TRAIL协同多柔比星高效杀伤骨肉瘤细胞

目的:研究TRAIL与多柔比星联合 应用对骨肉瘤细胞的杀伤作用,探寻骨肉瘤临 床化疗的新方案。方法:将TRAIL与多柔比 星单独及联合应用于体外培养的骨肉瘤 OS 732细胞,采用MTT法检测细胞毒性作 用,流式细胞仪定量分析凋亡细胞所占比例, 并镜下观察凋亡细胞超微结构改变。结果:50 ng/mL的TRAIL与5μg/mL多柔比星合用 于OS 732细胞24h时后,测细胞抑制率为 85.47%,明显高于单用TRAIL(50ng/mL)时 的9.68%及单用多柔比星(5μg/mL)时的 18.41%,P<0.01。细胞超微结构观察及凋亡 率测定均显示,合用比单用有更多的骨肉瘤细 胞凋亡。结论:TRAIL与多柔比星可协同、高 效杀伤骨肉瘤细胞,这种杀伤效应是通过促进 肿瘤细胞的凋亡来实现的。     

TRAIL联合多柔比星作用于骨肉瘤的实验研究

背景与目的：肿瘤坏死因子相关的凋亡诱导配体（TNF related apoptosis inducing ligand，TRAIL）是近年发现的肿瘤坏死因子家族新成员，显著特点是它仅诱导肿瘤细胞凋亡，对正常细胞无毒性作用。TRAIL可作为骨肉瘤靶向治疗的潜在有效药物，但单独使用时已被证明作用有限。而多柔比星可对肿瘤细胞产生广泛的生化效应，为细胞周期非特异性药物，有强烈的细胞毒性作用，可嵌入DNA而抑制核酸的合成导致细胞死亡。本研究旨在探讨TRAIL联合低剂量化疗药物多柔比星对骨肉瘤MG-63细胞的凋亡诱导效应。方法：MTT法测定TRAIL和多柔比星对MG-63细胞单独及联合作用的细胞凋亡率，DNA凝胶电泳及流式细胞仪检测细胞凋亡。结果：1000ng／ml的TRAIL与4．3μmol／mL多柔比星合用于MG63细胞24h时后，测细胞抑制率为36．65％，明显高于单用TRAIL（1000ng／ml）时的21．67％及单用多柔比星（4．3μmol／ml）时的10.25％（P〈0．01）。细胞超微结构观察及凋亡率测定均显示，合用比单用有更多的骨肉瘤细胞凋亡。TRAIL联合应用多柔比星能显著增强对MG-63的杀伤、抑制增殖及诱导凋亡作用，明显高于单独应用TRAIL组或多柔比星组（P〈0．05），并且这种作用随培养时间延长及药物浓度增加而增强。结论：TRAIL是一种有望应用于临床的新型生物制剂。TRAIL与多柔比星对诱导骨肉瘤细胞凋亡具有协同作用，能高效杀灭骨肉瘤细胞。     

艾迪与多柔比星联合对骨肉瘤细胞杀伤协同作用的观察

目的:探讨中药制剂艾迪对骨肉瘤化疗的增效作用及其相关机制。方法:将艾迪与多柔比星单独及联合应用于骨肉瘤OS732细胞,MTT法检测细胞生长抑制率,流式细胞仪定量分析凋亡细胞所占比例,倒置相差显微镜及荧光显微镜下观察凋亡细胞形态改变,免疫细胞化学技术分析凋亡相关蛋白Fas表达。结果:艾迪与多柔比星对骨肉瘤细胞都有剂量依赖性杀伤作用,艾迪浓度达到25μL/mL时,细胞生长受到抑制,再增加艾迪浓度抑制率不再明显改变,但如与1μg/mL多柔比星合用将使细胞生长抑制率进一步提升,P=0.003。细胞超微结构观察及凋亡率测定结果也显示,艾迪与多柔比星联用可诱导更多骨肉瘤细胞凋亡,且联用时骨肉瘤Fas表达明显提升,P=0.005。结论:艾迪与小剂量多柔比星合用与单用多柔比星相比可更高效杀伤骨肉瘤细胞,此作用与上调Fas表达诱导骨肉瘤细胞凋亡有关。     

