p53蛋白表达与HPV16感染相关新疆维吾尔族妇女宫颈癌的关系

目的 探讨p53蛋白表达在HPV16型感染相关的新疆维吾尔族妇女宫颈癌发生发展中的作用。方法 采用半巢式PCR和免疫组化技术检测79例新疆维吾尔族妇女宫颈癌组织中HPV16 DNA和p53蛋白表达情况，探讨其与宫颈癌发生的相关性。结果 在宫颈癌组织中，HPV16检出率为81．0％（64／79），高于对照组7．5％（3／40），二者存在显著性差异（x^2=58．328，P=0．000）。宫颈癌组中p53蛋白阳性率为68.4％（54／79），明显高于正常宫颈组织12．5％（5／40），二者在统计学上有显著性差异（x^2=33．140，P=0．000）。结论 高危型HPV E6介导的p53蛋白降解失活是宫颈癌发生的重要机制之一，但在部分HPV感染的宫颈癌组织中p53蛋白表达蓄积的现象提示宫颈癌的发生还涉及到其它多基因和多步骤的致癌机制。     

HPV16感染p53及MDM2蛋白表达在宫颈癌中的意义

目的：检测新疆维吾尔族（维族）宫颈癌中HPV16感染、p53和MDM2蛋白表达情况，探讨三者在宫颈癌致癌机制中的相互作用及意义。方法：应用半巢式PCR及免疫组化方法检测79例宫颈鳞癌（实验组）、40例正常宫颈组织（对照组）中HPV16 DNA和1753、MDM2蛋白表达，结果：1）实验组中HPV16 DNA检出率为81．O％（64／79），高于对照组7．5％（3／40），两组比较有显著性差异（x^2=58．328，P=0．000）、2）实验组中p53蛋白表达率为68．4％（54／79），高于对照组12．5％（5／40），两组比较有显著性差异（x^2=33．140，P=0．000）.3）实验组中MDM2蛋白表达率为39．2％（31／79），高于对照组10．0％（4／40），差异有显著性（）（x^2=10．936，P=0．001）。结论：时HPV感染和p53、MDM2蛋白表达关系的分析显示，在大多教HPV阳性的宫颈癌中p53和MDM2蛋白表达一致，其相互作用在宫颈癌的发生、发展中具有重要意义；在HPV阴性的宫颈癌中，可能主要由MDM2基因通过p53依赖和p53非依赖两条途径发挥致癌作用另外．HPV、p53和MDM2也可能各自具有独立的致癌作用.     

不同宫颈病变p53突变与表达关系的研究

目的：探讨抑癌基因p53外显子7－8突变与表达在不同宫颈病变中的相互关系和意义。方法：免疫组化、PCR－SSCP分析。结果：p53外显子7－8突变与p53蛋白阳性在宫颈癌分别7／49例与24／49例,有显著差异（P＜0．01）;在宫颈不典型增生是8／51例与16／51例,无显著差异（P＞0．01）;在宫颈慢性炎症是0／57例与3／57例,未见突变。无论p53一子7－8突变还是p53蛋白阳性在宫颈癌与不典型增生之间均无显著差异（突变：P＞0．9;表达：P＞0．1）,在宫颈癌与宫颈慢性炎症之间均有显著差异（突变：P＜0．02;表达：P＜0．001）。同一标本p53外显子7－8突变不一定p53蛋白阳性。结论：p53外显子7－8突变和p53蛋白结构异常都是形成宫颈癌的重要且早期的因素,但在宫颈癌p53外显子7－8突变不是致p53蛋白结构异常而失活的主要因素。     

