二甲基苯并蒽诱导金黄地鼠颊囊癌的模型建立及组织学研究

用５ｇ／Ｌ二甲基苯并蒽（ＤＭＢＡ）丙酮溶液涂布地鼠颊囊粘膜每周３次，共６～１２周，观察癌变全过程。结果用药６周后有３７．５％地鼠颊囊粘膜表现为单纯性上皮增生，６２．５％为非典型性上皮增生；９周后有２５％为非典型性上皮增生；而７５％为原位癌；１２周后有１２．５％为原位癌，８７．５％为早期鳞状细胞癌；用药至第１２周而观察到１８周时，所有动物均为高分化鳞状细胞癌。丙酮无致癌作用。ＤＭＢＡ所诱导的地鼠颊囊癌类似于人类口腔颊部鳞状细胞癌，方法简便，诱癌时间较稳定，病理过程与人类相似，是一个实用性较强，又比较理想的口腔癌动物模型。     

分化诱导剂HMBA与丝裂霉素或顺铂联合应用对耐药MEC—1细胞的作用

研究发现分化诱导剂ＨＭＢＡ与抗癌药丝裂霉素（ＭＭＣ）或顺铂（ＣＤＤＰ）联合应用有可能提高耐药肿瘤细胞对抗癌药的敏感性。联合使用的效果与抗癌药的选择、给药方案及药物浓度有关。ＨＭＢＡ与ＭＭＣ合用可有效地增强ＭＭＣ对原来耐药的ＭＥＣ—１细胞抑制生长效果．ＨＭＢＡ与ＣＤＤＰ联合应用的效果则较差。若以很低浓度ＭＭＣ（０．０１μｇ／ｍｌ）先处理细胞５ｈ再加用Ｚｍｍｏｌ／ＬＨＭＢＡ，抑制细胞生长的效应为６６％，如将１ｍｍｏｌ／ＬＨＭＢＡ与１０μｇ／ｍｌＭＭＣ、或２ｍｍｏｌ／ＬＨＭＢＡ与１μｇ／ｍｌＭＭＣ同时应用，抑制细胞生长效应可达８０％。     

实验性口腔癌发生过程中增殖细胞核抗原表达的研究

目的：利用金黄地鼠颊癌模型，探讨口腔癌发生过程中增殖细胞核抗原（ＰＣＮＡ）表达变化及其规律。方法：０．５％二甲基苯并蒽（ＤＭＢＡ）丙酮液处理地鼠颊粘膜，每周３次，３、６、９和１２周分批处死动物；对照组不处理。利用抗ＰＣＮＡ单克隆抗体，免疫组化方法（ＬＳＡＢ）检测ＰＣＮＡ的表达情况。结果：正常地鼠颊粘膜ＰＣＮＡ表达主要位于基底层和少数棘层细胞，３周单纯增生类似正常，６￣９周上皮呈不同程度异常增生，Ｐ     

二甲基苯并蒽诱导金黄地鼠颊囊癌的模型建立及组织…

用５ｇ／Ｌ二甲基苯并蒽丙酮溶液涂布地鼠颊囊粘膜每周３次共６－１２周，观察癌变全过程。结果用药６周药有３７．５％地鼠颊囊粘膜表现为单纯性上增生，６２．５％为非典型上性皮增生；９周后有２５％为非典型性上皮增生；而７５％为原位癌；１２周后有１２．５％为原位癌，８７．５％为早期鳞状细胞癌；用药至第１２周而观察到１８周时，所有动物均为高分化鳞状细胞癌，丙酮无致癌作用。ＤＭＢＡ所诱导的地鼠颊囊癌类似于人类口腔     

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     

DMBA诱发金黄地鼠颊囊癌变的动态研究——光镜部分

用光镜观察致癌剂二甲基本并蒽（ＤＭＢＡ）诱发８９只金黄地鼠颊囊在不同时期的癌变过程，其结果显示，在连续涂布０．５％ＤＭＢＡ３周后出现轻度上皮异常增生，连续涂布５周即出现中度异常增生，６周至９周均出现重度异常增生甚至原位癌，提示０．５％ＤＭＢＡ诱发金黄地鼠颊囊出现异常增生的最初时间为第３周，６周后即已发展至原位癌，也进一步提示１～３周是研究金黄地鼠颊囊出现上皮异常增生的最初阶段。     

DMBA致地鼠颊囊粘膜癌变发生过程病损组织中MC的变化

在以０．５％ＤＭＢＡ丙酮液涂抹金黄地鼠颊囊粘膜癌变发生过程中的不同时期取材活检，镜下观察其组织学改变及肥大细胞的变化。结果显示，实验组地鼠颊囊粘膜结缔组织的肥大细胞较对照组增多，有显著性差异，乳头状增生时，肥大细胞增加达到高峰且聚集成巢状。提示在０．５％ＤＭＢＡ丙铜液涂抹金黄地鼠颊囊粘膜癌变发生过程中肥大细胞起到一定的作用。     

