抗人肝癌细胞膜单克隆抗体HCMP－1的制备及其生物学特性的初步鉴定

用超选择免疫法，诱导ＢＡＬＢ／ｃ小鼠对正常人肝细胞抗原产生选择性低免疫反应后，二步腹腔注射人肝癌细胞悬液，２～４周后用人肝癌细胞作强化免疫动物１次，取出脾细胞与ＳＰ２／０骨髓瘤细胞用ＰＥＧ法融合制备杂交瘤。采用细胞抗原ＥＬＩＳＡ法，同时测定培养上清对肝癌细胞及正常肝细胞的免疫反应，筛出一株能稳定分泌抗人肝癌细胞膜抗原的单克隆抗体（ＨＣＭＰ－１ＭＡｂ）的杂交瘤细胞株。ＨＣＭＰ－１ＭＡｂ是一种ＩｇＧ２ａ亚型的单抗，它与ＨＢｓＡｇ、ＨＢｃＡｇ、ＨＢｅＡｇ等乙型肝炎病毒相关抗原无交叉免疫反应，与ＡＦＰ－亦无阳性反应。免疫萤光法证实ＨＣＭＰ－１ＭＡｂ对ＱＧＹ－７７０３、ＢＥＬ－７４０２及ＳＭＭＣ－７７２１等人肝癌细胞株呈阳性反应。改良ＡＢＣ免疫组织化学证明ＨＣＭＰ－１ＭＡｂ与肝细胞癌组织呈阳性反应。说明ＨＣＭＰ－１ＭＡｂ对肝癌反应的阳性率较高，特导性较好。超选择免疫法，先联合应用免疫抑制药物使动物对正常肝细胞抗原产生低免疫反应性。再以肝癌细胞免疫时，有利于动物免疫系统对肿瘤相关抗原的识别及特异性抗体的产生。从而提高了杂交瘤制备的成功率。我们认为这一方法在单抗制备方面有较高的应用价值。     

原发性肝癌组织中Fas和FasL的表达研究

为了探讨原发性肝癌组织中乙肝病毒和丙肝病毒的感染与Ｆａｓ 和ＦａｓＬ表达的关系,采用免疫组化方法观察４０ 例原发性肝癌组织中Ｆａｓ、ＦａｓＬ、ＨＢｓＡｇ 及ＨＣＶ 抗原（ＮＳ５） 的表达。结果显示：癌细胞Ｆａｓ 阳性７ 例,阳性率为１７．５％ ,ＦａｓＬ阳性６例,阳性率为１５．０％ ;癌旁肝细胞Ｆａｓ 阳性２１ 例,阳性率５２ ．５％ ,ＦａｓＬ阳性１８ 例,阳性率４５ ．０％ 。癌组织中ＨＢｓＡｇ 阳性１２ 例,阳性率为３０．０％ ;癌旁组织中２５ 例阳性,阳性率为６２ ．５％ 。１２ 例ＨＢｓＡｇ 阳性的癌组织中,Ｆａｓ 阳性６ 例,ＦａｓＬ阳性５ 例;２８ 例ＨＢｓＡｇ 阴性的癌组织中,Ｆａｓ 和ＦａｓＬ 阳性各１ 例;癌组织中ＨＣＶＮＳ５ 阳性１１ 例,阳性率为２７ ．５ ％ ,癌旁组织中其阳性率为１２ ．５％（５／４０） ,１１ 例ＨＣＶＮＳ５ 阳性的肝癌组织中,Ｆａｓ 和ＦａｓＬ 阳性各５ 例,２９ 例ＨＣＶＮＳ５ 阴性的肝癌组织中,Ｆａｓ 阳性２ 例,ＦａｓＬ阳性１ 例。２ 组比较有显著性差异（ Ｐ＜０ ．０５） 。结果表明肝癌组织中Ｆａｓ 和ＦａｓＬ的表达与ＨＢＶ 和ＨＣＶ 的感染有一定关系。癌旁肝组织Ｆａｓ 和ＦａｓＬ高表达的意义尚不清楚     