FHIT基因微卫星变异及人乳头瘤病毒感染与宫颈癌关系的研究

目的：探讨脆性组氨酸三联体（FHIT）基因微卫星变异及人乳头瘤病毒感染与宫颈癌的关系。方法：选取FHIT基因的两个微卫星多态标记，采用聚合酶链反应（PCR）法对50例宫颈癌及40例宫颈上皮内瘤样病变（CIN）组织进行杂合性丢失（LOH）、微卫星不稳定性（MI）及HPV16感染的检测。结果：在D3S1234位点上宫颈癌和C1N的LOH发生率分别为46％（23／50）和40％（16／40），差异无统计学意义，P=0．361；宫颈癌和CIN的MI发生率分别为18％（9／50）和12．5％（5／40），差异无统计学意义，P=0．339。在D3S4103位点上宫颈癌和CIN的LOH发生率分别为40％（20／50）和37．5％（15／40），差异无统计学意义，P=0．491；宫颈癌和CIN的MI发生率分别为14％（7／50）和7．5％（3／40），差异无统计学意义，P=0．265。但宫颈癌在两位点上LOH和MI发生频率均高于CIN且高级别CIN发生率高于低级别CIN。在50例宫颈癌组织中HPV16感染阳性组的LOH和MI发生率分别为79．5％（35／44）和31．8％（14／44），阴性组LOH发生2例，MI发生1例，两组间LOH的差异有统计学意义，P=0．003，MI的差异无统计学意义，P=0．645。在40例CIN中HPV16感染阳性组的I，0H和MI发生率分别为82．4％（14／17）和35．3％（6／17），在HPV16感染阴性组中I。0H和MI的发生率分别为52．2％（12／23）和17．4（4／23）；LOH的差异有统计学意义，P=0．048，MI的差异无统计学意义，P=0．274。结论：FHIT基因的变异可能发生在宫颈癌变的晚期。     

原发性非小细胞肺癌中K－ras基因突变的研究

目的探讨非小细胞肺癌（Non－smallcelllungcancer,NSCLC）组织中K－ras第12密码子点突变与NSCLC发生和发展的相关性。方法采用针对K－ras基因第12密码子特异点突变方式的引物进行PCR及银染法,分析175例新鲜NSCLC手术切除标本、43例癌旁组织及5例良性肺部疾患组织中K－ras基因第12密码子中CGT、GTT和GAT三种不同点突变方式。结果175例NSCLC组织中出现K－ras12密码子GGT→CGT突变率为34．86％（61／175）,GGT→GTT突变率40．57％（71／175）及GGT→GAT突变率37．71％（66／175）,总突变率为62．3％（109／175）。其中,同时出现CGT／GTT二个点突变为10．1％(11／109),CGT／GAT9．2％(10／109),GTT／GAT12．8％(14／109),而CGT／GTT／GAT均出现突变占23．9％(26／109)。其中Ⅰ期、Ⅱ期、Ⅲ期突变率分别为64．3％、56．8％及64．0％,另外腺癌突变率为63．8％、鳞癌为60．5％及腺鳞癌为64．5％,因此K－ras点突变与肺癌的分期及病理类型均无相关性（P＞0．05）。然而,37例腺癌突变组中出现GTT／GAT突变率为17．2％(10／58)明显高于鳞癌的3．5％(3／86),二者具有明显差异（P＜0．01）。43例癌旁组织与5例良性肺部疾患组织均未发现K－ras点突变。结论K－ras12密码子点突变及多点突变普遍存在于NSCLC中,其中肺腺癌出现GTT／GAT二个点突变明显高于鳞癌,结果提示K－ras基因点突变是肺癌发生和发展的一个重要因素。     

人类乳头瘤病毒及其亚型在新疆南部地区维族妇女宫颈癌组织中的分布

目的：研究我国宫颈癌高发区新疆维吾尔自治区维族妇女宫颈癌发病与人类乳头状瘤病毒（HPV）的关系。方法：采用聚合酶链反应（PCR）技术对南疆维族宫颈癌新鲜组织及正常宫颈组织（各40例）进行HPV－C、HPV16、HPV18及HPV6／11的检测。结果：HPV－C、HPV16、HPV18及HPV6／11在宫颈癌组织中的阳性率分别为87．5％、72．5％、10．0％及0％，在维族对照组中的阳性率分别为20．0％、5．0％、0及7．5％，在HPV－C阳性的宫颈癌中HPV16阳性占82．8％。宫颈癌组织中HPV－C及HPV16的阳性率明显高于正常对照组，差异有显著性（P＜0．001）。HPV16在宫颈鳞癌组织中的阳性率明显高于腺癌，而HPV18在宫颈腺癌中的阳性率明显高于鳞癌，HPV总感染率及HPV16阳性率在宫颈癌的各临床分期及病理组织分级之间无显著性的差异。结论：HPV感染与我国癌颈癌高发区新疆南部地区维族宫颈癌发病有密切相关，其中HPV16感染在南疆维族妇女宫颈癌发病中起主要的作用，HPV16主要与鳞癌有关，而HPV18与宫颈腺癌有关。HPV－C及HPV16感染与宫颈癌临床分期及病理分级无关。     

