阿霉素联合阿莫西林钠克拉维酸钾对人胃癌AGS细胞的作用

目的:探讨化疗联合阿莫西林钠克拉维酸钾对胃癌AGS细胞的影响.方法:应用阿莫西林钠克拉维酸钾及其分别联合阿霉素(ADM)处理AGS细胞,应用MTT、Transwell模型,流式细胞术检测细胞增殖、迁移能力及细胞凋亡.结果:阿莫西林钠克拉维酸钾可呈浓度和时间依赖性抑制胃癌AGS细胞的增殖、迁移并促其凋亡(P均<0.05).阿莫西林钠克拉维酸钾可协同化疗药物抑制胃癌AGS细胞的增殖、迁移并促其凋亡(P均<0.05).结论:阿莫西林钠克拉维酸钾可抑制胃癌AGS细胞的增殖、迁移并促其凋亡,并与阿霉素联用具有协同作用.     

表阿霉素诱导人肝癌SMMC-7721细胞凋亡的实验研究

目的 进一步探讨表阿霉素治疗原发性肝癌的作用机理。方法 应用DNA电泳、电镜、流式细胞仪分析技术，观察表阿霉素诱导人肝癌SMMC－7721细胞凋亡模式。结果 0.1μg/ml表阿霉素作用细胞12、24、36、48小时及0.1、1.0、10.0、100μg/ml表阿霉素作用细胞24小时均可出现细胞凋亡现象，其诱导凋亡效率与剂量、时间呈正相关。结论 表阿霉素可诱导人肝癌SMMC－7721细胞凋亡而发挥抗肿瘤作用。     

用DDC预处理肝癌提高阿霉素纳米粒的抗肿瘤效果

目的 通过用DDC（Diethyldithiocarbamate)预先处理耐药肿瘤细胞和荷有Walk-256肝癌模型的大鼠的方法，考察此方法对提高纳米级阿霉素碘油乳剂体内外抗肿瘤作用的可行性。方法 用MTT试验评价阿霉素及其纳米级碘油乳剂对耐药细胞及肿瘤细胞的杀灭作用，用220－250g SD大鼠建立Walk-256肝癌模型，通过肝动脉分别注入生理盐水、阿霉素、纳米级阿霉素碘油乳剂。DDC加纳米级阿霉素碘油乳剂以及DDC加阿霉素脂质体碘油乳剂，分别测定各组的肿瘤生长率和生命延长率。结果 经过DDC预处理后，阿霉素对两种阿霉素耐药肿瘤细胞SGC7901／CVR和SGC790／WT的IC50（μg.mL^-1)分别从原来的18.4降至0.74和从4．0降至0．32。除生理盐水外，各组处理后的肿瘤体积均有所下降，未用DDC处理过各组的平均肿瘤生长率远大于预先用DDC处理过的各组（P＜0．01）。而生命延长率则明显小于预先用DDC处理过的各组（P＜0．05）。结论 通过用DDC预先处理来抑制肿瘤细胞中的SOD可以提高阿霉素的抗肿瘤作用，脂质体和聚氰基丙烯酸正丁酯纳米粒作为阿霉素的释放载体，使阿霉素具有缓释性和一定的组织靶向性，延缓了肿瘤细胞中被DDC抑制的超氧化物，增强肿瘤细胞中自由基的作用，提高了疗效。     

葫芦素B和阿霉素联合应用在体内外对肝癌细胞H22的生长抑制作用

目的研究葫芦素B和阿霉素联合应用在体内外对肝癌细胞H22的生长抑制作用。方法将40只雌性昆明小鼠随机分为4组,每组10只,包括阴性对照组(生理盐水组)、阿霉素组、葫芦素B组、联合组。分别以阿霉素、葫芦素B、葫芦素B联合阿霉素处理H22细胞,培养48 h后MTT法检测细胞增殖情况。计算抑瘤率、白细胞数、胸腺指数、脾脏指数和血药浓度。结果 MTT结果显示,与阿霉素组相比,联合组对H22细胞的增殖抑制作用明显增强,联合组与阿霉素组之间、高剂量组与低剂量组之间的差异均有统计学意义(P<0.05或P<0.01)。联合组与阿霉素组相比,抑瘤率明显增强,并且联合组阿霉素在心脏中的浓度明显降低(P<0.05)。结论葫芦素B和阿霉素联合应用具有增强抗H22肝癌作用。     