肝癌病人血清学检测的综合探讨

检测４２例肝癌病人血清中ＡＦＰ、γ－ＧＴ、ＨＢＳＡｇ及抗－ＨＢＣ结果发现：①γ－ＧＴ在ＡＦＰ低浓度时诊断价值较大（ＡＦＰ低浓度时γ—ＧＴ的阳性率为１９％，而γ－ＧＴ低浓度时ＡＦＰ的阳性率仅为２％）。②ＨＢＳＡｇ阳性的肝癌病人其血清ＨＢＳＡｇ的效价多维持在低水平；③同一标本的ＡＦＰ与γ－ＧＴ无相关性（Ｐ＞０．０５）；④几例转移性肝癌与原发性肝癌出现了ＨＢＳＡｇ滴度与γ－ＧＴ浓度动态反常现象；⑤抗－ＨＢＣ的出现将在肝癌血清学诊断上有辅助作用（阳性率达６７％）。     

乙肝病毒和黄曲霉毒素与肝癌发生的关系

目的 探讨乙型肝炎病毒（ＨＢＶ）和黄曲霉素素（ＡＦ）与肝癌发生的关系。方法 对５６２例ＨＢｓＡｇ阳性的肝癌高危人群和７１９例ＨＢｓＡｇ阴性的对照人群进行１０年前瞻观察,同时采用抗ＡＦＭ１高亲和力的单克隆抗体系统,以免疫浓和高压液相（ＨＰＬＣ）系列测定由２５例肝癌和１２５例非肝癌对象组成的病例对照人（１：５）尿中ＡＦＭ１排出量。结果 （１）ＨＢｓＡｇｂｊ ｎｔｇ ｘｅｇ ｅｆｈ ｕｋｋｍｗ ｒｈ ｆ     

原位微环境与nm23-H1、H-rasmRNA量及肝癌肝内转移的关系

目的研究原发性肝癌原位微环境与转移相关基因ｎｍ２３－Ｈ１、Ｈ－ｒａｓｍＲＮＡ量及肝癌肝内转移的关系。方法对２５例肝细胞肝癌患者手术切除标本,采用ＲＴ－ＰＣＲ法定量检测其ｎｍ２３－Ｈ１、Ｈ－ｒａｓｍＲＮＡ量;用免疫组化方法分析微环境之重要因素微血管密度（ＭＤＶ）及癌细胞增殖情况指标－增殖细胞核抗原（ＰＣＮＡ）。结果伴肝内转移癌组织其ＭＤＶ（Ｐ＝０．００５）、ＰＣＮＡ（Ｐ＜０．０１）指标明显高于不伴肝内转移组,其ｎｍ２３－Ｈ１ｍＲＮＡ量则相反（Ｐ＜０．０１）,Ｈ－ｒａｓｍＲＮＡ量相差不显著（Ｐ＞０．０５）;ＭＤＶ与ＰＣＮＡ指数呈正相关（Ｐ＜０．０１）,ｎｍ２３Ｈ１ｍＲＮＡ量与ＰＣＮＡ指数呈负相关（Ｐ＜０．０５）。结论肝癌转移前有一明显的微环境不佳及癌细胞增生受抑制的过程。提示肝癌生长中其原位微环境不良在转移发生中起重要的选择性作用;ｎｍ２３－Ｈ１ｍＲＮＡ量可反映高转移潜能癌细胞的优势化生长情况。     

CHARACTERIZATION OF A HUMAN HERPES VIRUS－6（HHV－6） AND EPSTEIN－BARR VIRUS（EBV） ASSOCIATED LEUKEMIC CELL LINE，J6－1

ＣＨＡＲＡＣＴＥＲＩＺＡＴＩＯＮＯＦＡＨＵＭＡＮＨＥＲＰＥＳＶＩＲＵＳ－６（ＨＨＶ－６）ＡＮＤＥＰＳＴＥＩＮ－ＢＡＲＲＶＩＲＵＳ（ＥＢＶ）ＡＳＳＯＣＩＡＴＥＤＬＥＵＫＥＭＩＣＣＥＬＬＬＩＮＥ，Ｊ６－１ＷｕＫｅｆｕ吴克复；ＪａｎｏｓＬｕｋａ；Ｓｈａｎｔ...     