食管鳞癌中HPV—16／18感染与c—erbB—2、p53和Rb表达及其意义

目的：探讨食管鳞癌组织中人乳头瘤病毒HPV－16／18感染与c-erbB-2，p53和Rb表达及其意义。方法：采用聚合酶链反应（PCR）法检测90例活检存档的食管鳞癌蜡块中HPV－16／18的感染情况。从中随机选择20例，采用免疫组化法检测单独的HPV－16感染及c-erbB-2，p53和Rb表达。结果：PCR检测食管癌组织HPV－16／18的感染率为31．1％（28／90）；免疫组化法检测食管癌组织中单独的HPV－16的感染率为55％（11／20）。食管癌组织表达c-erbB-2，Rb和p53和Rb的阳性率分别为75％（15／20），65％（13／20）和80％（16／20）。HPV－16感染与c-erbB-2，Rb和p53表达之间未见相关性。HPV－16感染以及c-erbB-2，p53和Rb表达与淋巴结转移之间差异无显著性（P＞0．05）。p53表达与食管癌组织学分级之间差异有显著性（P＜0．05），而PV－16感染以及Rb和c-erbB-2表达与食管癌组织学分级之间差异无显著性（P＞0．05）。结论：食管癌组织中HPV－16／18感染与c-erbB-2，p53和Rb表达之间的关系是复杂的，尚有待于进一步研究。     

脆性组氨酸三联体基因在宫颈癌前病变和宫颈癌中的表达及其与p53和HPV16/18的关系

目的 探讨脆性组氨酸三联体（FHIT）基因缺失与p53的过度表达和人乳头状瘤病毒16和（或）18（HPV16／18）感染在宫颈癌前病变（CIN）和宫颈癌（CC）发生发展中的作用和意义。方法 采用免疫组化SP法检测52例CIN和69例CC中的FHIT基因和p53的表达,以原位杂交方法检测HPV16／18感染情况,并以18例正常宫颈组织作为对照。结果 FHIT在正常宫颈组织（正常组）中呈阳性表达;FHIT在宫颈CIN组中的阴性率为30．8％,在CINⅢ期的表达,明显高于正常组和CINⅠ、Ⅱ期（P〈0．01）;在CC组中阴性率为66．7％（46／69）,明显高于正常组和CIN组（P〈0．01）,且随细胞分化的降低,FHIT阴性率上升。p53和HPV16／18在CC组的阳性率分别达56．5％（39／69）和84．1％（58／69）,均高于CIN和正常组（P〈0．05）,且CC组的p53阳性率随细胞分化的降低而升高（P〈0．01）。CIN和CC组的FHIT阳性和阴性者,p53阳性率差异均无统计学意义（P〉0．05）,相关性分析也显示无相关关系;但两组FHIT阴性者的HPV16／18感染率明显高于FHIT正常表达者（P〈0．01）,FHIT与HPV呈负相关关系。结论 FHIT基因缺失与宫颈癌发生有关,它在CIN中的缺失可能可作为高危型CIN人群的筛选和宫颈癌早期诊断指标。CIN和CC中的FHIT缺失常与p53过度表达同时存在,但两者间无相关性。HPV16／18可能是引起FHIT和p53异常的共同原因。     

PCR-SSCP法检测宫颈癌P53基因突变

 目的：探讨抑癌基因P⁵³突变与宫颈癌发生发展之间的关系,并为该病的临床检测提供一种分子生物学方法。方法：应用多聚酶链反应－单链构象多态性（PCR SSCP）分析方法对宫颈癌及慢性宫颈炎组织中P⁵³基因5～6外显子的突变进行了检测。结果：35例宫颈癌组织中有2例出现突变,突变率为5.71%;而作为对照的慢性宫颈炎组织中无一例出现突变。结论：宫颈癌的发生与抑癌基因P⁵³5～6外显子的突变有关;此方法可有效地检测抑癌基因P⁵³的突变。     

