两种建立金黄地鼠颊囊癌模型方法的对照研究

目的二甲基苯并蒽丙酮注射法建立金黄地鼠颊囊癌动物模型,并与传统涂抹法相比较,为颊囊癌研究提供理想的动物模型。方法随机将81只金黄地鼠分为注射组、涂抹组和空白对照组。DMBA丙酮注射组60只地鼠,将注射浓度预设为0.5%、0.4%、0.3%、0.2%、0.1% 5个组,每组12只地鼠,每周两次,于注射后每周进行大体观察、监测体重并计算肿瘤生长率,至3、6、9、12周麻醉后各处死3只,进行组织学观察;涂抹组15只地鼠,以0.5% DMBA丙酮涂抹,每周三次,至6、9、12、15、18周后麻醉处死3只;空白对照组不做任何处理,于12周全部处死行组织学观察。结果注射浓度组04%、03%、0.2%、0.1% 分别在13,9,12,16周时出现约为0.8 cm×0.6 cm×0.5 cm大小的肿瘤;12周时成瘤率分别为25%、87%、42%、58%;死亡率分别为48%、11%、13%、10%;相比0.5% DMBA丙酮涂抹组,12周时成瘤率为48%,死亡率为37%,至18周时才出现颊黏膜高分化鳞癌。结论经筛选采用03% DMBA丙酮液注射法可诱发形成口腔鳞癌动物模型,缩短建模周期,降低建模成本,能为科学研究提供较为理想的动物模型。     

绿茶儿茶素对于DMBA诱发大鼠乳腺癌前增生的抑制作用

目的:探讨GTC(Greenteacatechins,绿茶儿茶素)对于DMBA(9,10-Dimethylbenz-1,2-anthrancene,二甲基苯蒽)诱发的大鼠乳腺癌前增生的抑制作用。方法:42只7周龄雌性SD大鼠,随机分为A(空白对照)、B(DMBA灌胃)、C(GTC灌胃)、D(DMBA/GTC灌胃)4组。于实验开始日,B组和D组的大鼠一次性DMBA油溶液灌胃(7mg/100g体重);自实验开始日起,C组和D组的大鼠每日GTC水溶液灌胃1次(80mg/次)。4组大鼠均自由摄食基础饲料和饮用自来水,至实验结束。光镜下(100倍)计量各组大鼠乳腺导管的芽体、实团、乳头状增生和核分裂象等4项增生指标,并计算其平均值(x±s)。结果:1)B组的芽体、实团、芽体+实团、乳头状增生和核分裂象均显著地高于与其对照的A组;2)D组的实团、芽体+实团显著高于与其对照的C组,实团、乳头状增生较C组趋低;3)D组的芽体、实团、芽体+实团和乳头状增生显著低于B组,核分裂象在两组之间没有显著性差异;4)C组的各项增生指标均低于A组,但无显著性差异。结论:持续GTC水溶液灌胃可明显抑制DMBA诱导的大鼠乳腺的癌前增生。     

头颈部癌放疗后诱发第二癌

随着放射治疗治愈率的提高,晚期并发症也随之增多,放射诱发癌就是其中之一,作者在短期内遇到4例,报道如下:例1 杜××,男60岁,17年前(1970年2月)因鼻咽未分化癌放射治疗,~(60)Co照射肿瘤量7,035cGy/38次/55天,结束时鼻咽及颈部皆阴性。约10年后右耳经常流水,8月前右耳听力下降,右耳区阵发性病,进行性加重。1987年1月检查见右耳道内充满粉红色新生物,易出血。鼻咽及颈部无肿块。右耳新生物活检为分化性鳞癌;X片双侧硬化性乳突炎。行中耳照射4,000cGy,肿瘤未缩小而改行手术治疗。例2 章××,男50岁,10年前舌根右侧鳞癌Ⅱ-Ⅲ级,于1976年12月在本院~(60)钴放疗。舌根部     

血管生成与DMBA诱发的大鼠乳腺癌转移的关系

目的：探讨肿瘤血管生成与乳腺癌转移的关系。方法：采用二甲基苯蒽（ＤＭＢＡ）诱发的大鼠乳腺癌模型,以免疫组织化学染色方法检测肿瘤组织微血管密度（ＭＶＤ）及血管内皮生长因子（ＶＥＧＦ）表达。结果：转移组原发瘤灶ＭＶＤ及瘤细胞ＶＥＧＦ表达显著的高于非转移组（分别Ｐ〈０．００１和Ｐ,０．０２）及良性肿瘤组（两者均Ｐ〈０．００１）。结论：ＶＥＧＦ介导的血管生民在促进乳腺癌转移的过程中可能起重要作用。     