HBsAg阳性与阴性肝癌患者治疗前后的临床特点分析

目的：分析乙肝表面抗原（ＨＢｓＡｇ）阳性与ＨＢｓＡｇ阴性肝癌住院患者的临床特点及治疗干预对肝功能的影响。方法：对２９１例原发性肝癌患者,全部测定肝炎标志物,根据结果将患者分为ＨＢｓＡｇ阳性组及ＨＢｓＡｇ阴性组,比较两组患者的年龄、性别、甲胎蛋白（ＡＦＰ）及肝功能情况,并比较治疗前后谷丙转氨酶（ＡＬＴ）的变化。结果：原发性肝癌患者ＨＢｓＡｇ阳性２５４例（８７．３％）;ＨＢｓＡｇ阳性组ＡＦＰ阳性率７８     

EB病毒LMP1在鼻咽癌细胞系中通过TRAF2活化NF—kB

目的 为了探讨ＥＢ病毒（ＥＢＶ）中ＬＭＰ１的致瘤机制,对鼻咽癌ＬＭＰ１激活重要的核转录因子ＮＦ－ｋＢ的机制进行了研究。方法：①以ＬＭＰ１阴性的鼻咽癌细胞系ＨＮＥ２及表达载体（ｐＳＧ５）的鼻咽癌细胞系ＨＮＥ２－ｐＳＧ５为对照,采用免疫共沉淀－Ｗｅｓｔｅｒｎ－ｂｌｏｔｔｉｎｇ方法在稳定表达ＬＭＰ１的鼻咽癌细胞系ＨＮＥ２－ＬＭＰ１中证实ＬＭＰ１与ＴＲＡＦ２是否直接形成免疫共沉淀复合物;②在ＨＮＥ２－ＬＭ     

EB病毒LMP1在鼻咽癌细胞系中通过TRAF2活化NF-kB

目的：为了探讨ＥＢ病毒（ＥＢＶ）中ＬＭＰ１的致瘤机制,对鼻咽癌ＬＭＰ１激活重要的核转录因子ＮＦ－_ＫＢ的机制进行了研究。方法：①以ＬＭＰ１阴性的鼻咽癌细胞系ＨＮＥ２及表达载体（ｐＳＧ５）的鼻咽癌细胞系ＨＮＥ２－ｐＳＧＳ为对照,采用免疫共沉淀－Ｗｅｓｔｅｒｎ－ｂｌｏｔｔｉｎｇ方法在稳定表达ＬＭＰ１的鼻咽癌细胞系ＨＮＥ２－ＬＭＰ１中证实ＬＭＰ１与ＴＲＡＦ２是否直接结合形成免疫共沉淀复合物;②在ＨＮＥ２－ＬＭＰ１细胞系导入ＴＲＡＦ２表达质粒或不同剂量ＴＲＡＦ２显性负性突变体（ＴＲＡＦ２Ａ６－ ８６）表达质粒,以 ＮＦ－ｋＢ报道基因方法确定 ＬＭＰ1是否通过 ＴＲＡＦ2活化 ＮＦ－ｋＢ ;③将ＬＭＰ１（１－２３１）（ＣＴＡＲ２缺失区）或ＬＭＰ１△１８７－３５１（ＣＴＡＲＩ缺失区）及不同剂量ＴＲＡＦ２Ａ６－８６瞬时导入ＨＮＥ２中以证实ＬＭＰ１ ＣＴＡＲ１或ＣＴＡＲ２是否介导了这种效应;④以转染或未转染ＴＲＡＦ２６－８６的ＨＮＥ２－ＬＭＰ１细胞系为材料,应用免疫共沉淀－Ｗｅｓｔｅｒｎ－ｂｌｏｔｔｉｎｇ方法,确定ＴＲＡＦ２△６－８６是否竞争性抑制ＴＲＡＦ２与ＬＭＰ１结合。结果：①在ＨＮＥ２－ＬＭＰ１中ＬＭＰ１与ＴＲＡＦ２形成复合物     