原发性非小细胞肺癌中K-ras基因突变的研究

目的：探讨非小细胞肺癌（Non－small cell lung cancer NSCLC）组织中K－ras第12密码子点突变与NSCLC发生和发展的相关性。方法：采用针对K－ras基因第12密码子特异点突变方式的引物进行PCR及银染法,分析175例新鲜NSCLC手术切除标本、43例癌旁组织及5例良性肺部疾患组织中K－ras基因第12密码子中CGT、GTT和GAT三种不同点突变方式。结果：175例NSCLC组织中出现K－ras 12密码子GGT→CGT突变率为34．86％（61／175）,GGT→GTT突变率40．57％（71／175）及GGT→GAT突变率37．71％（66／175）,总突变率为62．3％（109／175）。其中,同时出现CGT／GTT二个点突变为10．1％ 11／109CGT／GAT 9．2％10／109 GTT／GAT 12．8％ 14／109,而 CGT／GTT／GAT均出现突变占23．9％26／109。其中Ⅰ期、 Ⅱ期、Ⅲ期突变率分别为64．3％、56．8％及64．0％,另外腺癌突变率为63．8％、鳞癌为60．5％及腺鳞癌为64．5％因此K－ras点突变与肺癌的分期及病理类型均无相关性（P＞0．05）。然而,37例腺癌突变组中出现GTT／GAT突变率为17．2％ 10／58明显高于鳞癌的3．5％3／86二者具有明显差异（P＜0．01）。43例癌旁组织与5例良性肺部疾患组织均未发现K－ras点突变。结论：K－ras12密码     

人乳头瘤病毒感染和p53基因突变与宫颈癌的关系

目的：探讨人乳头瘤病毒１６ 和１８ 型及抑癌基因ｐ５３ 突变对宫颈的致癌作用以及 Ｈ Ｐ Ｖ 感染与ｐ５３ 基因突变的相关性。方法：采用聚合酶链反应（ Ｐ Ｃ Ｒ） 技术和限制性酶切片段多态性分析（ Ｒ Ｆ Ｌ Ｐ） 技术对３４ 例原发性宫颈癌组织及３０ 例正常宫颈组织 Ｈ Ｐ Ｖ１６ ,１８ 型 Ｄ Ｎ Ａ 及抑癌基因ｐ５３ 的突变进行了检测。结果： Ｈ Ｐ Ｖ１６ ,１８ Ｄ Ｎ Ａ 在宫颈癌的总阳性率为６４７ ％ （２２／３４） ,正常宫颈组织只有６７ ％ 阳性,８例宫颈癌组织出现ｐ５３ 基因第６ 外显子突变,其中２ 例为 Ｈ Ｐ Ｖ１６ Ｄ Ｎ Ａ 阳性、１ 例 Ｈ Ｐ Ｖ１８ Ｄ Ｎ Ａ 阳性。结论：宫颈癌的发病与 Ｈ Ｐ Ｖ 感染及ｐ５３ 基因突变有关,宫颈癌组织中ｐ５３ 基因突变与 Ｈ Ｐ Ｖ 感染无关。     

Elderly Japanese women with cervical carcinoma show higher proportions of both intermediate-risk human papillomavirus types and p53 mutations

The p53 mutation has been found only in 0-6% of cervical carcinomas. In light of recent studies demonstrating that mutation of p53 gene was found in over 20% of the patients with vulvar carcinoma, a disease of elderly women and a known human papillomavirus (HPV)-related malignancy, we analysed mutation of the p53 gene in 46 women with cervical carcinomas at the age of 60 or more (mean; 71 years, range; 60-96 years). The presence of HPV and its type were analysed by polymerase chain reaction (PCR)-based assay using the consensus primers for L1 region. Mutation of the p53 gene was analysed by PCR-based single-strand conformation polymorphism and DNA sequencing technique. Point mutation of the p53 gene was detected in 5 out of 46 (11%) cervical carcinomas: 1 of 17 (6%) samples associated with high-risk HPVs (HPV 16 and HPV 18) and 4 of 27 samples (15%) with intermediate-risk HPVs (P= 0.36) whereas no mutation was found in 2 HPV negative cases. The mutated residues resided in the selective sequence known as a DNA-binding domain. The immunohistochemistry revealed the overexpression in cancer tissues positive for p53 mutation. All of the observed mutations of the p53 gene were transition type, suggesting that the mutation may be caused by endogenous mutagenesis. Although falling short of statistical significance reduces the strength of the conclusion, data presented here imply that p53 gene mutation, particularly along with intermediate-risk HPV types, may constitute one pathogenetic factor in cervical carcinoma affecting elderly women.     

