小鼠足容积的活体和离体测量

本实验建立小鼠足容积测量方法学并提供小鼠足容积的生理数值，为进一步研究实验性皮肤癌发生的免疫机制打下基础．根据毛细管放大原理，使用自制的小鼠足容积测量仪测量３５１只昆明种小鼠左右足容积，发现左右足容积几乎相等．另对１５０只小鼠左右足进行３６９次重复测量，发现合格测量超过９７％．不同体重小鼠足生长曲线研究表明，随着体重的增加，小鼠足容积渐趋于一定值，表明生长停止．并且体重２５ｇ以上小鼠活体离体足容积差接近一定值，这提示大龄小鼠足血管张力和容积基本恒定．     

Double nondisjunction during karyotypic progression of chemically induced Syrian hamster cell lines

The karyotypic evolution of three chemically induced cell lines of Syrian hamster embryo in culture are described. The only karyotypic alteration of one clone was a trisomy of chromosome #11, which presumably arose by nondisjunction after carcinogen treatment. A pure population of cells with the trisomy was observed repeatedly upon karyotyping of cells at the first three passages after cloning. However, at a late passage, apparently normal diploid cells appeared in the culture, which we propose resulted from a second nondisjunction of one chromosome #11, reverting the cells from trisomy 11 to disomy 11. The karyotypic evolution of two other cell lines also involved double nondisjunction, which resulted in duplication of a translocated chromosome and concurrent loss of the normal nonrearranged chromosome. Taken together with the reported findings of others, the results indicate that double nondisjunction is a mechanism in karyotypic progression during neoplastic development.     

The relationship between epithelial Ia expression and the inflammatory cell infiltrate during experimental oral carcinogenesis

Summary The development of oral epithelial expression of Ia antigens and its relationship to the presence of IL-2r⁺ (CD25⁺) cells was investigated in rats treated with the water soluble carcinogen 4-nitroquinoline-N-oxide (4NQO). Acetone fixed frozen sections of the palate and tongue were stained using an indirect immunoperoxidase technique and monoclonal antibodies to rat Ia (I-A & I-E) and IL-2 receptor. After 4 weeks 4NQO treatment all rats expressed oral epithelial Ia but thereafter (2–9 months) expression was present in only 20–40% of animals. Epithelial expression of Ia by histologically normal, dysplastic and neoplastic epithelium was always associated with the presence of an underlying inflammatory cell infiltrate containing CD25⁺ cells. Overall there were significantly more CD25⁺ cells in tissue specimens containing Ia⁺ epithelium compared with Ia^– epithelium. Furthermore, during the first 4 weeks of carcinogen treatment, a significant positive correlation was found between the CD25⁺ cell density and occurrence of focal epithelial Ia expression. These results, together with analysis of the T cell, NK cell, macrophage and B cell content of the infiltrates induced by 4NQO, suggest that the CD25⁺ cells represent activated T cells. Thus, our results in this experimental model are consistent with the idea that epithelial expression of Ia is the result of production of IFN- by locally activated T cells.     

UVA-induced tumours in pigmented hairless mice and the carcinogenic risks of tanning with UVA

Summary An animal experiment is presented in which two groups of pigmented hairless mice were exposed daily to suberythemal doses of UVA to study tumourigenesis. The aim of the study was to estimate the carcinogenic risks of tanning by UVA. The pigmented hairless mice, Skh-hr2, were separated by selective breeding into two groups, the browns and the blacks. Both groups were exposed daily to UVA from fluorescent UVA lamps (Philips TL40W/09) purified by rigorously filtering out the shorter wavelengths. No acute actinic damage was observed after any exposure. However, in most UVA exposed animals, especially in the blacks, a marked scratching preceded the development of tumours. Hyperkeratosis was also observed. All animals developed tumours. Histopathologically at least 60% of the tumours were squamous cell carcinomas. Depositions of melanophages were observed, but no melanomas. It is beyond any doubt that UVA is carcinogenic in laboratory animals. The present state of knowledge justifies no preference for tanning with UVA over tanning with UVB.     