老年人肝癌的临床病理特点

本文报告了老年人肝癌１６１例，结果：（１）血清ＡＰＦＰ≤３１μｇ／Ｌ者占４８．１％，显示老年肝癌患者中ＡＦＰ阴性者较多，（２）血清ＡＢｓＡｇ阳性占４６．４％，肝硬变合并率占６７．７％提示老年人肝癌的发生仍与ＨＢＶ感染有关，（３）体检发现的肝癌仅占１３％，瘤体平均直径达７．５ｃｍ，提示老年人肝癌具有隐匿快速发展的特点，（４）术后１、３、５年生存率分别为８２．６％、５９．６％和２６．１％，１１例复发性     

Differential production of angiostatin by concomitant antitumoral resistance-inducing cancer cells

HCC is a common cancer and HBV and AFB(1) are well-documented, major risk factors. Epidemiologic studies have documented that cigarette smoking also contributes to the development of HCC. PAHs are ubiquitous environmental pollutants and products of incomplete combustion. They are present in both mainstream and sidestream cigarette smoke. PAHs are metabolically activated by phase I enzymes, including CYP1A1, into electrophilic reactants (diol epoxides), which covalently bind to DNA to form adducts. Diol epoxides are also substrates for phase II detoxifying enzymes, including GSTM and GSTP. To examine the association between PAH-DNA adducts and HCC, adduct levels were determined in liver tissue by relative staining intensity with an immunoperoxidase method using a polyclonal antiserum against BPDE-modified DNA. Subjects were also genotyped for polymorphism in several genes involved in the metabolism of PAH, including GSTM1 and GSTP1. Liver tissue was collected from patients with histologically confirmed HCC (n = 105) and from non-HCC controls (n = 37). There was a significant positive correlation (r = 0.3, p < 0.01) between adducts in tumor and adjacent nontumor tissues among HCC cases. The risk of HCC was higher after adjustment for age, sex and HBsAg in the group with the highest tertile tissue levels of PAH-DNA adducts (mean relative nuclear staining intensity of tumor and nontumor tissue > 344) than in the group with the lowest tertile (staining < 241, OR = 3.9, 95% CI = 1.0-14.9). Among non-HCC controls, there were no significant associations between adduct levels and cigarette smoking, GSTM1 null genotype and HBsAg positivity. A strikingly increased HCC risk was observed (OR = 20.3, 95% CI = 5.0-81.8) among HBsAg-positive subjects whose PAH-DNA adduct levels were high (mean relative nuclear staining intensity of tumor and nontumor tissue > 301, median of control tissues) compared to HBsAg-negative subjects who had low PAH-DNA adduct levels. 4-ABP- and AFB(1)-DNA adducts had been measured previously in these same tissues. Subjects with elevated DNA adduct levels of PAH, 4-ABP and AFB(1) had a significantly higher HCC risk with an OR of 36.7 (95% CI 7.2-187.2) compared to those who had low DNA adduct levels. These results suggest that PAHs may play a role in human hepatocarcinogenesis in conjunction with HBsAg carrier status, GSTM1 and GSTP1 genotypes and exposure to 4-ABP and AFB(1).     

