大豆异黄酮防治白斑癌变的动物实验

目的探讨大豆异黄酮对口腔白斑癌变的防治作用。方法将60只雄性金黄地鼠随机分为4组,前6周(每周3次)在A、B组动物颊囊涂DMBA溶液,C组涂丙酮,D组正常饲养。接下来12周,每天给B组动物灌喂大豆异黄酮溶液,A、C组灌生理盐水。实验结束时处死动物,收集标本。结果与A组相比,B组肿瘤出现的平均时间稍晚,分别是(12·50±2·22)周和(13·30±1·49)周,其差异无统计学意义(P=0·30)。A组和B组相比,肿瘤的潜伏期和发生率差异均无统计学意义。结论在金黄地鼠颊囊黏膜癌模型中未发现大豆异黄酮对白斑癌变具有防治作用。     

螺旋藻对DMBA-TPA诱发地鼠口腔癌血管生成的研究

目的:通过研究螺旋藻对金黄地鼠口腔癌血管生成的影响,探讨螺旋藻对口腔癌的阻断作用机理,为临床应用提供理论依据.方法:91只金黄地鼠随机分为5组,阳性对照组及螺旋藻3个不同剂量的用药组,于地鼠左侧颊囊涂二甲基苯并蒽和12-O-四葵酰基-佛波-13-乙酸酯溶液,螺旋藻用药组在涂12-O-四葵酰基-佛波-13-乙酸酯的同时给予不同剂量(200mg/kg;400 mg/kg;800 mg/kg)的螺旋藻混悬液灌胃治疗,同时设阴性对照组.实验结束处死动物进行肿瘤血管生成相关指标的检测.结果:螺旋藻可显著降低地鼠口腔癌的血管密度,表明螺旋藻对血管生成有一定的抑制作用;但是对血管内皮生长因子没有影响.结论:通过抑制新生血管生成,螺旋藻可以阻断口腔癌前病变的进一步发展,但其抑制新生血管的机制需进一步探讨.     

金黄地鼠颊囊黏膜癌变过程中iNOS的表达与Bcl-2的关系

目的：观察金黄地鼠颊囊黏膜癌变过程中诱导性一氧化氮（inducible nitric oxide synthase，iNOS）的表达与凋亡相关蛋白Bcl-2的关系。方法：6—8周龄金黄地鼠72只，随机分为实验组（60只）和空白对照组（12只），空白对照组地鼠不做任何处理．实验组地鼠用0．5％的二甲基苯丙蒽（dimethyl-benzanthrance，DMBA）丙酮溶液诱导生成颊囊黏膜癌．并在黏膜癌变的不同阶段检测组织中iNOS和Bcl-2的表达。结果：正常地鼠颊囊黏膜组织中未见iNOS阳性表达．组织中iNOS、Bcl-2的表达强度在颊囊黏膜癌变过程中均呈上升趋势。鳞癌组织中iNOS的表达较单纯增生组织显著增强（P〈0．011；鳞癌组织中Bcl-2的表达强度明显高于轻度上皮异常增生组（P〈0．05），但与重度和中度上皮异常增生组之间无显著性差异（P〉0．05）；Bcl-2的表达强度随iNOS表达强度的增强呈现先升后降的复杂变化。结论：一氧化氮参与了颊囊黏膜鳞癌的发生、发展，并可能通过Bcl-2途径调节肿瘤细胞的凋亡。     

Regional lymph node metastasis created by partial excision of carcinomas induced in hamster cheek pouch with 9,10-dimethyl-1,2-benzanthracene

The feasibility of using the hamster cheek pouch/dimethyl-benzanthracene (DMBA) system as an experimental model of lymphatic metastasis was investigated. Forty male Syrian golden hamsters treated with DMBA were divided into two equal groups--one with surgical excision of their tumors and a control group without tumor excision. In the excision group, the animals received three applications/week to the left cheek pouch of 0.3% DMBA in acetone for 14 weeks. Following a three-week observation period, the tumors in the pouch were excised at their base, and the animals were killed after four weeks of further observation. In the control group, the animals were treated for 14 weeks in a manner similar to that used for the excision group, left for seven weeks without treatment, and then killed. Cheek pouches with tumors and cervical lymph nodes were processed for histological examination. All of the animals, both with and without metastasis, had borne squamous cell carcinomas (SCC) in their treated cheek pouches. Histologically, seven out of 16 animals in the excision group showed metastatic deposits of SCC confined to the left cervical lymph nodes, while in the control group, metastasis was not found in any of the 19 animals with SCC in their cheek pouches. The results demonstrate that surgical excision of the hamster cheek pouch carcinoma is efficient in producing unequivocal lymph node metastasis.     

