adhesion assay.Chemotactic movement model of transwell camerula was used to determine the effect of DLS on invasion and migration of PGCL-3 cells.Results:Compared with the control group,DLS(2 μL/mL,5 μL/mL,10 μL/mL,25 μL/mL) could significantly decrease cell proliferation,adhesion,invasion and migration abilities(P0.05).Cell adhesion,invasion and migration abilities were significantly decreased after combination treatment of DLS:DDP(2 μL/mL:1 μg/mL,5 μL/mL:2 μg/mL,10 μL/mL:5 μg/mL,25 μL/mL:15 μg/mL) compared with DDP single-agent treatment(1 μg/mL,2 μg/mL,5 μg/mL,15 μg/mL,P0.05),respectively.Conclusions:DLS single-agent has a satisfying inhibition effect in PGCL3 cell line and DLS might enhance the inhibition effect of DDP on cancer metastasis.Our research provided a experimental basis about the treatment on highly metastatic lung caner.     

Enhanced tumor growth in experimental whole body hyperthermia

The purpose of this study was to investigate the interaction of heat and chemotherapy in experimental whole body hyperthermia (WBH). A vascular technique of extracorporeal perfusion was employed to rapidly elevate body temperature in rabbits carrying the transplantable VX-2 carcinoma. Hyperthermia (> 41°C) was achieved in a mean time of 28 minutes. Tumor-bearing rabbits receiving WBH alone exhibited poor mean survival (14 days) relative to untreated tumor-bearing animals (32 days) and the group receiving IV Cis-platinum alone (50 days) (NS, p < .05 respectively). WBH with Cis-platinum was intermediate in terms of mean survival (30 days, NS) between the WBH alone and Cis-platinum alone groups. In this experimental model we have determined WBH to be a detrimental form of cancer therapy. Its action appears to enhance tumor proliferation, resulting in rapid animal demise. In light of these findings a reevaluation of clinical WBH may be warranted.     

攻癌利水散外敷联合重组p53基因腺病毒治疗肺癌胸水30例

目的:观察攻癌利水散外敷联合重组p53基因腺病毒注射液胸腔灌注治疗对肺癌胸水的临床疗效。方法:将150例患者随机分为中药组、p53组、中药+p53组、顺铂组、空白组,每组30例。用药2疗程后观察临床疗效、毒副作用与生活质量的改变情况。结果:总有效率中药+p53组最高,与其他各组比较,差异均有统计学意义(P0.05)。白细胞下降及消化道反应情况顺铂组较明显,与其他各组比较,差异有统计学意义(P0.05);发热p53组较明显,与其他各组比较,差异有统计学意义(P0.05)。PKS评分治疗后中药+p53组升高最明显,与其他各组比较,差异有统计学意义(P0.05)。结论:攻癌利水散外敷联合重组p53基因腺病毒注射液胸腔灌注治疗肺癌胸水临床疗效显著,且不良反应小。     

体外高频热疗联合顺铂胸腔内注射治疗恶性胸腔积液的疗效观察及护理

目的 观察体外高频热疗联合顺铂胸腔内注射治疗恶性胸腔积液的疗效.方法 采用随机分组的方法,将68例患者分为治疗组(高频热疗+顺铂+地塞米松)、对照组(顺铂+地塞米松),两组治疗前均经B超测量胸腔积液的量,并定点穿刺抽液,4周后复查B超进行疗效评价.结果 治疗组的近期疗效为89.47%,对照组为63.33%,两组疗效有显著性差异(P＜0.05).不良反应:在血液学毒性及胃肠道反应方面,两组无显著性差异;热疗组胸痛的发生率相对较低,程度较轻,缓解时间较短,且治疗组无明显烧伤现象,仅2例患者皮肤轻度发红,24 h内自行消失.结论 体外高频热疗联合顺铂胸腔内注射治疗恶性胸腔积液是一种简单方便、安全可靠、不良反应少、患者易于接受且疗效满意的治疗措施,值得推荐使用.