Genetic polymorphisms of glutathione S-transferases M1 and T1 associated with susceptibility to aflatoxin-related hepatocarcinogenesis among chronic hepatitis B carriers: a nested case-control study in Taiwan

This study was conducted to investigate the modifying effect of glutathione S-transferase (GST) M1 and T1 polymorphisms on aflatoxin-induced hepatocarcinogenesis among chronic hepatitis B virus surface antigen (HBsAg) carriers. A total of 79 HBsAg-positive cases of hepatocellular carcinoma (HCC) diagnosed between 1991 and 1997 were identified and individually matched to one or two HBsAg-positive controls on age, gender, residence and date of recruitment from the same cancer screening cohort in Taiwan. Blood samples were tested for hepatitis B and C viral markers by enzyme immunoassay and for aflatoxin B(1) (AFB(1))-albumin adducts by competitive enzyme-linked immunosorbent assay. GSTM1 and GSTT1 genotypes were determined by PCR. There was a statistically significant relationship between detectable levels of AFB(1)-albumin adducts in serum and risk of HCC among chronic HBsAg carriers, with an adjusted odds ratio (OR) of 2.0 [95% confidence interval (CI) 1.1-3.7]. In addition, the effect of aflatoxin exposure on HCC risk was more pronounced among chronic HBsAg carriers with the GSTT1 null genotype (OR 3.7, 95% CI 1.5-9.3) than those who were non-null (OR 0.9, 95% CI 0.3-2.4). The interaction between serum AFB(1)-albumin adduct level and GSTT1 genotype was statistically significant (P = 0.03). For GSTM1 the effect of aflatoxin exposure on HCC risk in those with the null genotype was also greater (adjusted OR 2.8, 95% CI 1.0-7.8) than in those with the gene present (adjusted OR 1.8, 95% CI 0.8-4.5), but the difference was not significant (P = 0.91). Notably, when the interaction between aflatoxin exposure and GSTT1 genotype was considered, aflatoxin exposure by itself was not a significant determinant of HCC risk among chronic HBsAg carriers. These results demonstrate the importance of gene-environment interactions in the multifactorial development of HCC.     

Aflatoxin B1-DNA adducts and hepatitis B virus antigens in hepatocellular carcinoma and non-tumorous liver tissue.

Studies were carried out to test the hypothesis that exposure to aflatoxin B1 (AFB1) is common among individuals with hepatocellular carcinoma (HCC) who are also chronically infected with hepatitis B virus (HBV). Experiments were also carried out to determine whether there is a close association between the presence of AFB1-DNA adducts and the expression of one or more HBV antigens in the tumor or non-tumor regions of the liver. Twenty-seven paired tumor and non-tumor liver tissues of HCC patients from Taiwan were analyzed. Monoclonal antibody 6A10, generated against the imidazole ring-opened persistent form of the major N-7 guanine adduct of AFB1, was used for adduct detection by both indirect immunofluorescence and competitive enzyme-linked immunosorbent assay. An avidin-biotin complex staining method was used for the detection of HBsAg and HBxAg in liver sections. A total of 8 (30%) HCC samples and 7 (26%) adjacent non-tumor liver tissue samples from Taiwan were positive for AFB1-DNA adducts. For HBsAg, 10 (37%) HCC samples and 22 (81%) adjacent non-tumorous liver samples were positive while 9 (33%) HCC samples and 11 (41%) adjacent non-tumor liver samples were HBxAg-positive. No association with AFB1-DNA adducts was observed for HBsAg and HBxAg. These results suggest that both AFB1 exposure and carrier status of HBsAg/HBxAg may be involved in the induction of HCC in Taiwan.     

Plasma antioxidant vitamins, chronic hepatitis B virus infection and urinary aflatoxin B1-DNA adducts in healthy males