螺旋藻对实验性口腔癌预防作用的研究

目的 研究螺旋藻对二甲基苯并蒽(DMBA)诱发的金黄地鼠口腔癌的预防作用。方法选用DMBA诱发金黄色地鼠口腔癌模型,同时用1.0g/kg、0.3g/kg螺旋藻进行预防,进行口腔肿瘤发生率、癌变率、微核细胞率、细胞增殖核抗原(PCNA)和上皮生长因子受体(EGFR)检测。结果螺旋藻高、低剂量组平均瘤负荷抑制率分别为74.2％和59.8%;癌变率、微核细胞率和PCNA标记指数与阳性对照组相比均明显降低,但对EGFR表达没有影响。结论螺旋藻对DMBA诱发的动物口腔癌有预防作用。     

过氧化苯甲酰在诱发金黄地鼠舌癌中的作用

目的：证实在癌变过程中,促癌剂和诱癌剂同样有着重要作用。方法：本实验通过二甲基苯并蒽（ＤＭＢＡ）涂抹金黄地鼠舌粘膜,并用２０％过氧化苯甲酰局部涂抹同一部位,每周２次,共２０周。同样方法分别涂布ＤＭＢＡ（对照组）和２０％过氧化苯甲酰（阴性对照组）。结果：对照组成瘤率９０％（２７／３０）,而实验组为１００％（３０／３０）,２组动物均经历了上皮异常增生、原位癌、浸润及转移癌几个阶段,但实验组在每一阶段较     

实验性口腔白斑癌变过程中端粒酶活性变化的研究

目的：研究金地鼠颊囊白斑癌变过程中端粒酶活性的动态变化规律,为探讨药物干预口腔白斑癌变可能作用机制提供基线资料。方法：以Salley法建立金地鼠颊囊癌变模型,55只金地鼠分两组：对照组（A组）5只;模型组（B组）50只。双盲法判别病理分级;TRAP—ELISA法检测标本端粒酶活性。结果：两组的端粒酶阳性率分别为：A组0％、B组52．27％,B组端粒酶阳性率随涂布DMBA周数（病理分级）具有显著性差异（p〈0．01或p〈0．05）。实验性口腔白斑癌变过程中,端粒酶活性逐渐上升。结论：端粒酶可以作为口腔白斑癌变化学预防的替代性终点标记物监测口腔白斑癌变。     

云芝糖肽对金地鼠颊囊白斑癌变过程中端粒酶活性化学预防作用研究

目的：探讨中药云芝糖肽（Yun Zhi Polysaccharopeptide，PSP）对实验性口腔白斑癌变过程的干预作用及其对端粒酶活性影响，探索PSP作为癌化学预防药物的可能药理机制。方法：以Salley法建立金地鼠颊囊癌变模型，PSP进行体内干预，110只金地鼠分4组：空白对照组（A组）；模型对照组（B组）：先、后服用PSP组（C组、D组）。双盲判别病理分级；TRAP-EUSA法检测标本端粒酶活性。结果：各组的端粒酶阳性率分别为：A组0％、B组52．27％，C组8．7％，D组26．92％。C组、D组与B组相同时段病理分级、端粒酶阳性率差异显著（p〈0．01或P〈0．05）；各处理组之间端粒酶活性在中度异常增生阶段差异明显。结论：PSP有确切的抑制实验性口腔白斑癌变的功效。端粒酶可能是PSP发挥癌化学预防作用的众多靶点之一，PSP抑制端粒酶活性的最佳时相是在中度异常增生阶段。     