实验性口腔癌发生过程中增殖细胞核抗原表达的研究

目的：利用金黄地鼠颊癌模型,探讨口腔癌发生过程中增殖细胞核抗原（ＰＣＮＡ）表达变化及其规律。方法：０．５％二甲基苯并蒽（ＤＭＢＡ）丙酮液处理地鼠颊粘膜,每周３次,３、６、９和１２周分批处死动物;对照组不处理。利用抗ＰＣＮＡ单克隆抗体,免疫组化方法（ＬＳＡＢ）检测ＰＣＮＡ的表达情况。结果：正常地鼠颊粘膜ＰＣＮＡ表达主要位于基底层和少数棘层细胞,３周单纯增生类似正常,６～９周上皮呈不同程度异常增生,ＰＣＮＡ表达扩展至棘层,甚至全层,与异常增生程度呈正相关;１２周鳞癌形成时,ＰＣＮＡ表达明显增加,且见明显异质性。结论：ＤＭＢＡ诱导地鼠颊癌发生过程中存在ＰＣＮＡ异常表达,且与癌变进展有关,提示ＰＣＮＡ表达可作为口腔癌变监测的生物学标志之一。     

DMBA诱导的金黄地鼠颊囊粘膜癌变中超氧化物歧化酶动态观察

用ＤＭＢＡ诱导的金黄地鼠颊囊粘膜癌为模型，进行诱癌粘膜的光镜、电镜观察，并在诱癌的不同时期检测诱癌组织的总ＳＯＤ活性的动态变化。结果表明，诱癌粘膜总ＳＯＤ活性随ＤＭＢＡ处理时间的增加呈动态下降，表现为明显负相关关系（ｒ＝－０．９９７，Ｐ＜０．００１）。提示ＳＯＤ可作为诱癌过程的一个判断指标，可用于肿瘤防治的干预试验。     

绞股蓝阻断金地鼠颊囊癌变的光镜观察

采用二甲基苯并恩（ＤＭＢＡ）诱导金地鼠颊囊癌前病变模型，结果发现不典型增生以及原位癌最早出现时间分别为涂ＤＭＢＡ３周和６周，远期致癌情况最早出现于涂ＤＭＢＡ４周者。比以往报道时相提前。以单方和复方绞肌蓝喂服，经光镜观察发现：服药组比模型组６周时癌变率低；涂ＤＭＢＡ３周后远期观察不典型增生有逆转现象，提示绞股蓝有一定的防癌作用，单方与复方疗效无显著差别。     

抗凝剂协同平阳霉素治疗肿瘤的实验研究

肿瘤的抗凝治疗是近十几年采新开展起来的一个研究领域。主要是用改善血液流变和微循环状态来协同增强化疗效果。本实验在地鼠颊囊癌模型建立后,在用平阳霉素化疗的同时加用抗凝剂华法令协同治疗,结果加用华法令组的地鼠平均生存时间比单用化疗组和空白组延长,三组地鼠平均存活天数分别是51.9,37.9和27.3天(P<0.01)。华法令加化疗组地鼠肿瘤的生长速度也明显比另两组慢(P<0.01)。华法令的抗肿瘤作用被认为是多途径的。但主要是以抗凝从而协同化疗为主。华法令阻止凝血因子发挥功能而降低血粘度,防止血液瘀滞,确保各器官血供和免疫功能的发挥。由于肿瘤区血流的增加而使大量免疫因子和抗癌药运到瘤体内发挥作用,使肿瘤细胞更易暴露在免疫因子而前而受攻击和消灭,还可以减少癌栓形成和防止瘤细胞着床。此外华法令可能还有一些其它方面的抗肿瘤作用,尚有待进一步研究。     

Spontaneous regression of induced parotid gland tumors in rats.

Pellets of powdered DMBA were implanted in the parotid glands of inbred male Fischer rats, and all experimental animals in which the carcinogen was implanted for 8, 10, 12, and 14 weeks developed well-differentiated squamous-cell carcinomas. When the carcinogen was implanted for longer periods of time, tumors developed in a smaller percentage of the experimental animals. Also, the weight of the parotid glands continued to increase with time following implantation of DMBA, reaching its highest level after 10 weeks, and then gradually decreasing with time. Different possible explanations for the regression of the induced parotid tumors are offered.     

Lack of tumour potentiating effect of cryosurgery in hamster cheek pouch after short term carcinogen exposure

Hamster cheek pouch was treated with the topical carcinogen DMBA for 2, 4 or 6 weeks. Cryosurgery to part of the treated area did not produce any alteration in subsequent tumour development. This contrasted with previous studies where cryosurgery following 8 weeks of DMBA application potentiated subsequent tumour development.     

Effects of hydrogen peroxide on oral carcinogenesis in hamsters

The effects of twice weekly topical applications of hydrogen peroxide on the buccal epithelium of Syrian hamsters were studied. Animals were treated either with hydrogen peroxide alone, with hydrogen peroxide and the carcinogen 9, 10-dimethyl-1,2-benzanthracene (DMBA), or with DMBA alone. In animals treated with 30% H2O2 alone, histopathologic examination after 22 weeks revealed hyperkeratosis and hyperplasia in all animals with hyperchromatic cells and mild dysplasia in four of nine: no tumors were seen. In animals treated with DMBA alone, three of seven (43%) developed epidermoid carcinoma, while six of 11 (55%) of animals treated with DMBA plus 3% hydrogen peroxide and five of five (100%) of animals treated with DMBA plus 30% hydrogen peroxide (P = 0.054) developed carcinoma. Thus, hydrogen peroxide can, by itself, induce pathologic changes frequently associated with preneoplastic lesions; it may also augment carcinogenesis associated with DMBA.     