鼻咽癌放射后诱发癌9例报告

 本文报告我院1975～1988年收治鼻咽癌放疗后诱发癌9例,占0.27%(9/3368)。对放疗诱发癌可采用手术、放射、化疗或综合治疗。     

DMBA诱导大鼠乳腺癌模型及乳腺癌化学预防实验研究进展

本文介绍DMBA诱导大鼠乳腺癌模型介绍、COX-2抑制剂及植物提取物的实验研究,讨论以DMBA诱导大鼠乳腺癌模型为基础的乳腺癌化学预防实验研究进展.     

鼻咽癌放射后诱发癌9例报告

本文报告我院1975～1988年收治鼻咽癌放疗后诱发癌9例,占0.27％(9/3368)。对放疗诱发癌可采用手术、放射、化疗或综合治疗。     

沥青烟气诱发小鼠皮肤肿瘤的实验研究

焦油沥青有强烈的致皮肤癌作用已为人们所熟知,但以往实验采用的都是皮肤涂沫的方法,而许多职业工人经常接触的是沥青烟气,为此,我们模拟工人工作现场的实际情况,用加热产生的沥青烟气熏染小鼠,观察皮肤肿瘤发生情况,将100只昆明种小鼠随机分为2组(A,B组),A组小鼠每天在一密闭染毒柜中薰染煤焦沥青烟气3h,     

中国地鼠口腔颊囊黏膜癌模型的建立及癌变的动态观察

目的: 利用二甲基苯并蒽(DMBA)涂抹法建立中国地鼠颊囊黏膜癌的实验动物模型,观察癌变不同时期的组织学动态变化过程。方法: 将60只雄性中国地鼠随机分为3组,分别为模型组(24只)、溶剂对照组(12只)、空白对照组(24只)。溶剂对照组仅涂丙酮液,空白对照组不作任何处理,模型组以0.5% DMBA涂抹中国地鼠两侧颊囊,每周3次,共15周。分别于第6、9、12、15周将模型组和空白对照组随机处死6只,溶剂对照组处死3只,在肉眼及光镜下动态观察颊囊黏膜癌变全过程的形态学和显微组织学改变。结果: 与对照组比较,DMBA长时间处理后模型组地鼠相继出现口腔内黏膜充血、增厚、溃烂化脓、白斑及菜花状赘生物等变化,经历了单纯上皮增生(6~9周)、不同程度上皮异常增生(9~12周)、原位癌及鳞状细胞癌(12~15周)等阶段。结论: DMBA涂抹法可成功建立中国地鼠颊囊黏膜癌前病变、鳞状细胞癌模型,发病过程与人类口腔鳞状细胞癌相似,为口腔鳞癌的多阶段、多步骤研究提供了一个较为理想的动物模型。     

Isolation and characterization of normal hamster buccal pouch stem/stromal cells – A potential oral cancer stem/stem-like cell model

The hamster buccal pouch (HBP) is an appropriate experimental model for buccal squamous cell carcinoma (SCC). Our objective was to isolate and characterize the stem/stromal cells from normal HBP. HBP stem/stromal cells were successfully derived from three of five normal pouch tissues, which differentiated into adipogenic, chondrogenic, and osteogenic lineages, and also expressed stem cell and differentiation markers, indicating their stem cell origin and differentiation capability. These cells showed high expression of CD29, CD90, and CD105, markers specific for bone marrow stem cells, and exhibited very low expression of CD14, CD34, and CD45, markers specific for hematopoietic cells. Of the HBP stem/stromal cells isolated, 90% stained positively for cytoplasmic keratin, whereas 10% stained positively for vimentin. In conclusion, normal HBP stem/stromal cells provide a potential avenue for future experimental trials of cancer stem/stem-like cells for treatment of buccal SCC. In vitro, we may detect the sequential changes of normal HBP stem/stromal cells during multistep oral carcinogenesis or the alternations of these cells upon irradiation treatment and/or chemotherapy.     

