食管鳞癌细胞分化状态对内源性光敏剂PpIX产量的影响及对PDT的应答

目的:研究食管癌细胞的分化状态对ALA产生的内源性光敏剂PpIX累积水平的影响,及对PDT的应答敏感程度.方法:以高分化食管鳞癌细胞KYSE-450和低分化食管鳞癌细胞KYSE-70为研究对象,利用荧光分光光度法测定不同浓度ALA处理后细胞内PpIX的浓度;分别使用不同剂量的红光和蓝光对细胞进行照射处理,MTS法测定PDT对细胞的光毒毒性;TdT-流式细胞法测定PDT诱导的凋亡水平,并观察凋亡细胞的胞核形态.结果:高分化KYSE-450细胞比低分化KYSE-70细胞具有更强的PpIX合成或累积水平,两者PpIX绝对浓度值在高于0.5mmol/LALA时差异显著(315.2±88.3vs156.9±79.2,P<0.05);虽然高分化细胞PpIX产量高于低分化细胞,但无论是红光PDT还是蓝光PDT,其敏感性均明显差于低分化细胞,光剂量为3.6J/cm2(红光)和0.16J/cm2(蓝光)时,两者细胞存活率有极显著差异(88.0±7.4vs25.2±4.9,红光;97.4±7.3vs40.8±4.2,蓝光;P<0.01);KYSE-450凋亡率(12.5%)亦低于KYSE-70(23.2%),细胞主要以坏死方式为主.结论:食管鳞癌细胞的分化影响了内源性光敏剂PpIX的细胞内水平;PDT效应并不单纯依赖于细胞内的光敏剂含量,细胞的生物学特征如分化状态也影响了PDT的效果;高分化细胞部分通过抑制凋亡抵制了PDT作用.     

食管鳞癌细胞KYSE-70的分化诱导对光动力学应答敏感性的抑制

目的:研究全反式维甲酸(ATRA)对低分化食管鳞癌细胞系KYSE-70的分化诱导作用及对光动力学疗法(photodynamic therapy,PDT)的应答敏感程度.方法:以高分化食管鳞癌细胞KYSE-450和低分化食管鳞癌细胞KYSE-70为研究对象,用1μmol/LATRA为诱导剂,诱导KYSE-70细胞从低分化状态向高分化状态分化,通过细胞形态学、增殖实验来验证;细胞以1mmol/LALA处理,不同剂量的450nm蓝光照射,MTT法测定PDT对细胞的光毒毒性;流式细胞法测定PDT诱导的凋亡水平,Hoechst33342染色后观察凋亡细胞的胞核形态.结果:经ATRA处理后,诱导组与对照组相比,细胞变扁平、体积增大、胞质密度减低、核变大、核密度亦减低、细胞生长缓慢.高分化KYSE-450、分化诱导后的KYSE-70细胞和未诱导KYSE-70细胞用ALA处理后进行蓝光PDT,MTT结果显示高分化KYSE-450和分化诱导后KYSE-70的细胞存活率明显高于未诱导细胞,而高分化KYSE-450细胞敏感性略微低于分化诱导后的KYSE-70细胞.当光剂量为225mJ/cm2时,诱导前后细胞存活率分别为36.23%...     

光动力疗法治疗银屑病的机制及应用进展

银屑病是一种免疫介导的慢性、复发性、炎症性疾病,其发病机制与多种免疫细胞、炎症细胞因子及炎症通路相关.光动力疗法(PDT)近年来开始应用于银屑病的治疗,其作用机制可能与免疫调节相关.目前应用局部和系统性5-氨基酮戊酸介导的PDT治疗慢性斑块型银屑病、甲银屑病,尝试应用多种新型光敏剂介导PDT治疗银屑病.但多项临床研究的...     