漆树黄酮逆转人肝癌细胞HepG2上皮间质转化的实验研究

目的研究漆树黄酮对人肝癌细胞HepG2上皮间质转化的影响及其可能机制。方法用不同浓度的漆树黄酮(50、100、200μmol.L-1)处理HepG2细胞;MTT法检测漆树黄酮对HepG2细胞的细胞毒作用;用Transwell小室法检测漆树黄酮对HepG2细胞侵袭能力和趋化运动能力的影响,RT-PCR法检测p38MAPK、E-cadherin和vimentin mRNA表达,Western blot检测p38MAPK、E-cadherin和vimentin蛋白表达。结果漆树黄酮作用细胞24 h后能抑制HepG2细胞体外趋化运动和侵袭能力。漆树黄酮能引起HepG2细胞形态学的变化,能降低p38 MAPK和vimentin mRNA和蛋白表达,但不能改变E-Cadherin的表达。结论漆树黄酮能逆转人肝癌细胞HepG2的上皮间质转化,其抗肿瘤侵袭运动的机制可能与抑制p38MAPK的表达有关。     

NVP-AEW-541联合阿霉素诱导肝癌细胞株smmc-7721凋亡

目的 研究胰岛素样生长因子Ⅰ型受体(IGF-IR)激酶抑制剂NVP-AEW-541及阿霉素联用对肝癌细胞株smmc-7721的治疗效果.方法 NVP-AEW-541与阿霉素单独和联合应用肝癌细胞株smmc-7721后,MTT法检测细胞生长抑制率,流式细胞术检测细胞凋亡,Western blot检测p27、抗凋亡蛋白Bcl-2及促凋亡蛋白Bax的表达.结果 NVP-AEW-541和阿霉素均可诱导smmc-7721细胞凋亡.与单独使用相比,两药联用对smmc-7721细胞抑制作用有明显提高(P<0.05),细胞凋亡率增加(P<0.05),对增加Bax、p27的表达及抑制Bcl-2的表达更明显.结论 NVP-AEW-541和阿霉素均可抑制smmc-7721细胞的增殖、诱导细胞凋亡,在一定浓度范围内,呈量-效关系.     

桂皮酸体外诱导人肝癌细胞分化

目的 观察桂皮酸（CINN）对SMMC－7721细胞的诱导分化作用。方法 体外培养人肝癌细胞SMMC－7721,加入不同浓度的CINN,通过对其形态学、细胞增殖动力学、细胞生物化学行为及细胞周期分布的观察,探讨CINN对肿瘤细胞的诱导分化能力。结果 经CINN处理后,SMMC－7721细胞形态趋向良性分化,生长减速慢,集落形成率显著降低,甲胎蛋白分泌减少,FCM检测显示G0／G1期细胞增加而G2＋M期细胞减少。结论 CINN对SMMC－7721细胞有较好的诱导分化作用。     

Preparation,characterization and evaluation of liposomal doxorubicin and harmine that show synergistic activity in vitro

A combinatory therapeutic system that simultaneously targets several independent pathways is preferred for the treatment of cancer. In our study, a combinatory liposomal delivery system containing doxorubicin (Dox) and harmine (HM) was constructed by thin film dispersing method together with pH gradient method. A simple, precise and accurate spectrophotometric method for the determination of Dox and HM in liposomal formulation was established and validated. A drug HSPC ratio of 1: 20, loading time of 30 min and loading temperature of 50 °C were the optimal conditions for the preparation of drug loaded liposomes, which exhibited excellent physicochemical properties such as average particle size of ~100 nm, low polydispersity index below 0.2 and high entrapment efficiency above 93%. Sustained release of drug from liposomes at pH 7.4 showed good biological safety. The synergetic cytotoxic effect for these two drugs was evaluated in MCF-7 cells. The in vitro antitumor studies demonstrated the superior anti-proliferation activity of the liposomal Dox and HM with a combination index of 0.81, which indicated great synergistic effect and increased anti-proliferation efficiency. The experimental data suggested that combinational liposome therapy could be an effective way to develop efficient treatment of cancers.     