Cancer-promoting effect of Taiwan betel quid in hamster buccal pouch carcinogenesis

OBJECTIVE: To investigate the cancer-promoting effect of Taiwan betel quid in hamster buccal pouch carcinogenesis.
MATERIALS AND METHODS: Two hundred and fifty-two non-inbred mate adult Syrian golden hamsters were randomly divided into six groups, each containing forty-two animalS. A treatment regimen over a 14-week experimental period was employed with six animals per group being killed at seven different periods (every 2 weeks). The right buccal pouch of each animal was painted three times a week with various combinations of 7, 12-dimethylbenz[a]anthracene (DMBA), Taiwan betel quid extract, dimethyl sulfoxide (DMSO) and mineral oil.
RESULT: Both the number and size of tumors in animals concurrently treated with DMBA and betel quid were significantly higher than those in animals treated with DMBA alone in each killing period of 8, 10, 12 and 14 weekS. No visible tumors but hyperkeratosis and acanthosis were observed in pouches treated with betel quid alone for all killing periods.
CONCLUSION: Our results indicate Taiwan betel quid may be a co-carcinogen in human oral carcinogenesis, if extrapolation can be made from the current animal study.     

Diurnal variation of γ-glutamyl transpeptidase activity during DMBA-induced hamster buccal pouch carcinogenesis

OBJECTIVE: The aim of the present study is to assess the diurnal variation of γ-glutamyl transpeptidase (GGT) during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis.
MATERIALS AND METHODS: The right buccal pouches of 108 Syrian golden hamsters, divided into three experimental groups, were treated three times weekly with 0.5% DMBA in mineral oil over an 11-week treatment regimen. The left buccal pouches were untreated and served as the controlS. Within each group, six animals were killed at 4-h intervals (04.00, 08.00, 12.00, 16.00, 20.00 and 24.00) for 24 h. GGT histochemical stain, according to the method of Ruthenberg and coworkers, was applied. The number of GGT-positive foci in the pouch mucosa was recorded at 3, 7 and 11 experimental weeks.
RESULT: Diurnal variation of GGT histochemical activity during DMBA-induced hamster buccal pouch carcinogenesis was substantiated in the present study.
CONCLUSION: This investigation highlights the importance of the diurnal variation in experimental oral carcinogenesis.     

Zyflamend对口腔黏膜癌变过程中前列腺素E2和白三烯B4水平影响的动物实验

目的 通过测定抗炎天然植物混合剂Zyflamend对地鼠口腔黏膜癌变过程中花生四烯酸代谢产物前列腺素( prostaglandin,PG) E2和白三烯B4水平的影响,探讨其可能的作用机制.方法 将27只金黄地鼠分为5组,阴性对照组3只,不涂药;其余24只用0.5％的二甲基苯并蒽( dimethylbenzanthracene,DMBA)涂于左侧颊囊3次/周,3周后将其按随机数字表随机分为4组(每组6只),阳性对照组不涂药,其余3组金黄地鼠分别于左侧颊囊分别涂低、中、高浓度Zyflamend(稀释比例分别为1∶3、1∶1和原液).每周涂药3次,第4周末处死动物取左侧颊囊速冻于液氮中行液相色谱-串联质谱法(liquid chromatographic tandem mass spectrometry,LC-MS/MS)分析.结果 阳性对照组PGE2为(0.377±0.290) μg/g,低、中、高浓度Zyflamend组的PGE2水平分别为(0.523±0.286)、(0.488±0.147)和(0.774±0.314) μg/g,低、中浓度组与阳性对照组相比差异无统计学意义(P＞0.05),高浓度组与阳性对照组相比差异有统计学意义(P＜0.05).与阳性对照组(0.135±0.046) μg/g相比,低、中、高浓度组白三烯B4水平均显著降低(P＜0.05),分别为(0.094±0.066)、(0.096±0.077)和(0.067±0.012) μg/g.结论 癌前病变的早期炎症阶段,Zyflamend能够抑制5-脂氧合酶途径中代谢产物白三烯B4的水平.     