Epidemiological evidence indicates that aflatoxin B1 (AFB1) intake is associated with an increased risk of hepatocellular carcinoma (HCC). The hepatocarcinogenesis is initiated by covalent binding of AFB1 to cellular DNA. To determine whether nutritional factors and hormonal status may influence the binding of AFB1 to hepatic DNA, a cross- sectional study was performed on a total of 42 male asymptomatic hepatitis B surface antigen (HBsAg) carriers and 43 male non-carriers in a cohort study on the multistage development of HCC in Taiwan. The major AFB1-DNA adduct in vivo, AFB1-N7-guanine, was measured by high- performance liquid chromatography in urine. Urinary AFB1-N7-guanine was detectable in 40% of the subjects. HBsAg carriers had a higher detection rate of urinary AFB1-DNA adducts than non-carriers and the difference was statistically significant after multivariate adjustment. After taking into account the total AFB1 urinary metabolite level, chronic HBsAg carrier status, and other potential confounders, plasma levels of cholesterol, alpha-tocopherol, and alpha- and beta-carotene were positively associated with the detection rate of the AFB1-DNA adducts in a dose-dependent manner, whereas plasma lycopene level was inversely related to the presence of the adducts in urine. The association of urinary AFB1-DNA adducts with the plasma levels of cholesterol, alpha-tocopherol, lycopene, and alpha- and beta-carotene was observed at both low and high exposure levels of AFB1. There was a synergistic interaction of plasma alpha-tocopherol with alpha- and beta- carotene on the adduct levels. No association with the adducts was found for plasma levels of retinol and testosterone. This study demonstrated different associations of antioxidant vitamins with AFB1- DNA adduct formation. The data consistent with our previous finding in cultured woodchuck hepatocytes that alpha-tocopherol and beta-carotene enhanced AFB1-DNA adduct formation suggest that prospective investigation of the relationship between plasma micronutrients and risk of AFB1-related HCC is warranted.      

Aflatoxin exposure and risk of hepatocellular carcinoma in Taiwan

To investigate the carcinogenic effect of environmental aflatoxin exposure, 56 cases of hepatocellular carcinoma (HCC) diagnosed between 1991 and 1995 were identified and individually matched by age, sex, residence and date of recruitment to 220 healthy controls from the same large cohort in Taiwan. Blood samples were analyzed for hepatitis B and C viral markers and for aflatoxin-albumin adducts; urine was tested for aflatoxin metabolites. We obtained information about socio-demographic characteristics, habitual alcohol drinking, cigarette smoking and diet in a structured interview. Hepatitis B virus surface antigen (HBsAg) carriers had a significantly increased risk for HCC. After adjustment for HBsAg serostatus, the matched odds ratio (OR_m) was significantly elevated for subjects with high levels of urinary aflatoxin metabolites. When stratified into tertiles, a dose-response relationship with HCC was observed. The OR_m for detectable aflatoxin-albumin adducts was not significant after adjustment for HBsAg serostatus. HBsAg-seropositive subjects with high aflatoxin exposure had a higher risk than subjects with high aflatoxin exposure only or HBsAg seropositivity only. In male HBsAg-seropositive subjects, adjusted ORs were 2.8 (95% confidence interval [Cl] = 0.9–9.1) for detectable compared with non-detectable aflatoxin-albumin adducts and 5.5 (Cl = 1.3–23.4) for high compared with low urinary aflatoxin metabolite levels. Our results suggest that environmental aflatoxin exposure may enhance the hepatic carcinogenic potential of hepatitis B virus. A large-scale study will be needed to evaluate the effect of aflatoxin exposure on HBsAg non-carriers. © 1996 Wiley-Liss, Inc.     

Association between aflatoxin B1 occupational airway exposure and risk of hepatocellular carcinoma: a case-control study

The aim of this study was to determine the airway exposure of sugar and papermaking factory workers to aflatoxin B1 (AFB1) and to explore the potential association between AFB1 airway exposure and the risk of hepatocellular carcinoma (HCC) in a case-control study. Dust samples were collected from the sugarcane bagasse warehouse, and presser and paper production workshops. Blood samples were collected from 181 workshop employees and 203 controls who worked outside the workshop. AFB1 albumin adducts were detected using a double antibody sandwich enzyme-linked immunosorbent assay (ELISA). To explore the association between AFB1 airway exposure and the risk of HCC, the medical records of 68 HCC patients who worked in a sugar and papermaking factory between January 1994 and December 2013 were analyzed. A questionnaire was used to collect information from 150 healthy controls who worked for the same company and lived near the factory. AFB1 was detected in the dust samples, but could not be detected in any of the rice samples. An analysis of serum samples revealed serum AFB1 albumin adducts in 102 (56.35 %) of the study participants. However, in the control group, only 12 (5.9 %) individuals had detectable levels of AFB1 albumin adducts. Those with airway exposure to Aspergillus flavus-contaminated dust had an elevated risk of HCC compared to those without exposure (odds ratio, 5.24; 95 % confidence interval, 2.77–9.88; P?=?0.00). The findings of this study indicate that occupational AFB1 airway exposure might be associated with the risk of AFB1-related HCC among the population that was used in this study. Intervention programs aimed at reducing exposure to inhalational AFB1 are needed urgently. Additional suitably designed, multicenter, prospective studies using large samples are needed to further confirm the results.     