TRAIL与羟基喜树碱联用协同杀伤人肺腺癌A549细胞

目的：探讨羟基喜树碱与肿瘤坏死因子相关凋亡诱导配体（tumor necrosis factor-related apoptosis inducing ligand，TRAIL）联用对肺腺癌A549细胞是否具有协同杀伤作用，并对其机制进行初步研究。方法：MTT法检测细胞毒性作用，流式细胞仪检测细胞凋亡和线粒体膜电位，Western blot分析bcl-2和bcl-xl蛋白水平变化。结果：单用100ng／mL TRAIL，4、40和400μg／mL羟基喜树碱对A549细胞杀伤率分别为13．9％、3．0％、23．4％和76．7％，联合用药的抑制率分别为43．6％、52．5％和83．1%。100ng／mL TRAIL和4μg/mL羟基喜树碱有协同作用，可使细胞线粒体膜电住降低，但不影响bcl-2和bcl-xl蛋白表达。结论：TRAIL与羟基喜树碱联用对肺腺癌A549细胞有明显的协同杀伤作用，其机制可能与羟基喜树碱降低A549细胞线粒体膜电位有关。     

艾迪协同卡铂高效杀伤骨肉瘤细胞的实验研究

目的：研究中药制剂艾迪对骨肉瘤化疗的增效作用及其相关机制。方法：将艾迪与卡铂单独及联合应用于骨肉瘤OS-732细胞,用MTT法检测细胞抑制率,流式细胞仪定量分析凋亡细胞所占比例,倒置相差显微镜及荧光显微镜下观察凋亡细胞形态改变,免疫细胞化学技术分析凋亡相关蛋白Fas表达。结果：艾迪与卡铂对骨肉瘤细胞都有剂量依赖性杀伤作用,艾迪浓度达到25μl/ml时,细胞抑制率为38.47%,再增加艾迪浓度抑制率不再明显改变,但如与1μg/ml卡铂合用将使细胞抑制率进一步提升为59.53%（P〈0.01）。细胞超微结构观察及凋亡率测定也显示,艾迪与卡铂联用可诱导更多骨肉瘤细胞凋亡,且联用时骨肉瘤Fas表达明显提升（P〈0.01）。结论：艾迪与小剂量卡铂合用和单用卡铂相比,可更高效杀伤骨肉瘤细胞,此作用与上调Fas表达诱导骨肉瘤细胞凋亡有关。     

TRAIL联合三氧化二砷诱导骨肉瘤细胞凋亡的实验研究

目的：研究TRAIL和三氧化二砷共同作用于骨肉瘤OS732细胞对其产生的的杀伤作用,来探寻临床上骨肉瘤的治疗新策略。方法：选取骨肉瘤OS732细胞作为研究对象,将TRAIL及三氧化二砷分别独自或者共同作用于骨肉瘤细胞,对骨肉瘤细胞的杀伤作用通过MTT法来测定,以抑制率的形式体现出来,并在倒置显微镜、荧光显微镜下分别观察肿瘤细胞的形态改变。结果：50ng/ml的TRAIL与2μmol/L三氧化二砷共同作用于骨肉瘤细胞24小时后,肿瘤细胞抑制率为51.32%±4.71%,此作用明显强于单独应用TRAIL（50ng/ml）时的9.85%±0.97%及单独应用三氧化二砷（2μmol/L）时的20.36%±3.84%（P〈0.01）。从细胞形态结构的改变上体现出此种杀伤作用是通过诱导细胞凋亡实现的。结论：TRAIL与三氧化二砷可以协同杀伤骨肉瘤细胞,这种杀伤效应是通过促进OS732细胞的凋亡来实现的。     