p53 mutations in cervical carcinogenesis--low frequency and lack of correlation with human papillomavirus status.

p53 gene aberrations are common in human malignancies, and recent studies suggest that in cervical carcinoma p53 function is inactivated either by complex formation with human papillomavirus (HPV) E6 product or by gene mutation. Using polymerase chain reaction (PCR) followed by denaturing gradient gel electrophoresis (DGGE), we examined the mutational status of the four ''hotspot'' regions of the p53 gene in 47 primary cervical carcinomas. HPV status was determined, also by PCR. In 20 of these cases, we examined for loss of heterozygosity (LOH) on chromosome 17p13. In the 47 carcinomas, and in a further 68 biopsy specimens from normal, premalignant and malignant cervix, we investigated aberrant immunocytochemical expression of p53. Immunocytochemically, abnormal p53 expression was detected in 13 of 115 cases (8/57 carcinomas). Somatic mutation in p53 was detected in 1 of 47 cervical carcinomas; 36 were positive for HPV 16, 18 or 33. A low level of allele loss (3 out of 20 cases) was detected on chromosome 17p, occurring in both HPV-positive and HPV-negative cases, and in cases with and without p53 mutations. We conclude that somatic mutation in the hotspot regions of the p53 gene occurs infrequently in cervical carcinomas; that immunocytochemically detectable levels of p53 are also infrequent; and that there is no consistent correlation between p53 mutational status, LOH on chromosome 17p or HPV status in these cancers.     

The effects of p53 status and human papillomavirus infection on the clinical outcome of patients with stage IIIB cervical carcinoma treated with radiation therapy alone

BACKGROUND: It has been suggested that the p53 tumor suppressor gene regulates the radiosensitivity in human malignancies after irradiation; however, in cervical carcinoma, the role of the p53 gene is still unclear because of inactivation of functional p53 by infection with human papillomavirus (HPV). The objective of this study was to clarify the effects of p53 status and HPV infection on the clinical outcome of patients with cervical carcinoma after undergoing radiation therapy. METHODS: Fifty-two patients with International Federation of Gynecology and Obstetrics Stage IIIB squamous cell carcinoma of the cervix who received radiation therapy alone were reviewed. The combination of external beam irradiation therapy and three sessions of intracavity brachytherapy irradiation was performed for all patients. Genomic DNA extracted from paraffin embedded tissues was examined for HPV types 16, 18 and 33 by the polymerase chain reaction (PCR) method and for p53 status by PCR-single-strand conformation polymorphism (PCR-SSCP) technique. The effects of HPV infection, p53 status, and other parameters on clinical outcome were investigated by univariate analysis. RESULTS: HPV-DNA was detected in 40 patients (76.9%), and 14 patients (26.9%) had mutations of the p53 gene in the study. There was a significant correlation between the existence of HPV and p53 status (P < 0.001). Mutations of the p53 gene were detected in 6 of 12 patients (50%) who had local recurrent tumors, whereas p53 were wild type in 32 of 40 patients (80%) who achieved local control. The p53 mutation had a significant correlations with local tumor recurrence. Furthermore, p53 status caused statistical significant differences in the curves of the recurrence free survival rate and local control rate as determined by the log rank test (P = 0.02 and P = 0.03, respectively). Conversely, no obvious correlation with any clinical outcome for patients with cervical carcinoma was found concerning HPV infection. CONCLUSIONS: It is possible that the p53 gene may be used as a predictive factor in radiation therapy for patients with Stage IIIB squamous cell carcinoma of the cervix.     

Functional interaction of p53 with HPV18 E6, c-myc and H-ras in 3T3 cells.