光动力疗法结合电离辐射联合治疗老年Bowen病的疗效

目的 观察联合应用5-氨基酮戊酸光动力疗法(ALA-PDT)与放射疗法(RT)治疗老年Bowen病(BD)的疗效.方法 随机选取4例平均年龄为69.5岁的老年BD患者,在患处涂布20％ ALA霜剂避光3～4h后选用630 nm的ALA-PDT治疗仪照射约30 min,剂量为50 J/cm2,30 min后,用激光仪发射3 Gy的电子束辐射.每2～3d重复治疗1次,通过临床常规检查和组织学检验评价治疗结果.结果 4例老年BD患者皮损获得完全缓解,平均21个月的随访期内无复发发生.结论 对老年BD采用ALA-PDT和RT联合治疗效果得到显著提升,副作用小,无瘢痕形成,复发率低.     

自凝刀射频联合艾拉光动力治疗肛管内巨大或多发性尖锐湿疣的疗效观察

目的自凝刀射频联合5-氨基酮戊酸光动力（ALA—PDT）治疗肛管内巨大或多发性尖锐湿疣（CA）的疗效观察。方法采用BBT妇科多功能治疗仪去除肛管内巨大或多发的CA后,联合艾拉光动力（ALA—PDT）治疗并定期随访。结果25例病人经治疗后全部痊愈,随访12个月均未复发。结论自凝刀射频联合艾拉光动力治疗肛管内巨大或多发性CA,安全可靠,疗效显著且复发率低,值得推广应用。     

尖锐湿疣患者合并宫颈高危型HPV感染的光动力治疗

目的探讨5-氨基酮戊酸光动力(ALA-PDT)治疗女性外阴尖锐湿疣合并宫颈高危型人乳头瘤病毒(HR-HPV)感染的有效性和安全性。方法将入组的合并宫颈HR-HPV感染患者,随机分为ALA-PDT治疗组和无治疗的对照组(年龄和性别相匹配)。治疗组给予20%ALA凝胶外敷于宫颈3小时后进行635nm红光照射,每周治疗1次,共计2次,治疗结束后随访3个月。对照组无任何治疗,直接进入3个月随访期。两组患者均在初诊及第3个月时,应用宫颈脱落细胞杂交捕获二代法(HC-Ⅱ)检测HR-HPV,比较两组的检测结果和不良反应情况。采用SPSS 17.0软件对实验结果进行统计学分析。结果入组的合并宫颈HR-HPV感染患者77人,治疗组38人,对照组39人。治疗结束后,治疗组HC-Ⅱ检测发现25人(65.8%)HR-HPV转阴,对照组仅4人(10.3%)转阴,治疗组转阴率明显高于对照组(χ2=25.282,P0.001)。治疗组中的不良反应包括:轻度到中度的疼痛、水肿、糜烂,没有发生治疗部位的感染、溃疡、瘢痕和畸形。结论 ALA-PDT是一种相对安全、有效的治疗宫颈HRHPV感染的方法。     

JNK信号通路在δ氨基酮戊酸-光动力疗法诱导SW480细胞凋亡中的作用机制

目的:探讨JNK信号通路在δ氨基酮戊酸(ALA)-光动力疗法((PDT)诱导SW480细胞凋亡中的作用.方法:将SW480细胞分为空白对照组、激光照射组、ALA组及ALA-PDT组.Western blot 检测各组细胞c-Jun氨基末端激酶(JNK)的表达;用SP600125(JNK抑制剂)预孵育ALAPDT组细胞,Western blot检测各组细胞的多聚(ADP-核糖)聚合酶(PARP)的表达.结果:磷酸化JND在空白对照组、激光照射组及ALA组几乎无表达,ALA-PDT后30-90min细胞表达显著高于空白对照组、激光照射组及ALA组(F=12.314,P＜0.001),其中ALAPDT后60及90min的磷酸化JNK表达显著高于ALA-PDT后30min(F=9.782,P＜0.001),各组细胞总的JNK表达无显著差异.JNK的激活能抑制ALA-PDT诱导sw480细胞凋亡.结论:JNK信号通路的激活抑制ALA-PDT诱导SW480细凋亡;JNK通路可能成为增强ALA-PDT治疗结肠癌的新靶点.     