康莱特联合顺铂诱导骨肉瘤细胞凋亡的实验研究

目的:研究康莱特对骨肉瘤细胞的诱导凋亡作用及其相关机制,探寻骨肉瘤的中西医结合化疗方案。方法:免疫组化及RT-PCR方法检测不同浓度康莱特作用下骨肉瘤细胞的Fas表达,并将康莱特与顺铂单独及联合应用于骨肉瘤细胞,采用MTT法检测细胞毒性作用,流式细胞仪定量分析凋亡细胞所占比例,倒置相差显微镜、荧光显微镜及电镜下观察凋亡细胞超微结构改变。结果:康莱特可上调骨肉瘤细胞的Fas表达并诱导凋亡,康莱特浓度达到10μL/mL时,细胞抑制率不再明显改变,但与1μg/mL顺铂合用将使细胞抑制率进一步提升,P=0·000。细胞超微结构观察及凋亡率测定也显示,康莱特与顺铂联用可诱导更多骨肉瘤细胞凋亡。结论:康莱特可通过上调Fas表达诱导骨肉瘤细胞凋亡,康莱特与亚毒性剂量顺铂合用可高效杀伤骨肉瘤细胞。     

蛋白酶体抑制剂联合TRAIL杀伤骨肉瘤细胞的研究

目的观察蛋白酶体抑制剂与肿瘤坏死因子相关细胞凋亡诱导配体(TRAIL)对骨肉瘤细胞株MG-63的杀伤作用。方法骨肉瘤细胞株MG-63分别经蛋白酶体抑制剂Z-LLL-CHO和(或)TRAIL作用24h,采用MTT法检测细胞毒性作用,流式细胞仪定量分析凋亡细胞所占比例,并镜下观察细胞形态学改变。结果0.5μmol/L的Z-LLL-CHO与500ng/ml的TRAIL合用于MG-63细胞24h后,细胞存活率为61.6%±1.3%,明显高于单用Z-LLL-CHO(0.5μmol/L)时的96.6%±0.2%及单用TRAIL(500ng/ml)时的89.5%±0.7%(P<0.01)。流式细胞术、电镜及荧光显微镜观察证实,协同性杀伤作用主要通过诱导细胞凋亡实现。结论蛋白酶体抑制剂能增强TRAIL杀伤骨肉瘤细胞和诱导骨肉瘤细胞的凋亡。     

生存素反义寡核苷酸促进顺铂诱导骨肉瘤细胞凋亡

目的：探讨生存素（survivin）反义寡核苷酸（antisense oligonucleotide，ASODN）对顺铂（diamminedichloroplatinum，DDP）诱导骨肉瘤细胞凋亡的促进作用。方法：通过合成靶向survivin的ASODN转染骨肉瘤OS-732细胞并与DDP联合作用，同时设空白对照组、正义（SODN）组及DDP组进行比较。采用RT—PCR、免疫细胞化学法检测各组细胞survivin mRNA和蛋白表达状态，流式细胞仪（flow cytometry，FCM）、吖啶橙／溴化乙锭（acridine orange／ethidium bromide，AO／EB）染色法检测各组细胞凋亡水平和形态，MTT法检测细胞生长抑制情况。结果：与空白对照组、SODN组及DDP组相比，ASODN转染组细胞survivin mRNA及蛋白表达明显减弱，细胞凋亡水平较空白对照组、SODN组相应提高，细胞萎缩、染色质浓缩呈典型凋亡改变，细胞生长相对受抑；上述指标在ASODN＋DDP组变化更为明显。其细胞凋亡指数（apoptotic index，AI）和细胞生长抑制率（inhibition ratio，IR，61．36％）明显高于各单“药”组（SODN组6．81％、ASODN组31．82％和DDP组41．35％）及SODN＋DDP组（45．45％），P〈0．05。结论：As0DN能够特异性封闭骨肉瘤OS-732细胞中survivin基因表达，使其功能相应爱抑，增加细胞对DDP敏感性，进而增进DDP诱导骨肉瘤细胞凋亡效应。     