Fecal and urinary excretion of aflatoxin B1 metabolites (AFQ1, AFM1 and AFB-N7-guanine) in young Chinese males

Our study was designed to assess the fecal and urinary excretion of 3 aflatoxin B1 (AFB1) metabolites, aflatoxins M1 (AFM1) and Q1 (AFQ1) and aflatoxin B1-N7-guanine (AFB-N7-guanine) that are produced by the predominant forms of cytochrome P450 enzymes responsible for the biotransformation of AFB1. Fecal and urinary AFM1, AFQ1 and urinary AFB-N7-guanine were assessed in 83 young Chinese males selected from a larger population (n = 300) based on detectable urinary AFM1. The concentration of fecal AFQ1 (median 137 ng/g fresh weight, IQR 9.1 to 450) was approximately 60 times higher than that of AFM1 (2.3 ng/g, IQR 0.0 to 7.3). In urine, the median AFQ1 was 10.4 ng/ml (IQR 3.4 to 23.3), and the median AFM1 and AFB-N7-guanine 0.04 ng/ml (IQR 0.01 to 0.33) and 0.38 ng/ml (IQR 0.0 to 2.15), respectively. A subgroup (n = 14) with hepatitis B virus (HBV) infection had significantly higher fecal concentrations of AFQ1 (p = 0.043) and AFM1 (p = 0.001) than those who were hepatitis B-virus antigen (HBsAg) negative, and the respective differences in urinary AFQ1 and AFM1 concentrations approached statistical significance (p = 0.054, p = 0.138). Our study demonstrates that AFQ1 is excreted in urine and feces at higher levels than AFM1, and feces are an important route of excretion of these AFB1 metabolites. AFQ1 should be further assessed for its predictive value as a marker for exposure and risk of dietary aflatoxins.     

HBsAg携带者黄曲霉毒素暴露与肝癌发生相关性分析

目的:研究乙型肝炎表面抗原(HBsAg)携带者黄曲霉毒素(AF)暴露与原发性肝癌(肝癌)的相关性.方法:对148例感染乙型肝炎病毒(HBV)的肝癌高危险人群进行23年前瞻观察.结果:1)AF暴露人群肝癌人年发生率为2 763.96/10万(33/1 193.94),高于非暴露人群的1 168.45/10万人年(15/1 283.75),P=0.004,RR=2.37,95％CI:1.29～4.33;其他肿瘤两组间差异无统计学意义,P=0.597.2)AF暴露人群血检丙氨酸转氨酶(ALT)异常的次数及≥2次异常的人数分别占14.38％(161/1120)及50.63％(40/1120),高于非暴露人群的9.20％(102/1 109)及33.33％(23/1109),P值分别为0.000和0.034; ALT异常人群尿中AFM;阳性率及AFM1≥10 ng例数分别为75.71％(53/70)及68.57％(48/70),高于非暴露人群的33.33％(26/78)及29.49％(23/78),P值均为0.000.3)AF暴露人群外周血中AFP阳性的次数及≥2次阳性的人数分别占6.61％(74/1120)及25.32％(20/1120),高于非暴露人群的4.15％(46/1 109)及11.59％(8/1 109),P值分别为0.010和0.033.4)HBsAg携带者HCV感染率为2.03％(3/148),个人生活史、饮酒吸烟在AF暴露与非暴露组及肝癌与非肝癌对象中差异均无统计学意义,P＞0.05.结论:AF暴露显著提高了HBV感染者的肝癌发生率,同时促进了HBV感染者肝功能损害.防治乙型肝炎和阻断AF污染是预防肝癌的有效途径.     