Combination chemoprevention of hamster buccal pouch carcinogenesis by bovine milk lactoferrin and black tea polyphenols

Combination chemoprevention is a promising approach for oral cancer prevention. The authors evaluated the combined chemopreventive effects of bovine milk lactoferrin (bLF) and black tea polyphenols (Polyphenon-B) in a clinically relevant in vivo model of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Although dietary administration of bLF and Polyphenon-B alone significantly reduced the tumor incidence, combined administration of bLF and polyphenon-B was more effective in inhibiting DMBA-induced genotoxicity and development of HBP carcinomas by modulation of carcinogen-metabolizing enzymes and cellular redox status. These results suggest that a “designer item” approach will be useful for human oral cancer prevention strategies.     

DMBA-induced hamster buccal pouch carcinoma and VX2-induced rabbit cancer as a model for human oral carcinogenesis

In this article, we have described and compared the advantages and disadvantages of two potential animal cancer models (the hamster buccal pouch cancer model and the VX2-induced rabbit cancer model) for human squamous cell carcinomas of the oral mucosa. Currently, no animal cancer model is perfectly applicable to human oral squamous cell carcinomas. This is because the hamster buccal pouch cancer model has a different etiology and genetic constitution compared with human oral carcinomas. In addition, the VX2-induced rabbit cancer model is not produced in situ and, consequently, its natural behavior is totally reliant on the location of transplantation. Nonetheless, with the use of these two animal cancer models together, researchers could evaluate different aspects of the cellular and molecular biological characteristics or assess potential novel treatment regimens for squamous cell carcinomas of the human oral mucosa.     

DNA hypomethylation of proliferating cell nuclear antigen gene in human hepatocellular carcinoma is not due to cell proliferation

Proliferating cell nuclear antigen (PCNA) gene expresses preferentially in proliferative cells or tissues. The levels of PCNA mRNA are very low in livers of adult mammals. Expression of PCNA gene in hepatocellular carcinoma tissues was, however, elevated; and 5′-CCGG-3′ sequences of the gene in neoplastic tissue were less methylated. Such DNA hypomethylation was concluded, on the basis of two observations, not to be due to the cell proliferation in hepatoma tissues. First, while the expression of PCNA was increased during serum-stimulation of quiescent Hep G2 cells, the DNA methylation pattern of PCNA gene remained unchanged. Second, in rat liver regeneration, the PCNA mRNA level rose and declined, but the DNA methylation status of PCNA gene was unaltered. Therefore, the DNA hypomethylation of the PCNA gene found in hepatocellular carcinoma was not due to cell proliferation, but a possible consequence of cell transformation.     

人颊癌细胞信号转导抑制因子1沉默对细胞增殖及化疗药物敏感性的影响

目的:探讨人颊癌细胞中细胞因子信号转导抑制因子1（SOCS1）沉默与细胞增殖及化疗药物敏感性影响的关系。方法:Western blot、PCR及定量PCR验证SOCS1干扰序列沉默人颊癌细胞系BcaCD885中SOCS1的表达。MTT法检测颊癌细胞对化疗药物敏感性的变化。细胞计数法观察细胞的增殖速度。流式细胞术检测细胞周期的变化。结果:将SOCS1干扰序列转染BcaCD885细胞后,SOCS1 mRNA及蛋白表达水平均明显下降。SOCS1表达抑制后,转染72h后,BcaCD885细胞数量较对照组显著减少（P＜0.05）。化疗药物卡铂和紫杉醇对BcaCD885细胞的半数抑制浓度（IC50）均显著降低（P＜0.01）。SOCS1表达抑制后BcaCD885细胞G0/G1期细胞比例明显升高,而S期和G2/M期细胞比例明显降低,与对照组比较,差异均具有统计学意义（P＜0.05）。结论:SOCS1基因沉默后,人颊癌细胞株BcaCD885的增殖能力下降,并增强对化疗药物的敏感性。     