一氧化氮在金黄地鼠颊囊粘膜癌变中的动态观察

目的:探讨金黄地鼠颊囊粘膜癌变过程中血清及组织中一氧化氮的作用,为口腔癌的预防及早期诊断寻找 一个新的检测指标。方法:用二甲基苯并萘(DMBA)诱导金黄地鼠颊囊癌变,并在诱导癌变的不同阶段检测血清 中一氧化氮的浓度及组织中iNOS的表达。结果:地鼠颊囊粘膜在由正常向鳞癌发展的过程中,血清NO浓度及组 织中iNOS的表达强度均呈上升趋势,鳞癌组血清NO浓度与正常粘膜组、单纯增生组、异常增生组相比均有显著性 差异(P<0.05);免疫组化显示,正常颊囊粘膜组织中未见iNOS阳性表达,鳞癌中iNOS的表达较单纯增生时显著 增强(P<0.01)。血清NO浓度与组织中iNOS的表达强度之间存在正相关关系(rB=0.590,P<0.01)。结论:一 氧化氮在口腔粘膜鳞癌的发生、发展中起着促进作用,可作为诱癌过程中的一个判断指标。     

增生平对实验性口腔癌预防作用的研究

目的：研究增生平对二甲基苯并蒽（ＤＭＢＡ）诱发金黄地鼠口腔癌的预防作用。方法;选用ＤＭＢＡ诱发金黄地鼠口腔癌模型,同时灌喂增生平６ｋ／ｋｇ,进行口腔肿瘤发生率、癌变率、微核细胞率、银染核仁组织区（Ａｇ－ＮＯＲ）、细胞增殖抗原（ＰＣＮＡ）和上皮生长因子受体（ＥＧＦＲ）检测。结果：增生平组平均瘤数且抵制率为５２．５％,平均瘤负荷抑制率为７０．７％。同时口腔上皮生长因子细胞率、ＡｇＮＯＲ的ＰＣＮＡ标记指     

The effect of dinitrochlorobenzene (DNCB) on dimethylbenzathracene (DMBA) carcinogenesis on hamster buccal pouch.

DNCB is an antigen that stimulates the cell-mediated response in a sensitized host. The purpose of this study was to define the effect DNCB would have on a standard model system for oral carcinogenesis, theorizing that tumorgenesis would be delayed or inhibited. Fifty-six Syrian hamsters were divided into four groups. In group A (DNCB/DMBA), the right buccal pouch of twenty animals was treated with 2% DNCB in orabase, twice a week, and 0.5% DMBA, three times a week, for 10 weeks. In group B, twenty animals received DMBA only. In group C, six animals received DMBA in Orabase. In group D, ten animals received DNCB in Orabase only. The animals were killed at 6, 12, 16, and 20 weeks. The results indicate that there were no differences in the latent period or in the histologic characteristics of the epidermoid carcinomas that developed. However, there was sensitization of the buccal pouch in pouches painted with DNCB, in that gross and histologic evidence of a delayed sensitivity reaction was demonstrated.     

erbB expression changes in ethanol and 7, 12- dimethylbenz (a) anthracene-induced oral carcinogenesis

Objetive: The aim of this study was to determine erbB expression in normal mucosa, oral dysplasia, and invasive carcinomas developed in the hamster’s buccal pouch chemical carcinogenesis model. Study design: Fifty Syrian golden hamsters were equally divided in five groups (A-E); two controls and three experimental group exposed to alcohol, DMBA, or both for 14 weeks. Number of tumors per cheek, volume, histological condition, erbB expression were determined and results were analyzed by the Mann–Whitney U and Dunn’s test. Results: Control groups and those exposed to alcohol (A, B and C respectively) only presented clinical and histological normal mucosa; while those exposed to DMBA or DMBA plus alcohol (D and E groups) developed dysplasia and invasive carcinomas. erbB2, erbB3, and erbB4 increased their expression in alcohol-exposed mucosa, dysplasia, and invasive carcinomas. We observed a similar expression level for erbB2 in dysplasia and carcinomas; while, erbB3 and erbB4 were similar only in carcinomas. Conclusion: The DMBA and alcohol can be considered as carcinogen and promoter for oral carcinogenesis. The erbB expression is different according to their histological condition, suggesting differential participation of the erbB family in oral carcinogenesis induced by alcohol and DMBA. Key words:erbB, 7,12- dimethylbenz(a)anthracene, oral squamous cell carcinoma.     