Wild-type (wt) p53 has been suggested to be the product of a tumor-suppressor gene. Recently, it has been shown that the E6 oncoproteins of human papillomavirus (HPV) types 16 and 18, like the SV40 large T antigen, are physically associated with wt p53. We have investigated the functional interaction of wt p53 with the viral oncogene products of HPV16 and 18 and with cellular oncogenes by transfection of NIH3T3 cells with p53 wt alone or with several oncogene(s). We found that over-expression of HPV18 E6, c-myc or activated H-ras, like SV40 large T, can partially overcome the growth-inhibitory effect of wt p53 in NIH3T3 cells, while HPV16 E6 and E7, HPV18 E7, k-fgf, c-fos and mutant (mt) p53 do not. Further studies indicate that HPV18 E6 and c-myc can overcome the antiproliferative effect, but not the antitransforming effect, of wt p53, while activated H-ras can overcome both the antiproliferative and antitransforming effects of wt p53. These data show evidence of a functional interaction between HPV18 E6 and wt p53, and suggest that the cooperation of HPV E6 and cellular oncogenes c-myc and H-ras, which are activated in several cases of human cervical cancers, may be necessary to overcome completely the anti-oncogenic function of p53 in the development of these tumors.     

p53和HPV—16、18E6蛋白在宫颈癌的表达

目的探讨宫颈癌中抑癌基因p53蛋白与HPV-16、18癌基因E6蛋白的表达及其意义.方法采用SP免疫组织化学方法,检测68例宫颈癌和8例慢性宫颈炎上皮组织中p53和HPV-16、18E6蛋白的表达.结果68例宫颈癌中有17例p53蛋白和60例HPV-16、18E6蛋白呈阳性表达,阳性率分别为25.0%和88.2%.p53蛋白阳性表达与组织学类型有关,其阳性率在宫颈腺癌中为83.3%和宫颈鳞癌中为17.2%,有极显著性差异(P＜0.01);p53蛋白表达也与临床分期相关,该蛋白阳性表达率随着临床分期上升而增高.p53表达同肿瘤分化程度,淋巴结转移无关(P＞0.05).HPV-16、18E6蛋白在宫颈癌组织中的表达同肿瘤分化程度、淋巴结转移、组织学类型和临床分期无关(P＞0.05).在慢性宫颈炎上皮组织中均无p53和HPV-16、18E6蛋白表达.结论p53蛋白阴性和弱阳性表达以及HPV-16、18E6蛋白过度表达与宫颈癌发生有关,但在宫颈腺癌和临床分期升高的宫颈癌组织中,p53蛋白阳性表达的增强可能是p53基因突变的结果,或者与其他细胞蛋白结合,阻止了HPV-16、18E6蛋白对p53蛋白的降解作用,使p53蛋白稳定性增加和阳性表达水平提高.     

HPV16-E6/E7 Oncogene Mutation and p53 Expression among Indonesian Women with Cervical Cancer

Objective: To characterize HPV16 E6/E7 mutation and its association with p53 expression among Indonesian women with cervical cancer. Methods: This is a cross-sectional study involving 31 Indonesian women with pathologically proven cervical cancer and HPV16 infection. Data about the clinical characteristics of the study population were obtained from the medical records. Biopsy specimen of the cervical cancer mass from each study participant was obtained for DNA isolation. The ORFs of E6 and E7 genes were amplified using specific primer designed according to K02718/HPV16R gene sequence obtained from GenBank. Sequencing was performed using software program MEGA10. HPV16 E6 and E7 prototype sequences for nucleotide alignment (HPv16. P, GenBank Access code: NC_001526) was selected from European variant. The sequence of nucleotide and amino acid was aligned using software program BioEdit. p53 expression was evaluated through immunohistochemistry and quantified using immunoreactivity score (IRS). Results: Twelve subjects (38.7%) present with E6 and E7 mutation. Median age, parity, stage and histologic type of the tumour did not associate with E6/E7 mutation. E6 and E7 mutation rate was 25.8% (8/31) and 12.9% (4/31), respectively. Seven single nucleotide changes were identified within the E6 and E7 oncogenes, including four non-synonymous and three synonymous mutations. E6 T27C was the most prevalent mutation (16.1%). Nonsynonymous mutations were more prevalent within E7 gene (9.6%) (N29T, N29S, and R77C). Median IRS did not differ between HPV16-E6/E7 variants and wildtype (p value = 0.990). There was no association between E6/E7 mutations and p53 expression in Indonesian women with cervical cancer (PR 1.4, 95% CI: 0.29-6.77, p value = 0.704). Conclusions: HPV16 E6 mutation was more prevalent than E7 mutation among Indonesian women. There was no association between E6/E7 mutation and p53 expression level.     