ALA-PDT联合口服茶多酚对尖锐湿疣患者血清IL-2 IL-10 IL-12水平的影响

目的观察5-氨基酮戊酸光动力疗法(ALA-PDT)联合茶多酚对尖锐湿疣的疗效,以及对尖锐湿疣患者血清白细胞介素(IL)-2、IL-12、IL-10水平的影响。方法将102名尖锐湿疣患者随机分为3组:A组(单纯激光治疗组)、B组(单纯ALA-PDT组)、C组(ALA-PDT联合茶多酚组),每组各34人;另选30名健康人作为健康对照组(D组)。于术前和术后3个月,采用双抗体夹心酶链免疫吸附试验(ELISA),分别检测各组血清IL-2、IL-12、IL-10水平,对比分析各组血清IL-2、IL-12、IL-10水平变化及意义。结果治疗前,A组、B组和C组血清IL-2、IL-12水平低于D组,IL-10水平高于D组,差异均有统计学意义(A组与D组比较,t值分别为6.67,9.36,6.80;B组与D组比较,t值分别为8.14,12.22,8.79;C组与D组比较,t值分别,7.76,8.87,9.57;均P0.05);A组、B组和C组之间血清IL-2、IL-12、IL-10水平比较,差异无统计学意义(A组与B组比较,t值分别为0.51,1.25,1.08;A组与C组比较,t值分别为0.13,0.76,1.49;B组与C组比较,t值分别为0.43,0.25,0.55;均P0.05)。治疗后3个月,B组和C组血清IL-2、IL-12水平高于治疗前,IL-10水平低于治疗前,差异均有统计学意义(B组t值分别为4.44,9.22,9.10;C组t值分别10.65,9.86,11.99;均P0.05);B组和C组血清IL-2、IL-12、IL-10水平与A组比较,差异均有统计学意义(B组与A组比较,t值分别为2.59,2.11,2.35;C组与A组比较,t值分别7.35,3.56,4.12;均P0.05);B组和C组血清IL-2、IL-12、IL-10水平比较,差异有统计学意义(t值分别6.64,4.44,2.67;均P0.05)。结论 ALA-PDT联合茶多酚能治愈尖锐湿疣并防止其复发,其机制可能与升高IL-2、IL-12水平,降低IL-10水平有关。     

Hypericin activated by an incoherent light source has photodynamic effects on esophageal cancer cells

BACKGROUND AND AIMS: Photodynamic therapy (PDT) is a new treatment modality for early esophageal neoplasia. With two absorption maxima in the visible light range (550 and 588 nm) hypericin is a very promising photosensitizer for PDT with incoherent light sources. We studied the effects of photosensitizing hypericin in both primary cell cultures and cell lines (squamous: Kyse-140 and adenocarcinoma: OE-33) of human esophageal cancer using an incoherent white light source. MATERIALS AND METHODS: Esophageal cancer cells were preincubated (4-24 h) with hypericin (10 nM-1 micro M) and then irradiated with a light energy dose of 30 J/cm(2). RESULTS: Hypericin showed strong phototoxic effects and induced apoptosis in a dose-dependent fashion. The IC(50) value of hypericin phototoxicity was approximately 30 nM in both squamous and adenocarcinoma cells. In the concentrations used nonphotoactivated hypericin showed no toxic or apoptotic potency. The phototoxicity of hypericin was compared to that of delta-aminolevulinic acid (5-ALA), which is already being used for photodynamic therapy of gastrointestinal cancer. 5-ALA produced similar phototoxic effects but at a much higher dose (IC(50) 182+/-8 micro M in Kyse-140 and 308+/-40 micro M in OE-33 cells). Moreover, 5-ALA did not induce apoptosis to a relevant extent. CONCLUSION: Hypericin is a very promising new photosensitizer for innovative photodynamic therapy of esophageal cancer. Both the well known clinical safety of hypericin and the lower costs of broad band light sources argue in favor of clinical trials.     