Evaluation of the carcinogenic potential of toluidine blue O in the hamster cheek pouch.

Toluidine blue O has been shown to have clastogenic and mutagenic effects when tested in vitro, suggesting that it may be a carcinogen. Because this might compromise its use for cancer screening, the carcinogenic potential of this dye was investigated in the hamster cheek pouch, an established in vivo carcinogenesis model. Male hamsters were divided into seven groups at age 5 weeks. The right pouches of four groups were painted three times weekly with 2% toluidine blue or the vehicle for toluidine blue, in conjunction with submaximal applications of 9,10-dimethyl-1,2-benzanthracene (DMBA) (groups II and III, 0.5% twice weekly), and groups IV and V, 0.1% three times weekly). The right pouches of two groups received DMBA only (group I, 0.5% three times weekly, the standard maximal amount, and group VI, 0.1% three times weekly). Group VII received toluidine blue (right pouches) and toluidine blue vehicle (left pouches) three times weekly. The extent of carcinomas and other abnormalities (scored histologically) did not differ among groups receiving the same amount of DMBA with and without toluidine blue or vehicle, and no abnormalities were seen in the pouches from group VII. These results demonstrate no effect of toluidine blue as a carcinogen, cocarcinogen, or promoter.     

Effect of 2 episodes of cryosurgery on carcinogen-treated hamster cheek pouch

Hamster cheek pouches were treated with the topical carcinogen DMBA for 8 weeks. 2 episodes of cryosurgery, located within the area of previous carcinogen application enhanced the neoplastic process by comparison with matched controls. Comparison with previous studies suggests that the 2 episodes of cryosurgery may have a greater effect in provoking overt malignancy than a single episode of cryosurgery.     

Effect of excisional wounding on DMBA -induced hamster tongue carcinogenesis

The purpose of this study was to investigate histologically the effect of wounding on the hamster tongue after pretreatment with DMBA. The animals in which the tips of the tongues were pretreated with DMBA for 8 weeks, subsequently excised, and had no treatment or received applications of acetone, showed epithelial dysplasias. The animals which had the same pretreatment, excision, and received additional post-excision applications of DMBA for 9–13 days, developed squamous cell carcinomas. However, the animals which were pretreated with DMBA for 8 weeks but had no excision, did not show any pathologic changes, even though they received additional applications of DMBA for 9–13 days. The animals which received no pretreatment with DMBA for 8 weeks hut had an excision, showed normal wound healing, even though they had a post-treatment with DMBA for 9-13 days. The results of the present study indicated that excisional wounding acted as a promotional stimulus in inducing the appearance of epithelial dysplasias or carcinomas of tongues initiated with the carcinogen DMBA.     

Effect of excisional wounding on DMBA-induced hamster tongue carcinogenesis

The purpose of this study was to investigate histologically the effect of wounding on the hamster tongue after pretreatment with DMBA. The animals in which the tips of the tongues were pretreated with DMBA for 8 weeks, subsequently excised, and had no treatment or received applications of acetone, showed epithelial dysplasias. The animals which had the same pretreatment, excision, and received additional post-excision applications of DMBA for 9-13 days, developed squamous cell carcinomas. However, the animals which were pretreated with DMBA for 8 weeks but had no excision, did not show any pathologic changes, even though they received additional applications of DMBA for 9-13 days. The animals which received no pretreatment with DMBA for 8 weeks but had an excision, showed normal wound healing, even though they had a post-treatment with DMBA for 9-13 days. The results of the present study indicated that excisional wounding acted as a promotional stimulus in inducing the appearance of epithelial dysplasias or carcinomas of tongues initiated with the carcinogen DMBA.     

ＵＢＩＯ联合中药治疗口腔糜烂型扁平苔藓的疗效研究

目的　探讨紫外线照射充氧自血回输 (UBIO)加中药对口腔糜烂型扁平苔藓的疗效作用。方法　把口腔扁平苔藓病人随机分为两组 ,分别在治疗前后测定血液流变学、红细胞免疫、甲皱微循环等指标。结果　U BIO组治疗后与治疗前相比管袢长度、流速变慢的异常率、低切全血粘度、高切全血粘度、血浆粘度、血沉、C3b R花环率、C3b 1C花环率均有显著差异 (P <0 .0 1) ,袢顶管径的异常率与治疗前相比也有明显变化 (P <0 .0 5 ) ;中药组治疗后与治疗前相比血浆粘度、血沉明显降低 (P <0 .0 1) ,而且管袢长度、流速变慢的异常率低于治疗前 (P <0 .0 5 )。结论　UBIO加中药对口腔扁平苔藓有显著疗效 ,明显优于纯中药治疗。