Lanzoprazole promotes gastric carcinogenesis in rats with duodenogastric reflux

Background Duodenogastric reflux is known to cause an increased frequency of cancer in the glandular portion of the stomach in rats. Furthermore, it is debated whether inhibition of gastric acid secretion may promote gastric carcinogenesis. In the present study we examined the combined effect of gastroduodenal reflux and acid inhibition with respect to the development of gastric carcinoma in the rat.Methods Following the construction of a gastrojejunostomy in male Wistar rats, half of them were given the proton pump inhibitor lanzoprazole for 1 year. The rats were then killed and the pH in the stomach and gastrin in blood were measured. The stomach was examined macroscopically as well as histologically.Results Gastrin levels at autopsy were significantly increased in treated rats compared to the control group, confirming an effect of lanzoprazole on gastric acid secretion. Body weight was significantly reduced in the treated rats. Thirty of 79 rats developed gastric cancer, and they were all adenocarcinomas of the Lauren intestinal type. Gastric cancers occurred significantly more often in lanzoprazole-treated rats (50%) compared with controls (27%).Conclusion Lanzoprazole given orally enhances the carcinogenic effect of duodenogastric reflux in rats.     

核受体PXR在宫颈鳞癌组织及SiHa细胞中的表达及临床意义

目的:探讨核受体孕烷X受体(PXR)在宫颈鳞癌组织的表达及与宫颈鳞癌发生的关系。方法:采用免疫组织化学及细胞免疫化学检测核受体PXR在41例宫颈癌组织及宫颈鳞癌细胞株SiHa中的表达。结果:PXR在宫颈鳞癌细胞株SiHa中有表达;正常宫颈组织有PXR表达,41例宫颈鳞癌组织中PXR的阳性率为59.5%,且宫颈癌组织中明显低表达。结论:PXR的表达水平与宫颈癌的发生有一定的相关性,可能成为今后判断宫颈癌预后有价值的标志物。     

Ras、MAPK、CyclinD1与皮肤病理性瘢痕癌变相关性研究

目的探讨Ras/Raf/MAPK信号通路及其通路下游靶基因CyclinD1与病理性瘢痕癌变的相关性。方法 (1)激光扫描共聚焦显微技术,对病理性瘢痕和瘢痕癌组织进行K-ras、H-ras、N-ras免疫荧光双标记。(2)免疫组织化学SP法分别检测正常皮肤、病理性瘢痕和瘢痕癌三组组织中MAPK、Cy-clinD1蛋白的表达。(3)原位杂交技术检测三组组织中MAPK mRNA、CyclinD1 mRNA的表达。(4)用基因测序技术,检测病理性瘢痕上皮中K-ras、H-ras、N-ras第12、13位密码子突变。结果 (1)免疫荧光双标记:K-ras、H-ras、N-ras在病理性瘢痕上皮中呈现较弱荧光,为弱阳性表达;在瘢痕癌组织中呈现较强荧光,为强阳性表达。(2)MAPK及其mRNA和CyclinD1及其mRNA在正常皮肤表皮均呈阴性或弱阳性表达,在皮肤病理性瘢痕上皮中呈弱阳性表达,在瘢痕癌组织中呈强阳性表达。瘢痕癌组表达水平(阳性面积)、表达强度(平均吸光度)与正常皮肤、病理性瘢痕组比较,差异均有统计学意义(P<0.01);但正常皮肤组与病理性瘢痕组比较,差异无统计学意义(P>0.05)。(3)在病理性瘢痕中未发现K-ras、H-ras、N-ras第12、13位密码子突变。结论 (1)Ras、MAPK、CyclinD1蛋白及其MAPK mR-NA、CyclinD1 mRNA不是瘢痕上皮癌变的早期信号。(2)K-ras、H-ras、N-ras第12、13位密码子突变与病理性瘢痕上皮癌变无关。     