TRAIL与羟基喜树碱联用协同杀伤人肺腺癌A549细胞

目的探讨羟基喜树碱与肿瘤坏死因子相关凋亡诱导配体(tumor necrosisfactor-related apoptosis inducing ligand,TRAIL)联用对肺腺癌A549细胞是否具有协同杀伤作用,并对其机制进行初步研究。方法MTT法检测细胞毒性作用,流式细胞仪检测细胞凋亡和线粒体膜电位,Western blot分析bcl-2和bcl-xl蛋白水平变化。结果单用100ng/mL TRAIL,4、40和400μg/mL羟基喜树碱对A549细胞杀伤率分别为13·9%、3·0%、23·4%和76·7%,联合用药的抑制率分别为43·6%、52·5%和83·1%。100ng/mL TRAIL和4μg/mL羟基喜树碱有协同作用,可使细胞线粒体膜电位降低,但不影响bcl-2和bcl-xl蛋白表达。结论TRAIL与羟基喜树碱联用对肺腺癌A549细胞有明显的协同杀伤作用,其机制可能与羟基喜树碱降低A549细胞线粒体膜电位有关。     

食管癌围手术期治疗的研究现状和进展

食管癌是我国常见的恶性肿瘤之一。西方国家以腺癌为主,亚洲地区则以鳞癌为主,我国食管癌中鳞癌患者约占95％。手术为食管癌的主要治疗方法,但单纯手术的效果并不尽如人意,5年生存率不足30％。为了提高手术效果,国内外很多研究探索了手术联合围手术期治疗的综合治疗模式。目前认为,在确保疗前准确分期的基础上,对于Ⅰ期及ⅡA期的患者可直接行手术治疗;对于ⅡB期及Ⅲ期的患者可行新辅助化疗或同步放化疗后进行手术。关于术后辅助治疗,目前尚缺乏有力的循证医学证据支持,但一些研究已初步证实术后辅助治疗的有效性。此外,围手术期分子靶向药物的应用及新辅助治疗疗效预测因子的研究也越来越成为研究的热点。     

不可切除及不适合手术的食管癌患者的治疗原则

由美国癌症联合会(AJCC)与国际抗癌联盟(UICC)共同制定的食管癌新的TNM分期实施以后,对食管癌的临床研究和治疗提出了新的要求,与传统的食管癌临床研究和治疗相比,更加细化.本文根据食管癌新的TNM分期要求,就不可切除及不适合手术的食管癌治疗原则作一论述.     

Challenge and opportunities in the treatment of gastric cancer

Recent developments in treatment modalities for gastric cancer have allowed the selection of a variety of treatments, and this has resulted in some confusion in daily practice. The Japan Gastric Cancer Association issued the first edition of Gastric cancer treatment guidlelines in March, 2001 to provide a common basis of understanding of the extent of disease and selection of proper treatment among doctors, patients, and their families.     

Benefit from preoperative radiotherapy in rectal cancer treatment: disease-free patients' and oncologists' preferences

Preoperative radiotherapy (PRT) in resectable rectal cancer improves local control but increases probability of faecal incontinence and sexual dysfunction. Consensus was reached in 2001 in the Netherlands on a guideline advising PRT to new patients. Purpose was to assess at what benefit oncologists and rectal cancer patients prefer PRT followed by surgery to surgery alone, and how oncologists and patients value various treatment outcomes. Sixty-six disease-free patients and 60 oncologists (surgical, radiation, medical) were interviewed. Minimally desired benefit from PRT (local control) was assessed using the Treatment Tradeoff Method. Importance of survival, local control, faecal incontinence, and sexual dysfunction in determining treatment outcome preferences was assessed using Adaptive Conjoint Analysis. The range of required benefit from PRT varied widely within participant groups. Seventeen percent of patients would choose PRT at a 0% benefit; 11% would not choose PRT for the maximum benefit of 11%. Mean minimally desired benefit excluding these two groups was 4%. For oncologists, the required benefit was 5%. Also, how strongly participants valued treatment outcomes varied widely within groups. Of the four outcomes, participants considered incontinence most often as most important. Relative treatment outcome importance differed between specialties. Patients considered sexual functioning more important than oncologists. Large differences in treatment preferences exist between individual patients and oncologists. Oncologists should adequately inform their patients about the risks and benefits of PRT, and elicit patient preferences regarding treatment outcomes.     