Role of photodynamic therapy in the treatment of esophageal cancer

Photodynamic therapy (PDT), a treatment of choice for cancer, induces a photochemical reaction, thereby eradicating tumor cells. This is achieved through the administration of a photosensitizer drug, which is activated with a laser after localization to the tumor mass, and is an approved curative endoscopic ablative treatment for superficial esophageal squamous cell carcinoma (ESCC) in Japan. PDT has been approved for dysplastic Barrett's esophagus and as a palliative treatment for patients with symptomatic obstructive esophageal cancer in US. However, its adverse events and complicated procedure and the development of alternative endoscopic procedures such as endoscopic submucosal dissection, radiofrequency ablation and cryotherapy, have largely limited the practice of PDT in esophageal cancer worldwide. Recently, owing to the invention of second‐generation PDT using talaporfin sodium and diode laser, PDT can be performed with less phototoxicity and therefore has regained popularity in the treatment of ESCC. As a salvage treatment for patients with local failure after chemoradiotherapy (CRT), PDT has shown promising complete response with less phototoxicity and shorter sun shade period. In addition, the efficacy and safety of PDT in patients with local failure of ESCC after CRT were shown in several clinical trials. The direction of the study interest of the next‐generation PDT is the safety and potential expansion of the indications for its application in the future. This review covers the PDT for the treatment of ESCC and dysplastic Barrett's esophagus, with special focus on the role of PDT in practice for esophageal cancer.     

光动力疗法与支架放置术治疗进展期食管癌比较

目的对比光动力疗法与内镜下支架放置术对进展期食管癌的疗效和安全性。方法18例行内镜下光动力治疗，22例行内镜下支架放置术，根据患者的耐受情况辅助化疗。两组患者的年龄、性别、肿瘤大小、分期、合并症等相比，无统计学差异。对比两种治疗方法对进展期食管癌的疗效和安全性，观察毒副作用，随访生存时间。结果光动力治疗组平均随访时间6．7（0．5～19）月；临床症状缓解率77．8％（14／18）；内镜下完全应答率16．7％（3／18），部分应答率为38．9％（7／18）；半年生存率55．6％（10／18），1年生存率22．2％（4／18）；中位生存期为7个月。1例术后1周出现大出血，并发症发生率为5．6％（1／18）；未见光过敏等不良反应发生。支架术组平均随访时间3．5（1～19）月；临床症状缓解率81．8％（18／22）；半年生存率22．7％（5／22），1年生存率9．1％（2／22）；中位生存期为3个月。两组相比，半年生存率和中位生存期之间差异有统计学意义（P〈0．05）。结论光动力疗法与支架放置术均可显著改善进展期食管癌患者的临床症状，但前者更明显延长患者的生存期，是治疗进展期食管癌又一有效手段。     

Changing pattern of esophageal cancer incidence in New Mexico

OBJECTIVE: Multiple reports indicate that esophageal adenocarcinoma incidence has increased during the past 20 yr, especially in non-Hispanic white men. We retrospectively reviewed adenocarcinoma and squamous cell carcinoma cases in our heterogeneous state population to determine the effect of ethnicity on histology. METHODS: We searched the New Mexico Tumor Registry for all cases of esophageal cancer from 1973 to 1997. Inclusion criteria included histological diagnosis of adenocarcinoma or squamous cell carcinoma, self-reported ethnicity, and gender. Age-adjusted incidence rates for both adenocarcinoma or squamous cell carcinoma were compared among ethnic groups in 5-yr intervals. RESULTS: Six hundred fifteen patients met inclusion criteria. Esophageal adenocarcinoma age-adjusted incidence rates/100,000 increased significantly during the 25-yr period: 1973-1977, 0.25 cases; 1978-1982, 0.33 cases; 1983-1987, 0.45 cases; 1988-1992, 0.85 cases; and 1993-1997, 1.19 cases; p < 0.001. In comparison, squamous cell carcinoma age-adjusted incidence rates did not increase significantly during the study period. In non-Hispanic whites, the histological age-adjusted incidence rate changed during the 1993-1997 period compared to other periods: 1993-1997, squamous cell carcinoma 1.01 and adenocarcinoma 1.42, p < 0.001. In Hispanics, the age-adjusted incidence rate of adenocarcinoma increased significantly in the fifth period compared to other periods, p < 0.001. In all minority groups, squamous cell carcinoma remained the predominant type. CONCLUSIONS: Esophageal adenocarcinoma age-adjusted incidence increased in New Mexico from 1973 to 1997. This increase was found in non-Hispanic whites and Hispanics and became predominant in non-Hispanic whites. Squamous cell carcinoma remains the primary type in minorities. This study suggests that ethnicity may influence esophageal cancer histology or ethnic background may place an individual at increased risk for certain types of esophageal cancer.     