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目的 探讨夏枯草对二甲基苯并蒽（DMBA）诱发的金黄地鼠口腔癌的化学预防作用。方法 2006年3月在首都医科大学口腔医学院研究所将30只金黄地鼠分3组：阴性对照组（6只）不涂药;阳性对照组（12只）涂0.5%DMBA于左侧颊囊,每周3次,共涂3周;夏枯草组（12只）前3周处理同阳性对照组,3周后换涂1%夏枯草,每周3次,涂1周。第4周末实验结束处死所有地鼠,处死前2 h腹腔注射50 mg／kg的5-溴脱氧尿嘧啶（5-bromo-2’-deoxyuridine,BrdU）。取左侧颊囊行组织病理学观察和BrdU免疫组化染色。结果 与阳性对照组相比,夏枯草组颊囊单纯增生和异常增生的病灶数目均有所降低,其单纯增生病灶数目与阳性对照组比较差异有统计学意义（P < 0.05）。夏枯草组炎症细胞数（52.25 ± 18.53）个／mm2与阳性对照组（158.65 ± 26. 51）个／mm2相比,差异有统计学意义（P < 0.01）。夏枯草组 BrdU阳性率与阳性对照组相比有所降低,但二者差异无统计学意义。结论 夏枯草对DMBA诱发的金黄地鼠的炎症和口腔癌前病变的单纯增生有一定的抑制作用,但对于异常增生和细胞增殖抑制作用不明显。     

Apigenin prevents deregulation in the expression pattern of cell-proliferative,apoptotic, inflammatory and angiogenic markers during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

ObjectiveMalignant tumour arises due to abnormal cell proliferation, chronic inflammation, defect in apoptotic pathway and unwanted angiogenesis. The present study has investigated the modulating effect of apigenin on expression pattern of apoptotic (p53, Bcl-2, Bax, Caspase-3 and 9) cell proliferative (PCNA, Cyclin D1, c-fos), angiogenic (VEGF) and inflammatory (NFκB, COX-2) markers during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis.Materials and methodsOral squamous cell carcinoma was developed in the buccal pouches of golden Syrian hamsters by painting with 0.5% DMBA three times a week for 14 weeks. Deregulation in the expression of the cell proliferation, apoptosis, inflammation and angiogenesis markers was noticed in hamsters treated with DMBA alone.ResultsOral administration of apigenin at a dose of 2.5 mg/kg bw prevented the deregulation of the above mentioned molecular markers in hamsters treated with DMBA.ConclusionOur results thus suggest that apigenin exhibited anti-cell proliferative, anti-inflammatory, anti-angiogenic and apoptotic potential during DMBA-induced hamster buccal pouch carcinogenesis.     

Alpha tocopherol alters the distribution of Langerhans cells in DMBA-treated hamster cheek pouch epithelium

Thirty-seven adult male and female golden hamsters (Mesocricetus auratus) were divided into four experimental groups. In Group A, the animals served as untreated controls, having the left buccal pouches painted with mineral oil. In Group B, the animals received 10 mg vitamin E (alpha tocopherol) in peanut oil by the oral route, with a fine pipette, twice weekly. In Group C animals, the left buccal pouch was painted three times weekly with DMBA (0.5% solution of 7,12 dimethylbenz(a)anthracene in heavy mineral oil). Group D animals received both vitamin E and DMBA in the amounts indicated for Groups B and C, with the vitamin E being administered on days alternate to the DMBA painting, also in the manner described for the above groups. All animals were killed after eight weeks of treatment. Epithelial whole mounts were prepared from the left buccal pouches. These specimens were then stained for ATPase to demonstrate the presence of Langerhans cells (LCs). A notably decreased density of LCs was observed after treatment with DMBA. Vitamin E administration in addition to DMBA treatment resulted in a less dramatic decrease in LC density. Since vitamin E has been shown to retard experimental oral carcinogenesis, vitamin E may retard carcinogenesis by maintaining the number of Langerhans cells.     