两种食管鳞癌细胞系增殖和侵袭能力的比较研究

目的：研究两种来源不同的食管鳞癌细胞系EC109和KYSE510分裂增殖能力和侵袭能力的差异。方法：利用MTT实验和侵袭实验,在体外分别检测EC109和KYSE510细胞的分裂增殖能力和侵袭能力;采用裸鼠皮下接种实验和爪垫皮下接种淋巴结转移模型,比较两种细胞在体内的成瘤能力、局部侵袭能力和区域淋巴结转移能力的差异;免疫印迹检测上皮-间充质细胞转换标志蛋白E-cadherin、γ-cadherin和Vimentin在两种细胞中的表达水平。结果：体外实验表明,EC109细胞的分裂增殖和侵袭能力均明显较KYSE510细胞的强（P〈0.05）;皮下接种和爪垫皮下接种淋巴结转移实验显示EC109细胞的成瘤能力、局部侵袭能力和淋巴结转移能力均较KYSE510细胞的高;免疫印迹检测发现,E-cadherin和γ-cadherin在EC109细胞中的表达水平较KYSE510细胞中的表达低,而Vimentin在EC109细胞中的表达则较KYSE510细胞中的表达高,提示EC109细胞发生上皮-间充质细胞转换的程度较KYSE510的高。结论：EC109细胞的增殖和侵袭能力均较KYSE510细胞的强,上皮-间充质细胞转换可能是导致这种差异的原因之一。     

Survivin 在喉癌中的表达及与细胞增殖的相关性研究

目的：探讨凋亡抑制蛋白Survivin在喉癌中的表达及其与细胞增殖的相关性。方法应用免疫组化（ SP）法和流式细胞术对63例喉鳞状细胞癌组织及15例正常喉组织进行Survivin蛋白检测和DNA含量分析。结果 Survivin在正常喉组织中不表达,在喉癌标本中阳性表达为45/63（71．4％）,其阳性表达与分化程度及有无淋巴结转移有关（P＜0．05）,而与患者年龄、性别、临床分期无关（P＞0．05）。喉癌的DNA指数（DI）和增殖指数（PI）均比喉正常组织高（P＜0．05）,且PI值与Survivin阳性表达呈正相关（P＜0．05）。结论在喉癌中Survivin均有表达,其可能导致喉癌细胞过度增殖,影响喉癌的发生和发展,可能成为今后喉癌诊断和治疗的新靶点。     

食管鳞状细胞癌DNA含量和倍体分析的临床意义

目的:研究食管鳞状细胞癌DNA含量的分布及倍体类型与其生物学行为的关系。方法:采用流式细胞技术对手术切除的106例食管鳞癌患者新鲜标本进行DNA分析,分析DNA含量、S期细胞分数、增殖指数及倍体类型与食管鳞癌浸润深度、淋巴结转移、病理分级及分期等生物学行为的关系。结果:食管鳞癌患者异倍体出现率为82.08%。DNA含量、S期细胞分数、增殖指数随TNM分期增加呈现逐渐增高的趋势,但与肿瘤浸润深度(T分期),病理分级不相关。有淋巴结转移组食管鳞癌S期细胞分数和增殖指数均高于无淋巴结转移组,DNA含量两组间差异并无统计学意义。异倍体食管鳞癌DNA含量、S期细胞分数、增殖指数及淋巴结转移均明显高于二倍体食管鳞癌。结论:食管鳞癌DNA含量的分布及倍体类型与其生物学行为相关,DNA分析是评估食管鳞癌预后、制定术后治疗方案的一个有价值的参数。     

Selectivity of the photosensitiser Tookad for photodynamic therapy evaluated in the Syrian golden hamster cheek pouch tumour model

The response to photodynamic therapy (PDT) with the photosensitiser (PS) Tookad was measured in the Syrian hamster cheek pouch model on normal mucosae and chemically induced squamous cell carcinoma. This PS is a palladium-bacteriopheophorbide presenting absorption peaks at 538 and 762 nm. The light dose, drug dose and drug injection-light irradiation times (DLI), ranging between 100 and 300 J cm(-2), 1-5 mg kg(-1) and 10-240 min respectively, were varied and the response to PDT was analysed by staging the macroscopic response and by the histological examination of the sections of the irradiated cheek pouch. A fast time decay of the tissular response with drug dose of 1-5 mg kg(-1) was observed for DLI ranging from 10 to 240 min and for light doses of 100-300 J cm(-2) delivered at a light dose rate of 150 mW cm(-2). A significantly higher level of tissular response was observed for squamous cell carcinoma compared to normal tissue. Nevertheless, the threshold level of the drug-light dose for a detectable response was not significantly different in the tumoral vs normal tissue. The highest response at the shortest DLIs and the absence of measurable response at DLI larger than 240 min at light dose of 300 J cm(-2) and drug dose of 5 mg kg(-1) reveals the predominantly vascular effect of Tookad. This observation suggests that Tookad could be effective in PDT of vascularised lesions.