盐酸多柔比星联合环磷酰胺治疗乳腺癌患者的临床疗效

目的 针对乳腺癌患者采用盐酸多柔比星联合环磷酰胺治疗的疗效进行分析.方法 90例乳腺癌患者,根据化疗方式不同分为对比组和观察组,每组45例.对比组患者采取常规化疗方式(多西他赛、吡柔比星联合顺铂化疗法)进行治疗,观察组患者采取新辅助化疗方式(多西他赛、盐酸多柔比星联合环磷酰胺化疗法)进行治疗.对比两组患者近期疗效、远期...     

Self-assembled nanoparticles based on galactosylated O-carboxymethyl chitosan-graft-stearic acid conjugates for delivery of doxorubicin

A novel polymer, i.e. galactosylated O-carboxymethyl chitosan-graft-stearic acid (Gal-OCMC-g-SA) was synthesized for liver targeting delivery of doxorubicin. The chemical structure was characterized by FT-IR, ¹H NMR and elemental analysis. Gal-OCMC-g-SA could self-assemble into nanoparticles with diameter of 160 nm by probe sonication in aqueous medium and exhibited a low critical aggregation concentration of 0.047 mg/mL. The DOX-loaded Gal-OCMC-g-SA (Gal-OCMC-g-SA/DOX) self-assembled nanoparticles were almost spherical in shape with an average diameter of less than 200 nm and zeta potential of around −10 mV. In vitro release revealed that the Gal-OCMC-g-SA/DOX nanoparticles exhibited a sustained and pH-dependent drug release manner. Furthermore, the hemolysis test demonstrated the good safety of Gal-OCMC-g-SA in blood-contacting applications. These results indicated that Gal-OCMC-g-SA/DOX nanoparticles were highly potential to be applied in cancer therapy.     

The selective effect of cystathionine on doxorubicin hepatotoxicity in tumor-bearing mice

The aim of the present study was to examine the protective effect of cystathionine as a cysteine precursor on doxorubicin toxicity in the liver of Ehrlich ascites tumor (EAT)-bearing mice and in the EAT cells. Both compounds were injected intraperitoneally alone or in combination at the following doses: cystathionine at 10 mg and doxorubicin at 5 mg per kg of body weight. In the liver of EAT-bearing mice, glutathione (GSH), cysteine and sulfane sulfur levels as well as the activities of: glutathione S-transferase, gamma-glutamyl transpeptidase, rhodanese and gamma-cystathionase significantly dropped in comparison with healthy animals. Administration of cystathionine elevated GSH and cysteine levels in the livers of EAT-bearing mice and reduced lipid peroxidation. Furthermore, cystathionine increased gamma-glutamyl transpeptidase activity, thereby activating gamma-glutamyl cycle, responsible for proper glutathione metabolism in the cells. Cystationine did not influence sulfane sulfur level and rhodanese and gamma-cystathionase activity in the livers of EAT-bearing mice. It was next shown that cystathionine administered in combination with doxorubicin protected against the drug toxicity since it elevated thiol level, lowering reactive oxygen species content and suppressing lipid peroxidation. This means that, cystathionine in the liver of EAT-bearing mice can both correct harmful effects of carcinogenesis, and protect the liver from doxorubicin cytotoxicity. In contrast, in EAT cells, cystathionine lowered GSH and cysteine levels and did not alter reactive oxygen species level, lipid peroxidation, and gamma-glutamyl transpeptidase activity. All these data indicate that cystathionine action is selectively beneficial for normal cells because it corrects harmful effects induced by EAT development and protects the organism against doxorubicin cytotoxicity without impairing cytotoxicity of this drug to tumor cells.     