广西原发性肝细胞癌黄曲霉毒素B_1-DNA加合物表达及p53第249密码子突变分析

目的通过研究广西地区肝癌患者中黄曲霉毒素B1（Aflatoxin B1,AFB1）-DNA加合物的表达和p53第249密码子突变情况及其关系,探讨AFB1长期暴露与人群原发性肝细胞癌（hepatocellular carcinoma,HCC）发生的关系。方法实验组为广西医科大学第一附属医院肝胆外科收治的63例HCC患者行根治性手术切除的肝肿瘤组织。按肿瘤大小分为小肝癌组（≤5cm）和大肝癌组（〉5cm）,同时小肝癌组包括两个亚组Ⅰ组（≤3cm）和Ⅱ组（〉3cm）。另取10例来自肝移植供肝及肝外伤切除的正常肝组织作为正常对照组。通过免疫组织化学（immunohistochemistry,IHC）法检测各组样本AFB1-DNA加合物的表达,并以PCR结合直接测序的方法检测其p53第249密码子的突变情况。结果小肝癌组的AFB1-DNA加合物阳性率最高（73.8%）,显著高于大肝癌组（P=0.016）。而小肝癌组p53第249密码子的突变率（35.7%）却显著低于大肝癌组（P=0.007）。正常对照组AFB1-DNA加合物阳性率为50.0%,但未发现p53第249密码子存在突变。Ⅰ组与Ⅱ组之间无论是AFB1-DNA加合物阳性率还是p53第249密码子的突变率差异均无统计学意义（P1=0.676,P2=1.000）。实验组中,33.3%的样本为AFB1-DNA加合物和p53第249密码子突变双阳性,22.2%的样本为AFB1-DNA加合物和第249密码子突变双阴性。结论广西为AFB1高污染地区,正常人群普遍存在AFB1的暴露。AFB1的暴露可增加HCC的发病概率。p53第249密码子突变可能是影响AFB1相关HCC发生、发展的因素。结合AFB1-DNA加合物表达和第249密码子突变的情况,可有效地了解肝癌患者长期持续性或非持续性的AFB1暴露下DNA的累积损伤情况。     

Elevation of circulating immune complexes and its relationship to alpha-fetoprotein levels in patients with hepatitis B surface antigen-positive hepatocellular carcinoma.

In an attempt to evaluate the relationship between circulating immune complexes (CIC) and alpha-fetoprotein (AFP), CIC and AFP were detected in 93 hepatitis B surface antigen-positive (HBsAg+) patients with hepatocellular carcinoma (HCC) and 54 healthy controls. The median level of 3% PEG (polyethylene glycol)-CIC and Clq-CIC were higher in patients than in controls (p less than 0.001). In patients with HCC, the prevalence of elevated 3% PEG-CIC, Clq-CIC, and AFT was 27.9%, 55.9%, and 77.4%, respectively. There was association between AFP and 3% PEG-CIC positivity (p less than 0.01). The median level of 3% PEG-CIC and Clq-CIC increased as AFP levels elevated (p less than 0.05), but decreased as AFP exceeded 1599 ng/ml (p less than 0.05). For adjusting the effect of impaired liver function on the level of CIC, multivariate analysis with stepwise logistic regression revealed that 3% PEG-CIC was associated, in a dose-related fashion, with an increased risk for developing HCC (odds ratio = 1.003, p less than 0.001). These results imply that elevation of 3% PEG-CIC may be related to tumor mass. Additionally, 3% PEG-CIC is a useful marker to monitor therapy with transcatheter arterial embolization in patients with HBsAg+ HCC.