大鼠肺鳞癌发生发展过程中肿瘤血管生成及血液供应研究

目的　探讨肺癌发生发展过程中肿瘤血管生成和血液供应 ,以及血管内皮细胞生长因子(VEGF)及其受体Flk 1与肿瘤血管生成的关系。方法　 10 0只Wistar大鼠左肺下叶支气管灌注致癌质碘油 ,分批处死获取肺鳞癌癌变及进展期病变标本 ,使用油画颜料染成黄、绿两种颜色的液态硅橡胶分别灌注支气管动脉与肺动脉 ,免疫组化检测病变组织中VEGF、Flk 1的表达及vWF染色切片上的微血管密度 (MVD)。结果　经支气管动脉灌注黄色液态硅橡胶显示 ,肿瘤病灶呈黄色的新生血管团与曲张的支气管动脉相连通 ,镜下见癌巢间质肿瘤微血管腔充盈硅橡胶颗粒 ;经肺动脉灌注绿色液态硅橡胶 ,肿瘤区绿色的血管呈不连续的枯树枝、断枝、残枝状 ,与肿瘤血管不连续 ,镜下肿瘤微血管腔无硅橡胶颗粒。原位癌的MVD计数 ( 3 9.5 0± 12 .60 )与不典型增生 ( 8.92± 3 .80 )及侵袭癌 ( 61.0 5± 19.92 )比较 ,差异均有显著性 (P <0 .0 1)。从支气管粘膜上皮增生→鳞状化生→不典型增生→原位癌→侵袭癌 ,VEGF和Flk 1阳性系数逐渐升高。MVD与VEGF和Flk 1表达均呈正相关 (r分别为 0 .9798和 0 .90 78,P <0 .0 0 5 )。结论　肺癌新生血管形成是大鼠肺鳞癌发生发展的重要现象 ,新生的肿瘤血管与支气管动脉相连通 ,与肺动脉不相连通 ,证明肺鳞癌发生     

1578例大肠息肉的病理类型与癌变因素探讨

目的:探讨大肠息肉的各种病理类型与癌变相关因素.方法:选择2002年1月至2011年12月在本院肠镜检查检出大肠息肉患者1578例,回顾性研究大肠息肉的发病年龄、部位、大小、形态、病理类型与癌变因素.结果:大肠息肉检出率为22.72%,癌变率5.64%;不同年龄检出率有统计学差异(X2=8.250,P=0.016),中年患者检出率高;大肠息肉在直肠(32.00%)乙状结肠检出(35.80%)最常见,息肉直径≤1cm较常见(78.90%),在直径1cm-2cm的息肉中腺瘤性息肉占比最高(70.12%),形态研究发现无分叶状息肉较常见(80.04%);癌变因素研究发现老年患者(X2=10.070 P=0.002)、发生部位在直肠及乙状结肠(X2=0.843 P=0.016)、息肉直径>2cm(X2=114.173 P<0.001),分叶状息肉(X2=16.66 P<0.001)、三种腺瘤性息肉(X2=71.14 P<0.001)较其它因素癌变率显著增加.结论:大肠息肉的发病与年龄性别密切相关;不同病理类型的大肠息肉临床特点明显不同;直肠和乙状结肠、分叶、腺瘤性、直径>2.0cm的息肉是发生癌变的高危因素;对大肠息肉须及时治疗,定期随访,减少大肠癌的发生.     

桥本氏甲状腺炎并发甲状腺癌的临床病理学研究

目的 探讨桥本氏甲状腺炎并发甲状腺癌的临床病理学特征和癌发生的病理学基础。方法 采用HE染色和免疫组化法观察16例桥本氏甲状腺合并甲状腺癌和12例单纯甲状腺癌的病理学形态和基因蛋白的表达。结果 桥本氏甲状腺合并甲状腺主要为乳头状癌。镜下可见淋巴组织增生病变区甲状腺滤泡上皮细胞不典型增生,中度表达p53、Ki67、bcl-2和c-erbB-2,与癌组织的表达无显著差异（P＞0．05）,而极显著高于非甲状腺炎的癌旁组织（P＜0．01）。结论 桥本氏甲状腺炎合并甲状腺可能是在多基因协同作用下,残存的滤泡上皮细胞发生不典型增生而癌变。