丙戊酸联合顺铂对体外人非小细胞肺癌细胞的增殖抑制作用

目的探讨丙戊酸（VPA）联合顺铂（DDP）对人非小细胞肺癌细胞A549、NCI．H460增殖抑制及细胞凋亡的影响,以及两药联合影响肺癌细胞增殖的机制。方法3组不同质量浓度的VPA与DDP单药及联合作用于人非小细胞肺癌细胞A549、NCI—H460,培养24、48、72h后,观察细胞数量和形态的变化,用MTF法分析药物对细胞增殖的抑制率（IR）及联合用药对细胞增殖抑制率q值,Hoechst／PI双染检测细胞凋亡的数量变化,Westernblot观察联合用药对Bcl．2、Caspase．3、Caspase．8蛋白的表达变化。结果培养48h后,各用药组细胞数目减少十分明显,其中VPA＋DDP组较单独用药组减少更为显著,其细胞形态发生较大改变;MTF法及q值计算结果显示,对A549细胞,VPA的增殖抑制作用呈现明显的时间与浓度依赖性,在高质量浓度时（300mg·L-1）与DDP具有协同作用;对NCI—H460细胞,当VPA的质量浓度≤100mg·L-1时,未显示出明显的时间与浓度依赖性,所有浓度均未显示出VPA与DDP的协同作用。VPA联合DDP可以进一步促进A549与NCI—H460的细胞凋亡,导致两细胞中凋亡因子Bcl-2水平的明显下调。联合作用对A549细胞更为明显,可能与该细胞中抑凋亡因子Bcl-2低表达及促凋亡因子Caspase-3、Caspasel8高表达有关。结论VPA能增强DDP对人非小细胞肺癌细胞的增殖抑制作用,联合作用的协同性与药物浓度及细胞类型有关,不同类型细胞对药物敏感性的差异可能与细胞自身表达的凋亡因子的含量有关。     

A phase II trial of doxorubicin and interferon alpha 2b in advanced,non-medullary thyroid cancer

Summary Background: The combination of doxorubicin and interferon alpha is supported by preclinical data. We sought to evaluate the efficacy of this combination in patients with advanced thyroid cancer. Patients and methods: Patients with locally recurrent or metastatic, radioiodine- refractory thyroid cancer, excluding medullary carcinoma, were treated with interferon alpha-2b 12 million units/m² subcutaneously on days 1–5 and doxorubicin 40 mg/m² intravenously, on day 3, every 28 days. Results: 17 patients, 15 with well differentiated and 2 with anaplastic thyroid carcinoma, were enrolled; median age was 69 years. Three patients had received radiation plus low dose doxorubicin previously. In 16 patients assessable for response, 1 patient (6%), who had follicular carcinoma, achieved a partial response and 10 patients (62.5%) stable disease as best response. Median time to progression was 5.9 months and median overall survival 26.4 months. In 14 evaluable patients, 5 (36%) had a thyroglobulin response (30% or more reduction in serum levels). Grade 3/4 neutropenia occurred in 76% of patients and neutropenic fever in 24%. Other grade 3/4 adverse events included fatigue (41%), rigors (18%), fever (6%), nausea/vomiting (29%), anorexia (29%), stomatitis (24%), vision disturbances (18%), neuropathy (18%), and hyponatremia (6%). One patient developed heart failure. Conclusions: Doxorubicin and interferon alpha was associated with considerable toxicities but modest antitumor activity in patients with advanced, non-medullary thyroid cancer.     