Clinician and cancer patient views on patient participation in treatment decision-making: a quantitative and qualitative exploration

Patient participation in treatment decision-making is being increasingly advocated, although cancer treatments are often guideline-driven. Trade-offs between benefits and side effects underlying guidelines are made by clinicians. Evidence suggests that clinicians are inaccurate at predicting patient values. The aim was to assess what role oncologists and cancer patients prefer in deciding about treatment, and how they view patient participation in treatment decision-making. Seventy disease-free cancer patients and 60 oncologists (surgical, radiation, and medical) were interviewed about their role preferences using the Control Preferences Scale (CPS) and about their views on patient participation using closed- and open-ended questions. Almost all participants preferred treatment decisions to be the outcome of a shared process. Clinicians viewed participation more often as reaching an agreement, whereas 23% of patients defined participation exclusively as being informed. Of the participants, > or = 81% thought not all patients are able to participate and > or = 74% thought clinicians are not always able to weigh the pros and cons of treatment for patients, especially not quality as compared with length of life. Clinicians seemed reluctant to share probability information on the likely impact of adjuvant treatment. Clinicians should acknowledge the legitimacy of patients' values in treatment decisions. Guidelines should recommend elicitation of patient values at specific decision points.     

原发性肝癌五种介入治疗方法的疗效比较

目的：比较几种介入治疗大肝癌方法优劣。方法：采用Seldinger技术经股动脉穿刺插管到肝动脉并注入化疗药物和栓塞剂的方法(TACE)，合并B超引导下门静脉化疗栓塞(SPVE)或B超引导下肿瘤内无水酒精注入(PEI)或结合多频治疗；对具备手术条件的患行Ⅱ期外科手术切除的综合治疗。结果：TACE，TACE SPVE，TACE PEI，TACE及Ⅱ期手术切除，TACE结合射频治疗的肿瘤缩小率≥50％，分别为30．2％，44．9％，45．2％，58．4％；其1和2年生存率，分别为36．2％，57．9％，70．9％，94．7％，96．4％和22．9％，39．5％，41．9％，67．9％。(TACE结合射频治疗的2年生存率未随访)。结论：大肝癌的综合介入治疗优于单纯TACE治疗。     

Palliative Endoscopic Therapy for Cancer Patients with Esophageal Fistula

Objective： To find an effective treatment for advanced cancer patients with esophageal fistula. Methods： From 1998 to 2006, we studied 42 patients with advanced esophageal cancer and 5 lung cancer patients with carcinomatous esophageal fistula （3 females, 44 males, aged 29-92 years）. Ten patients with both esophageal cancer stricture and fistula were first dilated under endoscope, then a memory stent with a membrane was placed in the esophageal lumen. Others were treated only with a memory stent with a membrane, three of them with a large fistula （diameter 〉1.5 cm） were treated with bio-protein glue after placement of an esophageal metal stent. Results： The fistulas were covered by a stent and the patients could eat and drink immediately. Their quality of life was improved and their survival was prolonged, 44 out of 47 patients survived for 〉3 mo. Conclusion： Placement of esophageal stent with membrane or in combination with bio-protein glue through endoscope is an effective method for treating the bronchoesophageal fistula.     

Surgical treatment of intestinal radiation injury

A review of 43 consecutive patients requiring operation for serious intestinal radiation injury was undertaken to elucidate the efficacy of surgical treatment. The most common site of radiation injury was the rectum (19 cases), followed by the small bowel (13 cases), the colon (7 cases), and the combination of these (4 cases). The overall operative mortality was 14%; morbidity, 47%; and the postoperative symptom-free period, 18 +/- 30 months. Colostomy (N = 20) carried the lowest risk of mortality, 0%, as compared with resection (N = 17) and bypass procedure (N = 6), which were accompanied by the mortalities of 24% and 33%, respectively. During the follow-up (3-13 years) 12 patients (28%) died of recurrent cancer and 9 patients (21%) of persistent radiation injury, which yielded an overall mortality of 65% after resection and 50% and 65% after bypass and colostomy procedures, respectively. Continuing radiation damage led to 15 late reoperations. Ten of these were performed after colostomy, four after resection, and one after bypass. We conclude that colostomy cannot be regarded as a preferred operative method, because it does not prevent the progression of radiation injury and because it is, for this reason, associated with a higher late-complication rate. A more radical surgery is recommended but with the limitation that the operative method must be adapted to the operative finding.