齐留通和塞来昔布对实验性口腔癌抑制作用的研究

目的通过局部应用5-Lox抑制剂齐留通和Cox-2抑制剂塞来昔布,研究它们对DMBA诱发的金黄地鼠口腔癌的抑制作用.方法用0.5%的DMBA石蜡油涂于地鼠左侧颊囊,每周3次,共涂6周.从第7周开始分别给地鼠左侧颊囊局部涂抹3%和6%的齐留通、3%和6%的塞来昔布及3%齐留通与3%塞来昔布的混合物,每周3次,连续18周.结果通过局部应用3%和6%的齐留通,鳞状细胞癌的发病率从76.9%分别下降到45.8%(11/24,P＜0.05)和32.1%(9/28,P＜0.01);应用3%和6%的塞来昔布分别下降到57.6%(15/26,P＞0.05)和50.0%(12/24,P＜0.05);用3%齐留通与3%塞来昔布的混合物组,鳞状细胞癌的发病率降至36%(9/25,P＜0.01).用药后齐留通组的白三烯B4水平降低;塞来昔布组的前列腺素E2水平降低;联合用药组前列腺素E2和白三烯B4同时降低.结论齐留通和塞来昔布能够抑制DMBA诱发的金黄地鼠口腔癌的发生.齐留通和塞来昔布预防肿瘤的机制可能与其抑制异常花生四稀酸代谢酯氧化酶和环氧合酶途径有关.     

乳香酸与姜黄素对二甲基苯并蒽诱导地鼠口腔癌的化学预防作用

目的 观察乳香酸和姜黄素对二甲基苯并蒽(7,12-dimethyl benzanthracene,DMBA)诱导的叙利亚金黄地鼠口腔癌的化学预防作用、两者单独和联合应用是否可以抑制口腔癌的发生及发展,并对其抗肿瘤机制进行初步探讨.方法 实验对象为160只6～8周龄、体质量80～130 g的雄性叙利亚金黄地鼠,取10只为阴性对照组,不作任何处理;其余150只金黄地鼠用0.5％ DMBA涂抹左侧颊囊6周,第7周时采用随机数字表法将地鼠分为5个用药组和1个阳性对照组(每组25只),低浓度乳香酸组、高浓度乳香酸组、低浓度姜黄素组、高浓度姜黄素组及联合用药组分别给予5、10 mg/L乳香酸溶液,5、10 μmol/L姜黄素溶液及5 mg/L乳香酸+5μmol/L姜黄素溶液涂抹地鼠左侧颊囊18周,阳性对照组不做任何处理.第25周处死全部动物,记录肉眼肿瘤发生率、肿瘤数目及体积,行HE、5-溴脱氧尿苷(5-bromodeoxyuridine,BrdU)、免疫组化染色及花生四烯酸代谢物检测.结果 肉眼可见肿瘤发生率阳性对照组为93.8％,低浓度乳香酸组80.0％,高浓度乳香酸组81.3％,低浓度姜黄素组78.3％,高浓度姜黄素组75.0％,联合用药组73.9％;各用药组平均肿瘤数目均较阳性对照组[(2.19±0.98)个]有所降低,其中高浓度姜黄素组[(1.45±0.92)个]和联合用药组[(1.13±0.81)个]显著下降(P＜0.05,P＜0.01);各用药组组织病理学观察鳞状细胞癌病变数目均较阳性对照显著降低(P＜0.05).各用药组与阳性对照组相比均能降低BrdU增殖指数,尤以低、高浓度姜黄素组和联合用药组效果更佳(P＜0.05);高、低浓度乳香酸组、高浓度姜黄素组及联合用药组白三烯B4含量与阳性对照组相比均显著下降(P＜0.05).结论 各用药组均可明显抑制DMBA诱导的金黄地鼠口腔癌,其中联合用药组抑癌作用效果最好,乳香酸和姜黄素可以通过降低细胞增殖活性抑制DMBA诱导的金黄地鼠口腔癌的发生、发展.