Chronopharmacokinetics of doxorubicin in patients with breast cancer

Summary The chronopharmacokinetics of doxorubicin (DOX) has been studied in 18 patients suffering from breast cancer. They received combined chemotherapy, including DOX (50 mg/m² as an iv bolus), given at two different times (09.00 h or 21.00 h). The two randomized courses of the protocol were given to each patient at a four week interval.The total body clearance (CL) of DOX was significantly decreased when the drug was administered at 21.00 h, resulting in a longer elimination half-life and an increase in AUC. The renal clearance of DOX did not differ at the different times of administration, and it appears that the decrease in CL was related to a change in hepatic blood flow. The volume of distribution of the drug was not changed.     

Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver,kidney and pancreas tissues of STZ-induced diabetic rats: A mechanistic study

The aim of this study was to investigate the synergistic effects of quercetin (QE) and quinic acid (QA) on a STZ-induced diabetic rat model to determine their potential role in alleviating diabetes and its associated complications. In our study design, diabetic rats were treated with single and combined doses of QE and QA for 45 days to analyse their effects on liver, kidney and pancreas tissues. The study result showed that QE and QA treated groups down-regulated hyperglycaemia and oxidative stress by up-regulating insulin and C-peptide levels. Moreover, histological observations of the liver, kidney and pancreas of diabetic rats treated with single and combined doses of QE and QA showed a significant improvement in the structural degeneration. Interestingly, the combination dose of QE and QA (50 mg/kg) exhibited maximum inhibition of the pro-apoptotic protein Bax expression and demonstrate enhancement of the anti-apoptotic protein Bcl-2 expression in the kidney tissues, suggesting a protective role in the kidneys of diabetic rats. Taken together, these results indicates the synergistic effects of QE and QA in ameliorating hyperglycaemia, hyperlipidemia and insulin resistance in diabetic rats and therefore, open a new window of research on the combinatorial therapy of flavonoids.     

多柔比星脂质体联合贝伐珠单抗治疗铂类耐药型复发性卵巢癌的临床疗效和安全性观察

目的 观察多柔比星脂质体联合贝伐珠单抗治疗铂类耐药型复发性卵巢癌患者的临床疗效及安全性。方法 选取我院2017年1月—2018年12月收治的76例铂类耐药型复发性卵巢癌患者,采用随机数字分组法分为对照组和观察组,每组38例。对照组患者给予多西他赛联合贝伐珠单抗化疗6个周期,观察组患者给予多柔比星脂质体联合贝伐珠单抗化疗6个周期。比较两组患者的临床疗效,药物不良反应,血清人附睾蛋白4(HE4)、糖类抗原125(CA125)水平变化,以及中位生存期（mOS）和中位无疾病进展生存期（mPFS）。结果 治疗后,观察组患者疾病控制率（DCR）、客观有效率（ORR）分别为76.32%、57.89%,高于对照组的52.63%、31.58%(P<0.05)。观察组患者血清HE4、CA125水平均低于对照组（P<0.05）。对照组患者恶心呕吐、白细胞减少、乏力等药物不良反应发生率高于观察组（P<0.05）,但观察组心脏毒性发生率高于对照组（P<0.05）。两组患者血小板减少、肝肾功能损伤、高血压等不良反应发生率相比较,差异无统计学意义（P>0.05）。观察组患者mOS、mP...     

In vivo synergistic anti-tumor effect of paclitaxel nanoparticles combined with radiotherapy on human cervical carcinoma

In this study, our purpose was to explore the synergistic anti-tumor effect and mechanism of paclitaxel nanoparticles (PTX-NPs) combined with radiotherapy (RT) on human cervical carcinoma (HeLa). PTX-NPs were prepared by a solid dispersion method using methoxy poly(ethylene glycol)–poly(?-caprolactone) (MPEG–PCL), which combined with RT exerted a potent and high efficient effect against cervical cancer. In vivo antitumor activity of PTX-NPs combined with RT, was estimated using nude mice carrying Hela cell xenograft tumor. The results were evaluated using microfluorine-18-deoxyglucose PET/computed tomography (¹⁸F-FDG PET/CT) and immunohistochemistry. The results showed that PTX-NPs possessed a more efficient effect than PTX when combined with RT (p?相似文献