Frequent occurrence of p53 gene mutations in uterine cancers at advanced clinical stage and with aggressive histological phenotypes.

The clinical and pathological significance of mutation of the p53 tumor-suppressor gene was examined in 108 cases of primary uterine cancers using single-strand conformation polymorphism and direct DNA sequencing analyses. Mutation of the p53 gene was detected in 19 (31%) of 62 cases of cancer of the uterine corpus and was more frequent in groups at an advanced clinical stage and/or with aggressive histology. Among four adenocarcinomas arising in the lowest portion of the uterine corpus, three showed integration of human papillomavirus (HPV) types 16 and/or 18 DNA, and two of them also showed p53 mutation. In cancer of the uterine cervix, p53 mutations were rare; 7% (3/46) in total, 3% (1/30) of cases with integration of HPV types 16 and/or 18 DNA and 13% (2/16) of cases without HPV DNA integration. Three mutations were detected among two cases at clinical stage IV and two cases of undifferentiated cervical carcinoma. Immunohistochemically, all five cases of uterine cancer which showed diffuse (> 50% of cancer cells) nuclear staining of p53 protein also carried the p53 mutation. Therefore, p53 alterations were suggested to be involved in the development of uterine cancers showing aggressive biological behavior. Although a high incidence of HPV DNA integration and a low incidence of p53 mutation were confirmed in cancer of the uterine cervix, there was no inverse association between integration of HPV types 16 and/or 18 DNA and p53 mutation.     

Frequent Occurrence of p53 Gene Mutations in Uterine Cancers at Advanced Clinical Stage and with Aggressive Histological Phenotypes

The clinical and pathological significance of mutation of the p53 tumor-suppressor gene was examined in 108 cases of primary uterine cancers using single-strand conformation polymorphism and direct DNA sequencing analyses. Mutation of the p53 gene was detected in 19 (31%) of 62 cases of cancer of the uterine corpus and was more frequent in groups at an advanced clinical stage and/or with aggressive histology. Among four adenocarcinomas arising in the lowest portion of the uterine corpus, three showed integration of human papillomavirus (HPV) types 16 and/or 18 DNA, and two of them also showed p53 mutation. In cancer of the uterine cervix, p53 mutations were rare; 1% (3/46) in total, 3% (1/30) of cases with integration of HPV types 16 and/or 18 DNA and 13% (2/16) of cases without HPV DNA integration. Three mutations were detected among two cases at clinical stage IV and two cases of undifferentiated cervical carcinoma. Immunohistochemically, all five cases of uterine cancer which showed diffuse (>50% of cancer cells) nuclear staining of p53 protein also carried the p53 mutation. Therefore, p53 alterations were suggested to be involved in the development of uterine cancers showing aggressive biological behavior. Although a high incidence of HPV DNA integration and a low incidence of pS3 mutation were confirmed in cancer of the uterine cervix, there was no inverse association between integration of HPV types 16 and/or 18 DNA and p53 mutation.     

抗癌灵治疗原发性肝癌的实验研究

 目的　观察抗癌灵水煎剂对小鼠移植性肝癌 (H2 2 )的治疗作用。方法　以瘤株 (H2 2 )接种小鼠创作模型 ,设正常对照组、荷瘤模型组及抗癌灵治疗组 ,共 3组 ,观察各组小鼠瘤重和抑瘤率、肿瘤坏死因子(TNF)的体内活性表达、各组H2 2 小鼠生命延长率以及对肝癌细胞增殖周期的影响等指标。结果　用抗癌灵治疗后的H2 2 小鼠其抑瘤率达 61 .2 0 % ,明显高于模型组 (P <0 .0 1 ) ,并能抑制荷瘤肌体TNF水平的异常表达 ,提高H2 2 荷瘤小鼠的生命延长率 ,而且该药还能阻滞肿瘤细胞周期G1期向S期进展 ,从而阻断DNA的合成和复制。结论　抗癌灵对小鼠肝癌 (H2 2 )具有明显的杀伤作用