脂质体槲皮素对食管癌细胞增殖及蛋白表达的影响及机制

目的比较不同脂质体槲皮素对人食管癌Eca109和Eca9706细胞增殖的作用,并初步探讨其作用机制。方法采用旋转蒸发法制备氯仿和甲醇溶解类脂物质的脂质体槲皮素LQ1和按同比例的氯仿和DMSO作为溶剂的脂质体槲皮素LQ2,用DMSO直接溶解槲皮素制备非脂质体槲皮素nLQ,分别作用于Eca109和Eca9706细胞（分别作为LQ1、LQ2及nLQ组）,同时设立对照组。MTT实验检测各组细胞抑制率,免疫组织化学染色和免疫印迹法检测磷酸酶基因（PTEN）和细胞周期素D1（Cychn D1）蛋白表达。结果各组细胞增殖的抑制效应、上调PTEN和下调Cyclin D1蛋白表达的效应呈现同一趋势,即LQ2组〉LQ1组〉nLQ组〉对照组,P〈0．05。结论脂质体槲皮素对食管癌细胞增殖有抑制作用,LQ2的抑制率高于LQ1;上调PTEN表达、下调Cyclin D1表达可能为其作用机制之一。     

槲皮素对食管癌Eca109细胞迁移侵袭及血管生成的影响

目的研究槲皮素(Que)对人食管癌Eca109细胞迁移侵袭及血管生成的影响。方法分别用5μg/mL、10μg/mL Que处理Eca109细胞,通过平板克隆形成实验、创伤愈合实验及Transwell实验观察其克隆形成能力以及迁移和侵袭能力的改变。制备Eca109肿瘤条件培养基,诱导人脐静脉内皮细胞CRL-1730迁移及成管,观察Que对其的影响。采用蛋白质免疫印迹法(Western blot)测定Que对Eca109细胞的血管内皮生长因子-A(VEGF-A)、基质金属蛋白酶2(MMP2)、MMP9蛋白表达的影响。结果 10μg/mL Que可显著抑制Eca109细胞的单细胞克隆形成能力(P0.05),而5μg/mL Que则不影响Eca109细胞的单细胞克隆形成能力(P0.05)。10μg/mL Que可抑制Eca109细胞的迁移和侵袭(P0.05),5μg/mL Que仅抑制Eca109细胞的侵袭(P0.05),但并不明显影响其迁移(P0.05)。5μg/mL、10μg/mL Que均可抑制Eca109肿瘤条件培养基诱导的CRL-1730细胞迁移和管腔形成(P均0.05),且10μg/mL Que的效果更明显。10μg/mL Que可明显降低VEGF-A、MMP2和MMP9的表达(P均0.05),5μg/mL Que仅降低MMP2的表达(P0.05)。结论 Que可以抑制Eca109细胞的迁移、侵袭及血管新生,并呈剂量依赖性。     

Repeated talaporfin sodium photodynamic therapy for esophageal cancer: safety and efficacy

Esophagus - Talaporfin sodium photodynamic therapy (tPDT) is an effective salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Repeated tPDT could also be indicated...